CAMIH - User contributions [en]

Howells et al. (2011): Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics

2024-08-15T08:55:19Z

CMensger:

{{Reference
|Reference=Publication: Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics
}}
{{Study Note}}
=Brief summary=
This study compared two groups of patients, all of whom had colorectal carcinoma (stage IV) with liver metastases and a life expectancy of more than 3 months. The patients received a resveratrol solution with micronized resveratrol (5.0 g) or a matching placebo once a day for approximately 14 days prior to surgical removal of the liver metastases. The purpose of the study was to assess the safety, pharmacokinetics and pharmacodynamics of the formulation (micronized resveratrol). The side effects were recorded in a daily diary according to fixed criteria. The two groups were comparable before treatment. Various side effects occurred, especially diarrhea, but the side effects were predominantly mild (grade 1). One patient discontinued the study due to diarrhea. One patient died after surgery due to peritonitis and liver failure, which, according to the study director, was not caused by resveratrol. The authors conclude that a 14-day intake of resveratrol (5.0 g) is well tolerated in colorectal cancer patients.

In dieser Studie wurden zwei Gruppen von Patienten miteinander verglichen, welche alle ein kolorektales Karzinom (Stadium IV) mit Lebermetastasen und eine Lebenserwartung von mehr als 3 Monaten hatten. Die Patienten haben ungefähr 14 Tage vor der operativen Entfernung der Lebermetastasen täglich eine Resveratrol-Lösung (5,0 g) oder ein passendes Placebo bekommen. Ziel der Studie war es, die Sicherheit, Pharmakokinetik und Pharmakodynamik der Formulierung (mikronisiertes Resveratrol) zu bewerten.Die Nebenwirkungen wurden mittels täglicher Tagebuchführung nach festen Kriterien erhoben. Die beiden Gruppen waren vor der Behandlung vergleichbar. Es traten verschiedene Nebenwirkungen v.a. Durchfall auf, allerdings waren die Nebenwirkungen überwiegend mild ausgeprägt (Grad 1). Ein Patient brach die Studie wegen Durchfall ab. Ein Patient starb nach der OP an einer Bauchfellentzündung und Leberversagen, was aber laut des Studienleiters nicht durch Resveratrol verursacht war. Die Autoren schließen, dass eine 14 tägige Einnahme von Resveratrol (5,0 g) bei Darmkrebspatienten gut verträglich ist.

=Study Design=

{{Study Design (RCT)
|Perspective=Prospective
|Centralized=Multicentric
|Blinding=Double
|Is randomized=Yes
|Cross-over=No
|Number of arms=2
}}
=Study characteristics=

{{RCT study general properties
|Inclusion criteria=Subjects (18 years or older) presenting with confirmed stage IV colorectal cancer and hepatic metastases, who had not received therapeutic intervention for their cancer within 6 weeks of study commencement and had a life expectancy of >3 months, were recruited into the study. All patients were due to undergo resection of liver metastases. Participants had to be physically capable of complying with the protocol and had a normal ECG and no history of HIV or hepatitis B/C.
|Exclusion criteria=Patient were asked to refrain from large quantities of resveratrol-containing foods and drinks such as peanuts, grapes, mulberries and alcohol within 48 h of scheduled PK collection days, and the day of surgical resection.
|N randomized=9
|Analysis=?
|Specifications on analyses=All nine subjects were analysed. This is a Phase I study about safety, pharmapharmacokinetics, pharmacodynamics and not an efficacy study.
PK: Statistical analyses for pharmacokinetic data included linear regression with 1/concentration weighting and descriptive statistics.
PD: Means were compared via one way, one sided ANOVA followed by Tukey’s post hoc test.
|Countries of data collection=United Kingdom
|LoE=2b Oxford 2009
|Outcome timeline=Patients ingested the formulation pre-operatively daily for a minimum of 10 and a maximum of 21 days, dependent upon surgical scheduling. Plasma samples for PK assessment were obtained on days 1 and 2, and on the day of surgical resection. Plasma for PD assessment was obtained pre-dose, immediately prior to, and during surgery. Diseased and normal adjacent hepatic tissue was resected 6-7 h after the last dose.
}}
=Characteristics of participants=

{{Characteristics of participants
|Setting=Palliative
|Types of cancer=Colorectal Cancer
|Stage cancer=Advanced Stage
|Cancer stage specification=Stage IV colorectal cancer and hepatic metastases
|Comorbidity=NI
|Current cancer therapy=Surgery
|Specifications on cancer therapies=Resection of liver metastases
|Previous cancer therapies=NI
|Gender=Mixed
|Gender specifications=SRT501 (resveratrol): Male (5), female (1)
Placebo: Male (1), female (2)
|Age groups=Adults (18+)
|Age groups specification=SRT501 (resveratrol): 68.5(10.8) years
Placebo: 64.3(6.35) years
}}
=Arms=

{{Arm
|Arm type=Intervention
|Number of participants (arm)=6
|Drop-out=0
|Drop-out reasons=NA
|Intervention=Resveratrol
|Dosage and regime=Oral (suspension) of microparticular resveratrol (SRT501): 1 x 5,0 g daily for approximately 14 days (minimum of 10 and a maximum of 21 days before surgery)
|One-time application=No
|Duration in days=14
|Side Effects / Interactions=AEs possibly or probably attributable to agent intake: They were primarily of a gastrointestinal nature, including nausea and diarrhoea, and mild in grade (grade 1 NCI CTC v3.0). Other AEs included chills, lethargy, rash, skin irritation and vascular flushing, which resolved without sequelae.
|Order number=1
}}
{{Arm
|Arm type=Placebo
|Number of participants (arm)=3
|Drop-out=0
|Drop-out reasons=NA
|Intervention=Placebo
|Dosage and regime=Oral (suspension) of placebo 1 x daily for approximately 14 days (minimum of 10 and a maximum of 21 days before surgery)
|One-time application=No
|Duration in days=14
|Side Effects / Interactions=One case of lethargy in the placebo group, which was ongoing at follow-up. One case with diarrhoea.
|Order number=2
}}
{{Arm Overview}}
=Outcomes=

{{Outcome
|Outcome type=Others
|Outcome name=PK (Pharmacokinetics)
|Outcome specification=Resveratrol pharmacokinetics in blood (1) and concentration in liver tissue (2):
(1) Patients’ plasma was analysed by HPLC-MS/MS for resveratrol.
(2) Resveratrol was quantified in tumor and normal adjacent hepatic tissues.
|Type of measurement=Blood Test, Histological examination
|Results during intervention=NA
|Results after intervention=Overall:
(1) Blood: Resveratrol concentrations were below the lower limits of quantitation (LLOQ) for all samples from subjects receiving placebo, and measurable in patients who received SRT501. Cmax levels were reached 2.8 h post-dose, and the mean maximum plasma concentration was 1942 ng/mL (8.51 nmol/mL). The mean plasma elimination half-life was just over 1h.

(2) Tissue: Levels of resveratrol were below the LLOQ in all subjects on placebo and one of the six patients on SRT501. Mean resveratrol levels in the remaining five patients receiving SRT501 were 1098±1393 ng/g (4.81 nmol/g, range 52-2834 ng/g) and 420±341 ng/g (1.84 nmol/g, range 46-914 ng/g) in tumor and normal tissue, respectively.
|Bias arising from the randomization process=?
|Bias due to deviation from intended intervention (assignment to intervention)=?
|Bias due to deviation from intended intervention (adhering to intervention)=NA
|Bias due to missing outcome data=?
|Bias in measurement of the outcome=?
|Bias in selection of the reported result=?
|Other sources of bias=?
|Overall RoB judgment=?
|Order number=1
}}
{{Outcome
|Outcome type=Others
|Outcome name=PD (Pharmacodynamics)
|Outcome specification=Potential effects of SRT501 on processes relevant to cell survival and apoptosis were measured in plasma and tissue.
|Type of measurement=Blood Test, Histological examination
|Results during intervention=NA
|Results after intervention=Overall:
There was no difference between patients who received placebo or SRT501 in terms of plasma/serum levels of prostaglandin E2 (PGE-2) and vascular endothelial growth factor (VEGF). The analysed tissue samples show no significant differences between placebo and SRT501. Apoptosis, as reflected by immunohistochemistry for cleaved caspase 3 in tumor tissue, was significantly increased by 39% (to 1.44% total apoptotic cells, p=0.038) in patients on SRT501 compared to those taking placebo.
|Bias arising from the randomization process=?
|Bias due to deviation from intended intervention (assignment to intervention)=?
|Bias due to deviation from intended intervention (adhering to intervention)=NA
|Bias due to missing outcome data=?
|Bias in measurement of the outcome=?
|Bias in selection of the reported result=?
|Other sources of bias=?
|Overall RoB judgment=?
|Order number=2
}}
{{Outcome Overview}}
=Funding and Conflicts of Interest=

{{Funding and Conflicts of Interest
|Funding=Study was designed and sponsored by Sirtris
|Conflicts of Interest=According to authors no conflict of interest.
}}
=Further points for assessing the study=
As this is a Phase I study, this section is not applicable. This assessment was designed for efficacy studies.

{{Further points for assessing the study
|Samples sufficiently large=?
|power analysis performed=?
|reasons given for samples being too small according to power analysis=?
|Ethnicity mentioned=Yes
|Possibility of attention effects=NA
|Possibility of placebo effects=NA
|Other reasons=?
|Testing for normal distribution=NA
|Correct application of statistical tests=?
|Correction for multiple testing=NA
|Measurement of compliance=NA
|Blinding reliable=NA
|Check whether blinding was successful=NA
|Consistent reporting in numbers=?
|sufficient washout period=NA
|Tested for carry-over effects=NA
|Were sequence effects tested=NA
|Comprehensive and coherent reporting=?
|Were side effects systematically recorded=NA
|Effect sizes reported=NA
|Side effects taken into account in the interpretation of the results=NA
|mono- or multicentric=NA
|Ethics / CoI / Funding=Study was funded by Sirtris.
}}
{{Additional Notes}}
=Additional Notes=

Howells et al. (2011): Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics

2024-08-08T11:05:30Z

CMensger:

{{Reference
|Reference=Publication: Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics
}}
{{Study Note}}
=Brief summary=
This study compared two groups of patients, all of whom had colorectal carcinoma (stage IV) with liver metastases and a life expectancy of more than 3 months. The patients received a resveratrol solution with micronized resveratrol (5.0 g) or a matching placebo once a day for approximately 14 days prior to surgical removal of the liver metastases. The purpose of the study was to assess the safety, pharmacokinetics and pharmacodynamics of the formulation (micronized resveratrol). The side effects were recorded in a daily diary according to fixed criteria. The two groups were comparable before treatment. Various side effects occurred, especially diarrhea, but the side effects were predominantly mild (grade 1). One patient discontinued the study due to diarrhea. One patient died after surgery due to peritonitis and liver failure, which, according to the study director, was not caused by resveratrol. The authors conclude that a 14-day intake of resveratrol (5.0 g) is well tolerated in colorectal cancer patients.

In dieser Studie wurden zwei Gruppen von Patienten miteinander verglichen, welche alle ein kolorektales Karzinom (Stadium IV) mit Lebermetastasen und eine Lebenserwartung von mehr als 3 Monaten hatten. Die Patienten haben ungefähr 14 Tage vor der operativen Entfernung der Lebermetastasen täglich eine Resveratrol-Lösung (5,0 g) oder ein passendes Placebo bekommen. Ziel der Studie war es, die Sicherheit, Pharmakokinetik und Pharmakodynamik der Formulierung (mikronisiertes Resveratrol) zu bewerten.Die Nebenwirkungen wurden mittels täglicher Tagebuchführung nach festen Kriterien erhoben. Die beiden Gruppen waren vor der Behandlung vergleichbar. Es traten verschiedene Nebenwirkungen v.a. Durchfall auf, allerdings waren die Nebenwirkungen überwiegend mild ausgeprägt (Grad 1). Ein Patient brach die Studie wegen Durchfall ab. Ein Patient starb nach der OP an einer Bauchfellentzündung und Leberversagen, was aber laut des Studienleiters nicht durch Resveratrol verursacht war. Die Autoren schließen, dass eine 14 tägige Einnahme von Resveratrol (5,0 g) bei Darmkrebspatienten gut verträglich ist.

=Study Design=

{{Study Design (RCT)
|Perspective=Prospective
|Centralized=Multicentric
|Blinding=Double
|Is randomized=Yes
|Cross-over=No
|Number of arms=2
}}
=Study characteristics=

{{RCT study general properties
|Inclusion criteria=Subjects (18 years or older) presenting with confirmed stage IV colorectal cancer and hepatic metastases, who had not received therapeutic intervention for their cancer within 6 weeks of study commencement and had a life expectancy of >3 months, were recruited into the study. All patients were due to undergo resection of liver metastases. Participants had to be physically capable of complying with the protocol and had a normal ECG and no history of HIV or hepatitis B/C.
|Exclusion criteria=Patient were asked to refrain from large quantities of resveratrol-containing foods and drinks such as peanuts, grapes, mulberries and alcohol within 48 h of scheduled PK collection days, and the day of surgical resection.
|N randomized=9
|Analysis=?
|Specifications on analyses=All nine subjects were analysed. This is a Phase I study about safety, pharmapharmacokinetics, pharmacodynamics and not an efficacy study.
PK: Statistical analyses for pharmacokinetic data included linear regression with 1/concentration weighting and descriptive statistics.
PD: Means were compared via one way, one sided ANOVA followed by Tukey’s post hoc test.
|Countries of data collection=United Kingdom
|LoE=2b Oxford 2009
|Outcome timeline=Patients ingested the formulation pre-operatively daily for a minimum of 10 and a maximum of 21 days, dependent upon surgical scheduling. Plasma samples for PK assessment were obtained on days 1 and 2, and on the day of surgical resection. Plasma for PD assessment was obtained pre-dose, immediately prior to, and during surgery. Diseased and normal adjacent hepatic tissue was resected 6-7 h after the last dose.
}}
=Characteristics of participants=

{{Characteristics of participants
|Setting=Palliative
|Types of cancer=Colorectal Cancer
|Stage cancer=Advanced Stage
|Cancer stage specification=Stage IV colorectal cancer and hepatic metastases
|Comorbidity=NI
|Current cancer therapy=Surgery
|Specifications on cancer therapies=Resection of liver metastases
|Previous cancer therapies=NI
|Gender=Mixed
|Gender specifications=SRT501 (resveratrol): Male (5), female (1)
Placebo: Male (1), female (2)
|Age groups=Adults (18+)
|Age groups specification=SRT501 (resveratrol): 68.5(10.8) years
Placebo: 64.3(6.35) years
}}
=Arms=

{{Arm
|Arm type=Intervention
|Number of participants (arm)=6
|Drop-out=0
|Drop-out reasons=NA
|Intervention=Resveratrol
|Dosage and regime=Oral (suspension) of microparticular resveratrol (SRT501): 1 x 5,0 g daily for approximately 14 days (minimum of 10 and a maximum of 21 days before surgery)
|One-time application=No
|Duration in days=14
|Side Effects / Interactions=AEs possibly or probably attributable to agent intake: They were primarily of a gastrointestinal nature, including nausea and diarrhoea, and mild in grade (grade 1 NCI CTC v3.0). Other AEs included chills, lethargy, rash, skin irritation and vascular flushing, which resolved without sequelae.
|Order number=1
}}
{{Arm
|Arm type=Placebo
|Number of participants (arm)=3
|Drop-out=0
|Drop-out reasons=NA
|Intervention=Placebo
|Dosage and regime=Oral (suspension) of placebo 1 x daily for approximately 14 days (minimum of 10 and a maximum of 21 days before surgery)
|One-time application=No
|Duration in days=14
|Side Effects / Interactions=One case of lethargy in the placebo group, which was ongoing at follow-up. One case with diarrhoea.
|Order number=2
}}
{{Arm Overview}}
=Outcomes=

{{Outcome
|Outcome type=Others
|Outcome name=PK (Pharmacokinetics)
|Outcome specification=Resveratrol pharmacokinetics in blood (1) and concentration in liver tissue (2):
(1) Patients’ plasma was analysed by HPLC-MS/MS for resveratrol.
(2) Resveratrol was quantified in tumor and normal adjacent hepatic tissues.
|Type of measurement=Blood Test, Histological examination
|Results during intervention=NA
|Results after intervention=Overall:
(1) Blood: Resveratrol concentrations were below the lower limits of quantitation (LLOQ) for all samples from subjects receiving placebo, and measurable in patients who received SRT501. Cmax levels were reached 2.8 h post-dose, and the mean maximum plasma concentration was 1942 ng/mL (8.51 nmol/mL). The mean plasma elimination half-life was just over 1h.

(2) Tissue: Levels of resveratrol were below the LLOQ in all subjects on placebo and one of the six patients on SRT501. Mean resveratrol levels in the remaining five patients receiving SRT501 were 1098±1393 ng/g (4.81 nmol/g, range 52-2834 ng/g) and 420±341 ng/g (1.84 nmol/g, range 46-914 ng/g) in tumor and normal tissue, respectively.
|Bias arising from the randomization process=?
|Bias due to deviation from intended intervention (assignment to intervention)=?
|Bias due to deviation from intended intervention (adhering to intervention)=NA
|Bias due to missing outcome data=?
|Bias in measurement of the outcome=?
|Bias in selection of the reported result=?
|Other sources of bias=?
|Overall RoB judgment=?
|Order number=2
}}
{{Outcome
|Outcome type=Others
|Outcome name=PD (Pharmacodynamics)
|Outcome specification=Potential effects of SRT501 on processes relevant to cell survival and apoptosis were measured in plasma and tissue.
|Type of measurement=Blood Test, Histological examination
|Results during intervention=NA
|Results after intervention=Overall:
There was no difference between patients who received placebo or SRT501 in terms of plasma/serum levels of prostaglandin E2 (PGE-2) and vascular endothelial growth factor (VEGF). The analysed tissue samples show no significant differences between placebo and SRT501. Apoptosis, as reflected by immunohistochemistry for cleaved caspase 3 in tumor tissue, was significantly increased by 39% (to 1.44% total apoptotic cells, p=0.038) in patients on SRT501 compared to those taking placebo.
|Bias arising from the randomization process=?
|Bias due to deviation from intended intervention (assignment to intervention)=?
|Bias due to deviation from intended intervention (adhering to intervention)=NA
|Bias due to missing outcome data=?
|Bias in measurement of the outcome=?
|Bias in selection of the reported result=?
|Other sources of bias=?
|Overall RoB judgment=?
|Order number=3
}}
{{Outcome
|Outcome type=?
|Outcome name=?
|Outcome specification=?
|Type of measurement=?
|Results during intervention=?
|Results after intervention=?
|Bias arising from the randomization process=?
|Bias due to deviation from intended intervention (assignment to intervention)=?
|Bias due to deviation from intended intervention (adhering to intervention)=NA
|Bias due to missing outcome data=?
|Bias in measurement of the outcome=?
|Bias in selection of the reported result=?
|Other sources of bias=?
|Overall RoB judgment=?
|Order number=3
}}
{{Outcome Overview}}
=Funding and Conflicts of Interest=

{{Funding and Conflicts of Interest
|Funding=Study was designed and sponsored by Sirtris
|Conflicts of Interest=According to authors no conflict of interest.
}}
=Further points for assessing the study=
As this is a Phase I study, this section is not applicable. This assessment was designed for efficacy studies.

{{Further points for assessing the study
|Samples sufficiently large=?
|power analysis performed=?
|reasons given for samples being too small according to power analysis=?
|Ethnicity mentioned=Yes
|Possibility of attention effects=NA
|Possibility of placebo effects=NA
|Other reasons=?
|Testing for normal distribution=NA
|Correct application of statistical tests=?
|Correction for multiple testing=NA
|Measurement of compliance=NA
|Blinding reliable=NA
|Check whether blinding was successful=NA
|Consistent reporting in numbers=?
|sufficient washout period=NA
|Tested for carry-over effects=NA
|Were sequence effects tested=NA
|Comprehensive and coherent reporting=?
|Were side effects systematically recorded=NA
|Effect sizes reported=NA
|Side effects taken into account in the interpretation of the results=NA
|mono- or multicentric=NA
|Ethics / CoI / Funding=Study was funded by Sirtris.
}}
{{Additional Notes}}
=Additional Notes=

Howells et al. (2011): Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics

2024-08-08T10:56:54Z

CMensger:

{{Reference
|Reference=Publication: Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics
}}
{{Study Note}}
=Brief summary=
This study compared two groups of patients, all of whom had colorectal carcinoma (stage IV) with liver metastases and a life expectancy of more than 3 months. The patients received a resveratrol solution with micronized resveratrol (5.0 g) or a matching placebo once a day for approximately 14 days prior to surgical removal of the liver metastases. The purpose of the study was to assess the safety, pharmacokinetics and pharmacodynamics of the formulation (micronized resveratrol). The side effects were recorded in a daily diary according to fixed criteria. The two groups were comparable before treatment. Various side effects occurred, especially diarrhea, but the side effects were predominantly mild (grade 1). One patient discontinued the study due to diarrhea. One patient died after surgery due to peritonitis and liver failure, which, according to the study director, was not caused by resveratrol. The authors conclude that a 14-day intake of resveratrol (5.0 g) is well tolerated in colorectal cancer patients.

In dieser Studie wurden zwei Gruppen von Patienten miteinander verglichen, welche alle ein kolorektales Karzinom (Stadium IV) mit Lebermetastasen und eine Lebenserwartung von mehr als 3 Monaten hatten. Die Patienten haben ungefähr 14 Tage vor der operativen Entfernung der Lebermetastasen täglich eine Resveratrol-Lösung (5,0 g) oder ein passendes Placebo bekommen. Ziel der Studie war es, die Sicherheit, Pharmakokinetik und Pharmakodynamik der Formulierung (mikronisiertes Resveratrol) zu bewerten.Die Nebenwirkungen wurden mittels täglicher Tagebuchführung nach festen Kriterien erhoben. Die beiden Gruppen waren vor der Behandlung vergleichbar. Es traten verschiedene Nebenwirkungen v.a. Durchfall auf, allerdings waren die Nebenwirkungen überwiegend mild ausgeprägt (Grad 1). Ein Patient brach die Studie wegen Durchfall ab. Ein Patient starb nach der OP an einer Bauchfellentzündung und Leberversagen, was aber laut des Studienleiters nicht durch Resveratrol verursacht war. Die Autoren schließen, dass eine 14 tägige Einnahme von Resveratrol (5,0 g) bei Darmkrebspatienten gut verträglich ist.

=Study Design=

{{Study Design (RCT)
|Perspective=Prospective
|Centralized=Multicentric
|Blinding=Double
|Is randomized=Yes
|Cross-over=No
|Number of arms=2
}}
=Study characteristics=

{{RCT study general properties
|Inclusion criteria=Subjects (18 years or older) presenting with confirmed stage IV colorectal cancer and hepatic metastases, who had not received therapeutic intervention for their cancer within 6 weeks of study commencement and had a life expectancy of >3 months, were recruited into the study. All patients were due to undergo resection of liver metastases. Participants had to be physically capable of complying with the protocol and had a normal ECG and no history of HIV or hepatitis B/C.
|Exclusion criteria=Patient were asked to refrain from large quantities of resveratrol-containing foods and drinks such as peanuts, grapes, mulberries and alcohol within 48 h of scheduled PK collection days, and the day of surgical resection.
|N randomized=9
|Analysis=?
|Specifications on analyses=All nine subjects were analysed. This is a Phase I study about safety, pharmapharmacokinetics, pharmacodynamics and not an efficacy study.
PK: Statistical analyses for pharmacokinetic data included linear regression with 1/concentration weighting and descriptive statistics.
PD: Means were compared via one way, one sided ANOVA followed by Tukey’s post hoc test.
|Countries of data collection=United Kingdom
|LoE=2b Oxford 2009
|Outcome timeline=Patients ingested the formulation pre-operatively daily for a minimum of 10 and a maximum of 21 days, dependent upon surgical scheduling. Plasma samples for PK assessment were obtained on days 1 and 2, and on the day of surgical resection. Plasma for PD assessment was obtained pre-dose, immediately prior to, and during surgery. Diseased and normal adjacent hepatic tissue was resected 6-7 h after the last dose.
}}
=Characteristics of participants=

{{Characteristics of participants
|Setting=Palliative
|Types of cancer=Colorectal Cancer
|Stage cancer=Advanced Stage
|Cancer stage specification=Stage IV colorectal cancer and hepatic metastases
|Comorbidity=NI
|Current cancer therapy=Surgery
|Specifications on cancer therapies=Resection of liver metastases
|Previous cancer therapies=NI
|Gender=Mixed
|Gender specifications=SRT501 (resveratrol): Male (5), female (1)
Placebo: Male (1), female (2)
|Age groups=Adults (18+)
|Age groups specification=SRT501 (resveratrol): 68.5(10.8) years
Placebo: 64.3(6.35) years
}}
=Arms=

{{Arm
|Arm type=Intervention
|Number of participants (arm)=6
|Drop-out=0
|Drop-out reasons=NA
|Intervention=Resveratrol
|Dosage and regime=Oral (suspension) of microparticular resveratrol (SRT501): 1 x 5,0 g daily for approximately 14 days (minimum of 10 and a maximum of 21 days before surgery)
|One-time application=No
|Duration in days=14
|Side Effects / Interactions=AEs possibly or probably attributable to agent intake: They were primarily of a gastrointestinal nature, including nausea and diarrhoea, and mild in grade (grade 1 NCI CTC v3.0). Other AEs included chills, lethargy, rash, skin irritation and vascular flushing, which resolved without sequelae.
|Order number=1
}}
{{Arm
|Arm type=Placebo
|Number of participants (arm)=3
|Drop-out=0
|Drop-out reasons=NA
|Intervention=Placebo
|Dosage and regime=Oral (suspension) of placebo 1 x daily for approximately 14 days (minimum of 10 and a maximum of 21 days before surgery)
|One-time application=No
|Duration in days=14
|Side Effects / Interactions=One case of lethargy in the placebo group, which was ongoing at follow-up. One case with diarrhoea.
|Order number=2
}}
{{Arm Overview}}
=Outcomes=

{{Outcome
|Outcome type=Others
|Outcome name=PK (Pharmacokinetics)
|Outcome specification=Resveratrol pharmacokinetics in blood (1) and concentration in liver tissue (2):
(1) Patients’ plasma was analysed by HPLC-MS/MS for resveratrol.
(2) Resveratrol was quantified in tumor and normal adjacent hepatic tissues.
|Type of measurement=Blood Test, Histological examination
|Results during intervention=NA
|Results after intervention=Overall:
(1) Blood: Resveratrol concentrations were below the lower limits of quantitation (LLOQ) for all samples from subjects receiving placebo, and measurable in patients who received SRT501. Cmax levels were reached 2.8 h post-dose, and the mean maximum plasma concentration was 1942 ng/mL (8.51 nmol/mL). The mean plasma elimination half-life was just over 1h.

(2) Tissue: Levels of resveratrol were below the LLOQ in all subjects on placebo and one of the six patients on SRT501. Mean resveratrol levels in the remaining five patients receiving SRT501 were 1098±1393 ng/g (4.81 nmol/g, range 52-2834 ng/g) and 420±341 ng/g (1.84 nmol/g, range 46-914 ng/g) in tumor and normal tissue, respectively.
|Bias arising from the randomization process=?
|Bias due to deviation from intended intervention (assignment to intervention)=?
|Bias due to deviation from intended intervention (adhering to intervention)=NA
|Bias due to missing outcome data=?
|Bias in measurement of the outcome=?
|Bias in selection of the reported result=?
|Other sources of bias=?
|Overall RoB judgment=?
|Order number=2
}}
{{Outcome
|Outcome type=Others
|Outcome name=PD (Pharmacodynamics)
|Outcome specification=Potential effects of SRT501 on processes relevant to cell survival and apoptosis were measured in plasma and tissue.
|Type of measurement=Blood Test, Histological examination
|Results during intervention=NA
|Results after intervention=Overall:
There was no difference between patients who received placebo or SRT501 in terms of plasma/serum levels of prostaglandin E2 (PGE-2) and vascular endothelial growth factor (VEGF). The analysed tissue samples show no significant differences between placebo and SRT501. Apoptosis, as reflected by immunohistochemistry for cleaved caspase 3 in tumor tissue, was significantly increased by 39% (to 1.44% total apoptotic cells, p=0.038) in patients on SRT501 compared to those taking placebo.
|Bias arising from the randomization process=?
|Bias due to deviation from intended intervention (assignment to intervention)=?
|Bias due to deviation from intended intervention (adhering to intervention)=NA
|Bias due to missing outcome data=?
|Bias in measurement of the outcome=?
|Bias in selection of the reported result=?
|Other sources of bias=?
|Overall RoB judgment=?
|Order number=3
}}
{{Outcome
|Outcome type=?
|Outcome name=?
|Outcome specification=?
|Type of measurement=?
|Results during intervention=?
|Results after intervention=?
|Bias arising from the randomization process=?
|Bias due to deviation from intended intervention (assignment to intervention)=?
|Bias due to deviation from intended intervention (adhering to intervention)=NA
|Bias due to missing outcome data=?
|Bias in measurement of the outcome=?
|Bias in selection of the reported result=?
|Other sources of bias=?
|Overall RoB judgment=?
|Order number=1
}}
{{Outcome Overview}}
=Funding and Conflicts of Interest=

{{Funding and Conflicts of Interest
|Funding=Study was designed and sponsored by Sirtris
|Conflicts of Interest=According to authors no conflict of interest.
}}
=Further points for assessing the study=

{{Further points for assessing the study
|Samples sufficiently large=No
|power analysis performed=?
|reasons given for samples being too small according to power analysis=?
|Ethnicity mentioned=Yes
|Possibility of attention effects=NA
|Possibility of placebo effects=NA
|Other reasons=?
|Testing for normal distribution=?
|Correct application of statistical tests=?
|Correction for multiple testing=?
|Measurement of compliance=?
|Blinding reliable=?
|Check whether blinding was successful=?
|Consistent reporting in numbers=?
|sufficient washout period=?
|Tested for carry-over effects=?
|Were sequence effects tested=?
|Comprehensive and coherent reporting=?
|Were side effects systematically recorded=?
|Effect sizes reported=?
|Side effects taken into account in the interpretation of the results=?
|mono- or multicentric=?
|Ethics / CoI / Funding=?
}}
{{Additional Notes}}
=Additional Notes=

Howells et al. (2011): Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics

2024-08-08T10:45:31Z

CMensger:

{{Reference
|Reference=Publication: Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics
}}
{{Study Note}}
=Brief summary=
This study compared two groups of patients, all of whom had colorectal carcinoma (stage IV) with liver metastases and a life expectancy of more than 3 months. The patients received a resveratrol solution with micronized resveratrol (5.0 g) or a matching placebo once a day for approximately 14 days prior to surgical removal of the liver metastases. The purpose of the study was to assess the safety, pharmacokinetics and pharmacodynamics of the formulation (micronized resveratrol). The side effects were recorded in a daily diary according to fixed criteria. The two groups were comparable before treatment. Various side effects occurred, especially diarrhea, but the side effects were predominantly mild (grade 1). One patient discontinued the study due to diarrhea. One patient died after surgery due to peritonitis and liver failure, which, according to the study director, was not caused by resveratrol. The authors conclude that a 14-day intake of resveratrol (5.0 g) is well tolerated in colorectal cancer patients.

In dieser Studie wurden zwei Gruppen von Patienten miteinander verglichen, welche alle ein kolorektales Karzinom (Stadium IV) mit Lebermetastasen und eine Lebenserwartung von mehr als 3 Monaten hatten. Die Patienten haben ungefähr 14 Tage vor der operativen Entfernung der Lebermetastasen täglich eine Resveratrol-Lösung (5,0 g) oder ein passendes Placebo bekommen. Ziel der Studie war es, die Sicherheit, Pharmakokinetik und Pharmakodynamik der Formulierung (mikronisiertes Resveratrol) zu bewerten.Die Nebenwirkungen wurden mittels täglicher Tagebuchführung nach festen Kriterien erhoben. Die beiden Gruppen waren vor der Behandlung vergleichbar. Es traten verschiedene Nebenwirkungen v.a. Durchfall auf, allerdings waren die Nebenwirkungen überwiegend mild ausgeprägt (Grad 1). Ein Patient brach die Studie wegen Durchfall ab. Ein Patient starb nach der OP an einer Bauchfellentzündung und Leberversagen, was aber laut des Studienleiters nicht durch Resveratrol verursacht war. Die Autoren schließen, dass eine 14 tägige Einnahme von Resveratrol (5,0 g) bei Darmkrebspatienten gut verträglich ist.

=Study Design=

{{Study Design (RCT)
|Perspective=Prospective
|Centralized=Multicentric
|Blinding=Double
|Is randomized=Yes
|Cross-over=No
|Number of arms=2
}}
=Study characteristics=

{{RCT study general properties
|Inclusion criteria=Subjects (18 years or older) presenting with confirmed stage IV colorectal cancer and hepatic metastases, who had not received therapeutic intervention for their cancer within 6 weeks of study commencement and had a life expectancy of >3 months, were recruited into the study. All patients were due to undergo resection of liver metastases. Participants had to be physically capable of complying with the protocol and had a normal ECG and no history of HIV or hepatitis B/C.
|Exclusion criteria=Patient were asked to refrain from large quantities of resveratrol-containing foods and drinks such as peanuts, grapes, mulberries and alcohol within 48 h of scheduled PK collection days, and the day of surgical resection.
|N randomized=9
|Analysis=?
|Specifications on analyses=All nine subjects were analysed. This is a Phase I study about safety, pharmapharmacokinetics, pharmacodynamics and not an efficacy study.
PK: Statistical analyses for pharmacokinetic data included linear regression with 1/concentration weighting and descriptive statistics.
PD: Means were compared via one way, one sided ANOVA followed by Tukey’s post hoc test.
|Countries of data collection=United Kingdom
|LoE=2b Oxford 2009
|Outcome timeline=Patients ingested the formulation pre-operatively daily for a minimum of 10 and a maximum of 21 days, dependent upon surgical scheduling. Plasma samples for PK assessment were obtained on days 1 and 2, and on the day of surgical resection. Plasma for PD assessment was obtained pre-dose, immediately prior to, and during surgery. Diseased and normal adjacent hepatic tissue was resected 6-7 h after the last dose.
}}
=Characteristics of participants=

{{Characteristics of participants
|Setting=Palliative
|Types of cancer=Colorectal Cancer
|Stage cancer=Advanced Stage
|Cancer stage specification=Stage IV colorectal cancer and hepatic metastases
|Comorbidity=NI
|Current cancer therapy=Surgery
|Specifications on cancer therapies=Resection of liver metastases
|Previous cancer therapies=NI
|Gender=Mixed
|Gender specifications=SRT501 (resveratrol): Male (5), female (1)
Placebo: Male (1), female (2)
|Age groups=Adults (18+)
|Age groups specification=SRT501 (resveratrol): 68.5(10.8) years
Placebo: 64.3(6.35) years
}}
=Arms=

{{Arm
|Arm type=Intervention
|Number of participants (arm)=6
|Drop-out=0
|Drop-out reasons=NA
|Intervention=Resveratrol
|Dosage and regime=Oral (suspension) of microparticular resveratrol (SRT501): 1 x 5,0 g daily for approximately 14 days (minimum of 10 and a maximum of 21 days before surgery)
|One-time application=No
|Duration in days=14
|Side Effects / Interactions=AEs possibly or probably attributable to agent intake: They were primarily of a gastrointestinal nature, including nausea and diarrhoea, and mild in grade (grade 1 NCI CTC v3.0). Other AEs included chills, lethargy, rash, skin irritation and vascular flushing, which resolved without sequelae.
|Order number=1
}}
{{Arm
|Arm type=Placebo
|Number of participants (arm)=3
|Drop-out=0
|Drop-out reasons=NA
|Intervention=Placebo
|Dosage and regime=Oral (suspension) of placebo 1 x daily for approximately 14 days (minimum of 10 and a maximum of 21 days before surgery)
|One-time application=No
|Duration in days=14
|Side Effects / Interactions=One case of lethargy in the placebo group, which was ongoing at follow-up. One case with diarrhoea.
|Order number=2
}}
{{Arm Overview}}
=Outcomes=

{{Outcome
|Outcome type=Others
|Outcome name=PK (Pharmacokinetics)
|Outcome specification=Resveratrol pharmacokinetics in blood (1) and concentration in liver tissue (2):
(1) Patients’ plasma was analysed by HPLC-MS/MS for resveratrol.
(2) Resveratrol was quantified in tumor and normal adjacent hepatic tissues.
|Type of measurement=Blood Test, Histological examination
|Results during intervention=NA
|Results after intervention=Overall:
(1) Blood: Resveratrol concentrations were below the lower limits of quantitation (LLOQ) for all samples from subjects receiving placebo, and measurable in patients who received SRT501. Cmax levels were reached 2.8 h post-dose, and the mean maximum plasma concentration was 1942 ng/mL (8.51 nmol/mL). The mean plasma elimination half-life was just over 1h.

(2) Tissue: Levels of resveratrol were below the LLOQ in all subjects on placebo and one of the six patients on SRT501. Mean resveratrol levels in the remaining five patients receiving SRT501 were 1098±1393 ng/g (4.81 nmol/g, range 52-2834 ng/g) and 420±341 ng/g (1.84 nmol/g, range 46-914 ng/g) in tumor and normal tissue, respectively.
|Bias arising from the randomization process=?
|Bias due to deviation from intended intervention (assignment to intervention)=?
|Bias due to deviation from intended intervention (adhering to intervention)=NA
|Bias due to missing outcome data=?
|Bias in measurement of the outcome=?
|Bias in selection of the reported result=?
|Other sources of bias=?
|Overall RoB judgment=?
|Order number=2
}}
{{Outcome
|Outcome type=Others
|Outcome name=PD (Pharmacodynamics)
|Outcome specification=Potential effects of SRT501 on processes relevant to cell survival and apoptosis were measured in plasma and tissue.
|Type of measurement=Blood Test, Histological examination
|Results during intervention=NA
|Results after intervention=Overall:
There was no difference between patients who received placebo or SRT501 in terms of plasma/serum levels of prostaglandin E2 (PGE-2) and vascular endothelial growth factor (VEGF). The analysed tissue samples show no significant differences between placebo and SRT501. Apoptosis, as reflected by immunohistochemistry for cleaved caspase 3 in tumor tissue, was significantly increased by 39% (to 1.44% total apoptotic cells, p=0.038) in patients on SRT501 compared to those taking placebo.
|Bias arising from the randomization process=?
|Bias due to deviation from intended intervention (assignment to intervention)=?
|Bias due to deviation from intended intervention (adhering to intervention)=NA
|Bias due to missing outcome data=?
|Bias in measurement of the outcome=?
|Bias in selection of the reported result=?
|Other sources of bias=?
|Overall RoB judgment=?
|Order number=3
}}
{{Outcome Overview}}
=Funding and Conflicts of Interest=

{{Funding and Conflicts of Interest
|Funding=Study was designed and sponsored by Sirtris
|Conflicts of Interest=According to authors no conflict of interest.
}}
=Further points for assessing the study=

{{Further points for assessing the study
|Samples sufficiently large=No
|power analysis performed=?
|reasons given for samples being too small according to power analysis=?
|Ethnicity mentioned=Yes
|Possibility of attention effects=NA
|Possibility of placebo effects=NA
|Other reasons=?
|Testing for normal distribution=?
|Correct application of statistical tests=?
|Correction for multiple testing=?
|Measurement of compliance=?
|Blinding reliable=?
|Check whether blinding was successful=?
|Consistent reporting in numbers=?
|sufficient washout period=?
|Tested for carry-over effects=?
|Were sequence effects tested=?
|Comprehensive and coherent reporting=?
|Were side effects systematically recorded=?
|Effect sizes reported=?
|Side effects taken into account in the interpretation of the results=?
|mono- or multicentric=?
|Ethics / CoI / Funding=?
}}
{{Additional Notes}}
=Additional Notes=

Howells et al. (2011): Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics

2024-08-08T10:22:44Z

CMensger:

{{Reference
|Reference=Publication: Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics
}}
{{Study Note}}
=Brief summary=
This study compared two groups of patients, all of whom had colorectal carcinoma (stage IV) with liver metastases and a life expectancy of more than 3 months. The patients received a resveratrol solution with micronized resveratrol (5.0 g) or a matching placebo once a day for approximately 14 days prior to surgical removal of the liver metastases. The purpose of the study was to assess the safety, pharmacokinetics and pharmacodynamics of the formulation (micronized resveratrol). The side effects were recorded in a daily diary according to fixed criteria. The two groups were comparable before treatment. Various side effects occurred, especially diarrhea, but the side effects were predominantly mild (grade 1). One patient discontinued the study due to diarrhea. One patient died after surgery due to peritonitis and liver failure, which, according to the study director, was not caused by resveratrol. The authors conclude that a 14-day intake of resveratrol (5.0 g) is well tolerated in colorectal cancer patients.

In dieser Studie wurden zwei Gruppen von Patienten miteinander verglichen, welche alle ein kolorektales Karzinom (Stadium IV) mit Lebermetastasen und eine Lebenserwartung von mehr als 3 Monaten hatten. Die Patienten haben ungefähr 14 Tage vor der operativen Entfernung der Lebermetastasen täglich eine Resveratrol-Lösung (5,0 g) oder ein passendes Placebo bekommen. Ziel der Studie war es, die Sicherheit, Pharmakokinetik und Pharmakodynamik der Formulierung (mikronisiertes Resveratrol) zu bewerten.Die Nebenwirkungen wurden mittels täglicher Tagebuchführung nach festen Kriterien erhoben. Die beiden Gruppen waren vor der Behandlung vergleichbar. Es traten verschiedene Nebenwirkungen v.a. Durchfall auf, allerdings waren die Nebenwirkungen überwiegend mild ausgeprägt (Grad 1). Ein Patient brach die Studie wegen Durchfall ab. Ein Patient starb nach der OP an einer Bauchfellentzündung und Leberversagen, was aber laut des Studienleiters nicht durch Resveratrol verursacht war. Die Autoren schließen, dass eine 14 tägige Einnahme von Resveratrol (5,0 g) bei Darmkrebspatienten gut verträglich ist.

=Study Design=

{{Study Design (RCT)
|Perspective=Prospective
|Centralized=Multicentric
|Blinding=Double
|Is randomized=Yes
|Cross-over=No
|Number of arms=2
}}
=Study characteristics=

{{RCT study general properties
|Inclusion criteria=Subjects (18 years or older) presenting with confirmed stage IV colorectal cancer and hepatic metastases, who had not received therapeutic intervention for their cancer within 6 weeks of study commencement and had a life expectancy of >3 months, were recruited into the study. All patients were due to undergo resection of liver metastases. Participants had to be physically capable of complying with the protocol and had a normal ECG and no history of HIV or hepatitis B/C.
|Exclusion criteria=Patient were asked to refrain from large quantities of resveratrol-containing foods and drinks such as peanuts, grapes, mulberries and alcohol within 48 h of scheduled PK collection days, and the day of surgical resection.
|N randomized=9
|Analysis=?
|Specifications on analyses=All nine subjects were analysed. This is a Phase I study about safety, pharmapharmacokinetics, pharmacodynamics and not an efficacy study.
PK: Statistical analyses for pharmacokinetic data included linear regression with 1/concentration weighting and descriptive statistics.
PD: Means were compared via one way, one sided ANOVA followed by Tukey’s post hoc test.
|Countries of data collection=United Kingdom
|LoE=2b Oxford 2009
|Outcome timeline=Patients ingested the formulation pre-operatively daily for a minimum of 10 and a maximum of 21 days, dependent upon surgical scheduling. Plasma samples for PK assessment were obtained on days 1 and 2, and on the day of surgical resection. Plasma for PD assessment was obtained pre-dose, immediately prior to, and during surgery. Diseased and normal adjacent hepatic tissue was resected 6-7 h after the last dose.
}}
=Characteristics of participants=

{{Characteristics of participants
|Setting=Palliative
|Types of cancer=Colorectal Cancer
|Stage cancer=Advanced Stage
|Cancer stage specification=Stage IV colorectal cancer and hepatic metastases
|Comorbidity=NI
|Current cancer therapy=Surgery
|Specifications on cancer therapies=Resection of liver metastases
|Previous cancer therapies=NI
|Gender=Mixed
|Gender specifications=SRT501 (resveratrol): Male (5), female (1)
Placebo: Male (1), female (2)
|Age groups=Adults (18+)
|Age groups specification=SRT501 (resveratrol): 68.5(10.8) years
Placebo: 64.3(6.35) years
}}
=Arms=

{{Arm
|Arm type=Intervention
|Number of participants (arm)=6
|Drop-out=0
|Drop-out reasons=NA
|Intervention=Resveratrol
|Dosage and regime=Oral (suspension) of microparticular resveratrol (SRT501): 1 x 5,0 g daily for approximately 14 days (minimum of 10 and a maximum of 21 days before surgery)
|One-time application=No
|Duration in days=14
|Side Effects / Interactions=AEs possibly or probably attributable to agent intake: They were primarily of a gastrointestinal nature, including nausea and diarrhoea, and mild in grade (grade 1 NCI CTC v3.0). Other AEs included chills, lethargy, rash, skin irritation and vascular flushing, which resolved without sequelae.
|Order number=1
}}
{{Arm
|Arm type=Placebo
|Number of participants (arm)=3
|Drop-out=0
|Drop-out reasons=NA
|Intervention=Placebo
|Dosage and regime=Oral (suspension) of placebo 1 x daily for approximately 14 days (minimum of 10 and a maximum of 21 days before surgery)
|One-time application=No
|Duration in days=14
|Side Effects / Interactions=One case of lethargy in the placebo group, which was ongoing at follow-up. One case with diarrhoea.
|Order number=2
}}
{{Arm Overview}}
=Outcomes=

{{Outcome
|Outcome type=Others
|Outcome name=PK (Pharmacokinetics)
|Outcome specification=Resveratrol pharmacokinetics in blood (1) and concentration in liver tissue (2):
(1) Patients’ plasma was analysed by HPLC-MS/MS for resveratrol.
(2) Resveratrol was quantified in tumor and normal adjacent hepatic tissues.
|Type of measurement=Blood Test, Histological examination
|Results during intervention=NA
|Results after intervention=Overall:
(1) Blood: Resveratrol concentrations were below the lower limits of quantitation (LLOQ) for all samples from subjects receiving placebo, and measurable in patients who received SRT501. Cmax levels were reached 2.8 h post-dose, and the mean maximum plasma concentration was 1942 ng/mL (8.51 nmol/mL). The mean plasma elimination half-life was just over 1h.

(2) Tissue: Levels of resveratrol were below the LLOQ in all subjects on placebo and one of the six patients on SRT501. Mean resveratrol levels in the remaining five patients receiving SRT501 were 1098±1393 ng/g (4.81 nmol/g, range 52-2834 ng/g) and 420±341 ng/g (1.84 nmol/g, range 46-914 ng/g) in tumor and normal tissue, respectively.
|Bias arising from the randomization process=?
|Bias due to deviation from intended intervention (assignment to intervention)=?
|Bias due to deviation from intended intervention (adhering to intervention)=NA
|Bias due to missing outcome data=?
|Bias in measurement of the outcome=?
|Bias in selection of the reported result=?
|Other sources of bias=?
|Overall RoB judgment=?
|Order number=1
}}
{{Outcome Overview}}
=Funding and Conflicts of Interest=

{{Funding and Conflicts of Interest
|Funding=Study was designed and sponsored by Sirtris
|Conflicts of Interest=According to authors no conflict of interest.
}}
=Further points for assessing the study=

{{Further points for assessing the study
|Samples sufficiently large=No
|power analysis performed=?
|reasons given for samples being too small according to power analysis=?
|Ethnicity mentioned=Yes
|Possibility of attention effects=NA
|Possibility of placebo effects=NA
|Other reasons=?
|Testing for normal distribution=?
|Correct application of statistical tests=?
|Correction for multiple testing=?
|Measurement of compliance=?
|Blinding reliable=?
|Check whether blinding was successful=?
|Consistent reporting in numbers=?
|sufficient washout period=?
|Tested for carry-over effects=?
|Were sequence effects tested=?
|Comprehensive and coherent reporting=?
|Were side effects systematically recorded=?
|Effect sizes reported=?
|Side effects taken into account in the interpretation of the results=?
|mono- or multicentric=?
|Ethics / CoI / Funding=?
}}
{{Additional Notes}}
=Additional Notes=

Howells et al. (2011): Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics

2024-08-08T10:21:58Z

CMensger:

{{Reference
|Reference=Publication: Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics
}}
{{Study Note}}
=Brief summary=
This study compared two groups of patients, all of whom had colorectal carcinoma (stage IV) with liver metastases and a life expectancy of more than 3 months. The patients received a resveratrol solution with micronized resveratrol (5.0 g) or a matching placebo once a day for approximately 14 days prior to surgical removal of the liver metastases. The purpose of the study was to assess the safety, pharmacokinetics and pharmacodynamics of the formulation (micronized resveratrol). The side effects were recorded in a daily diary according to fixed criteria. The two groups were comparable before treatment. Various side effects occurred, especially diarrhea, but the side effects were predominantly mild (grade 1). One patient discontinued the study due to diarrhea. One patient died after surgery due to peritonitis and liver failure, which, according to the study director, was not caused by resveratrol. The authors conclude that a 14-day intake of resveratrol (5.0 g) is well tolerated in colorectal cancer patients.

In dieser Studie wurden zwei Gruppen von Patienten miteinander verglichen, welche alle ein kolorektales Karzinom (Stadium IV) mit Lebermetastasen und eine Lebenserwartung von mehr als 3 Monaten hatten. Die Patienten haben ungefähr 14 Tage vor der operativen Entfernung der Lebermetastasen täglich eine Resveratrol-Lösung (5,0 g) oder ein passendes Placebo bekommen. Ziel der Studie war es, die Sicherheit, Pharmakokinetik und Pharmakodynamik der Formulierung (mikronisiertes Resveratrol) zu bewerten.Die Nebenwirkungen wurden mittels täglicher Tagebuchführung nach festen Kriterien erhoben. Die beiden Gruppen waren vor der Behandlung vergleichbar. Es traten verschiedene Nebenwirkungen v.a. Durchfall auf, allerdings waren die Nebenwirkungen überwiegend mild ausgeprägt (Grad 1). Ein Patient brach die Studie wegen Durchfall ab. Ein Patient starb nach der OP an einer Bauchfellentzündung und Leberversagen, was aber laut des Studienleiters nicht durch Resveratrol verursacht war. Die Autoren schließen, dass eine 14 tägige Einnahme von Resveratrol (5,0 g) bei Darmkrebspatienten gut verträglich ist.

=Study Design=

{{Study Design (RCT)
|Perspective=Prospective
|Centralized=Multicentric
|Blinding=Double
|Is randomized=Yes
|Cross-over=No
|Number of arms=2
}}
=Study characteristics=

{{RCT study general properties
|Inclusion criteria=Subjects (18 years or older) presenting with confirmed stage IV colorectal cancer and hepatic metastases, who had not received therapeutic intervention for their cancer within 6 weeks of study commencement and had a life expectancy of >3 months, were recruited into the study. All patients were due to undergo resection of liver metastases. Participants had to be physically capable of complying with the protocol and had a normal ECG and no history of HIV or hepatitis B/C.
|Exclusion criteria=Patient were asked to refrain from large quantities of resveratrol-containing foods and drinks such as peanuts, grapes, mulberries and alcohol within 48 h of scheduled PK collection days, and the day of surgical resection.
|N randomized=9
|Analysis=?
|Specifications on analyses=All nine subjects were analysed. This is a Phase I study about safety, pharmapharmacokinetics, pharmacodynamics and not an efficacy study.
PK: Statistical analyses for pharmacokinetic data included linear regression with 1/concentration weighting and descriptive statistics.
PD: Means were compared via one way, one sided ANOVA followed by Tukey’s post hoc test.
|Countries of data collection=United Kingdom
|LoE=2b Oxford 2009
|Outcome timeline=Patients ingested the formulation pre-operatively daily for a minimum of 10 and a maximum of 21 days, dependent upon surgical scheduling. Plasma samples for PK assessment were obtained on days 1 and 2, and on the day of surgical resection. Plasma for PD assessment was obtained pre-dose, immediately prior to, and during surgery. Diseased and normal adjacent hepatic tissue was resected 6-7 h after the last dose.
}}
=Characteristics of participants=

{{Characteristics of participants
|Setting=Palliative
|Types of cancer=Colorectal Cancer
|Stage cancer=Advanced Stage
|Cancer stage specification=Stage IV colorectal cancer and hepatic metastases
|Comorbidity=NI
|Current cancer therapy=Surgery
|Specifications on cancer therapies=Resection of liver metastases
|Previous cancer therapies=NI
|Gender=Mixed
|Gender specifications=SRT501 (resveratrol): Male (5), female (1)
Placebo: Male (1), female (2)
|Age groups=Adults (18+)
|Age groups specification=SRT501 (resveratrol): 68.5(10.8) years
Placebo: 64.3(6.35) years
}}
=Arms=

{{Arm
|Arm type=Intervention
|Number of participants (arm)=6
|Drop-out=0
|Drop-out reasons=NA
|Intervention=Resveratrol
|Dosage and regime=Oral (suspension) of microparticular resveratrol (SRT501): 1 x 5,0 g daily for approximately 14 days (minimum of 10 and a maximum of 21 days before surgery)
|One-time application=No
|Duration in days=14
|Side Effects / Interactions=AEs possibly or probably attributable to agent intake: They were primarily of a gastrointestinal nature, including nausea and diarrhoea, and mild in grade (grade 1 NCI CTC v3.0). Other AEs included chills, lethargy, rash, skin irritation and vascular flushing, which resolved without sequelae.
|Order number=1
}}
{{Arm
|Arm type=Placebo
|Number of participants (arm)=3
|Drop-out=0
|Drop-out reasons=NA
|Intervention=Placebo
|Dosage and regime=Oral (suspension) of placebo 1 x daily for approximately 14 days (minimum of 10 and a maximum of 21 days before surgery)
|One-time application=No
|Duration in days=14
|Side Effects / Interactions=One case of lethargy in the placebo group, which was ongoing at follow-up. One case with diarrhoea.
|Order number=2
}}
{{Arm Overview}}
=Outcomes=

{{Outcome
|Outcome type=Others
|Outcome name=PK (Pharmacokinetics)
|Outcome specification=Resveratrol pharmacokinetics in blood (1) and concentration in liver tissue (2):
(1) Patients’ plasma was analysed by HPLC-MS/MS for resveratrol.
(2) Resveratrol was quantified in tumor and normal adjacent hepatic tissues.
|Type of measurement=Blood Test, Histological examination
|Results during intervention=?
|Results after intervention=Overall:
(1) Blood: Resveratrol concentrations were below the lower limits of quantitation (LLOQ) for all samples from subjects receiving placebo, and measurable in patients who received SRT501. Cmax levels were reached 2.8 h post-dose, and the mean maximum plasma concentration was 1942 ng/mL (8.51 nmol/mL). The mean plasma elimination half-life was just over 1h.

(2) Tissue: Levels of resveratrol were below the LLOQ in all subjects on placebo and one of the six patients on SRT501. Mean resveratrol levels in the remaining five patients receiving SRT501 were 1098±1393 ng/g (4.81 nmol/g, range 52-2834 ng/g) and 420±341 ng/g (1.84 nmol/g, range 46-914 ng/g) in tumor and normal tissue, respectively.
|Bias arising from the randomization process=?
|Bias due to deviation from intended intervention (assignment to intervention)=?
|Bias due to deviation from intended intervention (adhering to intervention)=NA
|Bias due to missing outcome data=?
|Bias in measurement of the outcome=?
|Bias in selection of the reported result=?
|Other sources of bias=?
|Overall RoB judgment=?
|Order number=1
}}
{{Outcome Overview}}
=Funding and Conflicts of Interest=

{{Funding and Conflicts of Interest
|Funding=Study was designed and sponsored by Sirtris
|Conflicts of Interest=According to authors no conflict of interest.
}}
=Further points for assessing the study=

{{Further points for assessing the study
|Samples sufficiently large=No
|power analysis performed=?
|reasons given for samples being too small according to power analysis=?
|Ethnicity mentioned=Yes
|Possibility of attention effects=NA
|Possibility of placebo effects=NA
|Other reasons=?
|Testing for normal distribution=?
|Correct application of statistical tests=?
|Correction for multiple testing=?
|Measurement of compliance=?
|Blinding reliable=?
|Check whether blinding was successful=?
|Consistent reporting in numbers=?
|sufficient washout period=?
|Tested for carry-over effects=?
|Were sequence effects tested=?
|Comprehensive and coherent reporting=?
|Were side effects systematically recorded=?
|Effect sizes reported=?
|Side effects taken into account in the interpretation of the results=?
|mono- or multicentric=?
|Ethics / CoI / Funding=?
}}
{{Additional Notes}}
=Additional Notes=

Howells et al. (2011): Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics

2024-08-08T10:20:58Z

CMensger:

{{Reference
|Reference=Publication: Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics
}}
{{Study Note}}
=Brief summary=
This study compared two groups of patients, all of whom had colorectal carcinoma (stage IV) with liver metastases and a life expectancy of more than 3 months. The patients received a resveratrol solution with micronized resveratrol (5.0 g) or a matching placebo once a day for approximately 14 days prior to surgical removal of the liver metastases. The purpose of the study was to assess the safety, pharmacokinetics and pharmacodynamics of the formulation (micronized resveratrol). The side effects were recorded in a daily diary according to fixed criteria. The two groups were comparable before treatment. Various side effects occurred, especially diarrhea, but the side effects were predominantly mild (grade 1). One patient discontinued the study due to diarrhea. One patient died after surgery due to peritonitis and liver failure, which, according to the study director, was not caused by resveratrol. The authors conclude that a 14-day intake of resveratrol (5.0 g) is well tolerated in colorectal cancer patients.

In dieser Studie wurden zwei Gruppen von Patienten miteinander verglichen, welche alle ein kolorektales Karzinom (Stadium IV) mit Lebermetastasen und eine Lebenserwartung von mehr als 3 Monaten hatten. Die Patienten haben ungefähr 14 Tage vor der operativen Entfernung der Lebermetastasen täglich eine Resveratrol-Lösung (5,0 g) oder ein passendes Placebo bekommen. Ziel der Studie war es, die Sicherheit, Pharmakokinetik und Pharmakodynamik der Formulierung (mikronisiertes Resveratrol) zu bewerten.Die Nebenwirkungen wurden mittels täglicher Tagebuchführung nach festen Kriterien erhoben. Die beiden Gruppen waren vor der Behandlung vergleichbar. Es traten verschiedene Nebenwirkungen v.a. Durchfall auf, allerdings waren die Nebenwirkungen überwiegend mild ausgeprägt (Grad 1). Ein Patient brach die Studie wegen Durchfall ab. Ein Patient starb nach der OP an einer Bauchfellentzündung und Leberversagen, was aber laut des Studienleiters nicht durch Resveratrol verursacht war. Die Autoren schließen, dass eine 14 tägige Einnahme von Resveratrol (5,0 g) bei Darmkrebspatienten gut verträglich ist.

=Study Design=

{{Study Design (RCT)
|Perspective=Prospective
|Centralized=Multicentric
|Blinding=Double
|Is randomized=Yes
|Cross-over=No
|Number of arms=2
}}
=Study characteristics=

{{RCT study general properties
|Inclusion criteria=Subjects (18 years or older) presenting with confirmed stage IV colorectal cancer and hepatic metastases, who had not received therapeutic intervention for their cancer within 6 weeks of study commencement and had a life expectancy of >3 months, were recruited into the study. All patients were due to undergo resection of liver metastases. Participants had to be physically capable of complying with the protocol and had a normal ECG and no history of HIV or hepatitis B/C.
|Exclusion criteria=Patient were asked to refrain from large quantities of resveratrol-containing foods and drinks such as peanuts, grapes, mulberries and alcohol within 48 h of scheduled PK collection days, and the day of surgical resection.
|N randomized=9
|Analysis=?
|Specifications on analyses=All nine subjects were analysed. This is a Phase I study about safety, pharmapharmacokinetics, pharmacodynamics and not an efficacy study.
PK: Statistical analyses for pharmacokinetic data included linear regression with 1/concentration weighting and descriptive statistics.
PD: Means were compared via one way, one sided ANOVA followed by Tukey’s post hoc test.
|Countries of data collection=United Kingdom
|LoE=2b Oxford 2009
|Outcome timeline=Patients ingested the formulation pre-operatively daily for a minimum of 10 and a maximum of 21 days, dependent upon surgical scheduling. Plasma samples for PK assessment were obtained on days 1 and 2, and on the day of surgical resection. Plasma for PD assessment was obtained pre-dose, immediately prior to, and during surgery. Diseased and normal adjacent hepatic tissue was resected 6-7 h after the last dose.
}}
=Characteristics of participants=

{{Characteristics of participants
|Setting=Palliative
|Types of cancer=Colorectal Cancer
|Stage cancer=Advanced Stage
|Cancer stage specification=Stage IV colorectal cancer and hepatic metastases
|Comorbidity=NI
|Current cancer therapy=Surgery
|Specifications on cancer therapies=Resection of liver metastases
|Previous cancer therapies=NI
|Gender=Mixed
|Gender specifications=SRT501 (resveratrol): Male (5), female (1)
Placebo: Male (1), female (2)
|Age groups=Adults (18+)
|Age groups specification=SRT501 (resveratrol): 68.5(10.8) years
Placebo: 64.3(6.35) years
}}
=Arms=

{{Arm
|Arm type=Intervention
|Number of participants (arm)=6
|Drop-out=0
|Drop-out reasons=NA
|Intervention=Resveratrol
|Dosage and regime=Oral (suspension) of microparticular resveratrol (SRT501): 1 x 5,0 g daily for approximately 14 days (minimum of 10 and a maximum of 21 days before surgery)
|One-time application=No
|Duration in days=14
|Side Effects / Interactions=AEs possibly or probably attributable to agent intake: They were primarily of a gastrointestinal nature, including nausea and diarrhoea, and mild in grade (grade 1 NCI CTC v3.0). Other AEs included chills, lethargy, rash, skin irritation and vascular flushing, which resolved without sequelae.
|Order number=1
}}
{{Arm
|Arm type=Placebo
|Number of participants (arm)=3
|Drop-out=0
|Drop-out reasons=NA
|Intervention=Placebo
|Dosage and regime=Oral (suspension) of placebo 1 x daily for approximately 14 days (minimum of 10 and a maximum of 21 days before surgery)
|One-time application=No
|Duration in days=14
|Side Effects / Interactions=One case of lethargy in the placebo group, which was ongoing at follow-up. One case with diarrhoea.
|Order number=2
}}
{{Arm Overview}}
=Outcomes=

{{Outcome
|Outcome type=Others
|Outcome name=PK (Pharmacokinetics)
|Outcome specification=Resveratrol pharmacokinetics in blood (1) and concentration in liver tissue (2):
(1) Patients’ plasma was analysed by HPLC-MS/MS for resveratrol.
(2) Resveratrol was quantified in tumor and normal adjacent hepatic tissues.
|Type of measurement=Blood Test, Histological examination
|Results during intervention=?
|Results after intervention=Overall:
(1) Blood: Resveratrol concentrations were below the lower limits of quantitation (LLOQ) for all samples from subjects receiving placebo, and measurable in patients who received SRT501. Cmax levels were reached 2.8 h post-dose, and the mean maximum plasma concentration was 1942 ng/mL (8.51 nmol/mL). The mean plasma elimination half-life was just over 1h.
(2) Tissue: Levels of resveratrol were below the LLOQ in all subjects on placebo and one of the six patients on SRT501. Mean resveratrol levels in the remaining five patients receiving SRT501 were 1098±1393 ng/g (4.81 nmol/g, range 52-2834 ng/g) and 420±341 ng/g (1.84 nmol/g, range 46-914 ng/g) in tumor and normal tissue, respectively.
|Bias arising from the randomization process=?
|Bias due to deviation from intended intervention (assignment to intervention)=?
|Bias due to deviation from intended intervention (adhering to intervention)=NA
|Bias due to missing outcome data=?
|Bias in measurement of the outcome=?
|Bias in selection of the reported result=?
|Other sources of bias=?
|Overall RoB judgment=?
|Order number=1
}}
{{Outcome Overview}}
=Funding and Conflicts of Interest=

{{Funding and Conflicts of Interest
|Funding=Study was designed and sponsored by Sirtris
|Conflicts of Interest=According to authors no conflict of interest.
}}
=Further points for assessing the study=

{{Further points for assessing the study
|Samples sufficiently large=No
|power analysis performed=?
|reasons given for samples being too small according to power analysis=?
|Ethnicity mentioned=Yes
|Possibility of attention effects=NA
|Possibility of placebo effects=NA
|Other reasons=?
|Testing for normal distribution=?
|Correct application of statistical tests=?
|Correction for multiple testing=?
|Measurement of compliance=?
|Blinding reliable=?
|Check whether blinding was successful=?
|Consistent reporting in numbers=?
|sufficient washout period=?
|Tested for carry-over effects=?
|Were sequence effects tested=?
|Comprehensive and coherent reporting=?
|Were side effects systematically recorded=?
|Effect sizes reported=?
|Side effects taken into account in the interpretation of the results=?
|mono- or multicentric=?
|Ethics / CoI / Funding=?
}}
{{Additional Notes}}
=Additional Notes=

Howells et al. (2011): Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics

2024-08-08T10:18:13Z

CMensger:

{{Reference
|Reference=Publication: Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics
}}
{{Study Note}}
=Brief summary=
This study compared two groups of patients, all of whom had colorectal carcinoma (stage IV) with liver metastases and a life expectancy of more than 3 months. The patients received a resveratrol solution with micronized resveratrol (5.0 g) or a matching placebo once a day for approximately 14 days prior to surgical removal of the liver metastases. The purpose of the study was to assess the safety, pharmacokinetics and pharmacodynamics of the formulation (micronized resveratrol). The side effects were recorded in a daily diary according to fixed criteria. The two groups were comparable before treatment. Various side effects occurred, especially diarrhea, but the side effects were predominantly mild (grade 1). One patient discontinued the study due to diarrhea. One patient died after surgery due to peritonitis and liver failure, which, according to the study director, was not caused by resveratrol. The authors conclude that a 14-day intake of resveratrol (5.0 g) is well tolerated in colorectal cancer patients.

In dieser Studie wurden zwei Gruppen von Patienten miteinander verglichen, welche alle ein kolorektales Karzinom (Stadium IV) mit Lebermetastasen und eine Lebenserwartung von mehr als 3 Monaten hatten. Die Patienten haben ungefähr 14 Tage vor der operativen Entfernung der Lebermetastasen täglich eine Resveratrol-Lösung (5,0 g) oder ein passendes Placebo bekommen. Ziel der Studie war es, die Sicherheit, Pharmakokinetik und Pharmakodynamik der Formulierung (mikronisiertes Resveratrol) zu bewerten.Die Nebenwirkungen wurden mittels täglicher Tagebuchführung nach festen Kriterien erhoben. Die beiden Gruppen waren vor der Behandlung vergleichbar. Es traten verschiedene Nebenwirkungen v.a. Durchfall auf, allerdings waren die Nebenwirkungen überwiegend mild ausgeprägt (Grad 1). Ein Patient brach die Studie wegen Durchfall ab. Ein Patient starb nach der OP an einer Bauchfellentzündung und Leberversagen, was aber laut des Studienleiters nicht durch Resveratrol verursacht war. Die Autoren schließen, dass eine 14 tägige Einnahme von Resveratrol (5,0 g) bei Darmkrebspatienten gut verträglich ist.

=Study Design=

{{Study Design (RCT)
|Perspective=Prospective
|Centralized=Multicentric
|Blinding=Double
|Is randomized=Yes
|Cross-over=No
|Number of arms=2
}}
=Study characteristics=

{{RCT study general properties
|Inclusion criteria=Subjects (18 years or older) presenting with confirmed stage IV colorectal cancer and hepatic metastases, who had not received therapeutic intervention for their cancer within 6 weeks of study commencement and had a life expectancy of >3 months, were recruited into the study. All patients were due to undergo resection of liver metastases. Participants had to be physically capable of complying with the protocol and had a normal ECG and no history of HIV or hepatitis B/C.
|Exclusion criteria=Patient were asked to refrain from large quantities of resveratrol-containing foods and drinks such as peanuts, grapes, mulberries and alcohol within 48 h of scheduled PK collection days, and the day of surgical resection.
|N randomized=9
|Analysis=?
|Specifications on analyses=All nine subjects were analysed. This is a Phase I study about safety, pharmapharmacokinetics, pharmacodynamics and not an efficacy study.
PK: Statistical analyses for pharmacokinetic data included linear regression with 1/concentration weighting and descriptive statistics.
PD: Means were compared via one way, one sided ANOVA followed by Tukey’s post hoc test.
|Countries of data collection=United Kingdom
|LoE=2b Oxford 2009
|Outcome timeline=Patients ingested the formulation pre-operatively daily for a minimum of 10 and a maximum of 21 days, dependent upon surgical scheduling. Plasma samples for PK assessment were obtained on days 1 and 2, and on the day of surgical resection. Plasma for PD assessment was obtained pre-dose, immediately prior to, and during surgery. Diseased and normal adjacent hepatic tissue was resected 6-7 h after the last dose.
}}
=Characteristics of participants=

{{Characteristics of participants
|Setting=Palliative
|Types of cancer=Colorectal Cancer
|Stage cancer=Advanced Stage
|Cancer stage specification=Stage IV colorectal cancer and hepatic metastases
|Comorbidity=NI
|Current cancer therapy=Surgery
|Specifications on cancer therapies=Resection of liver metastases
|Previous cancer therapies=NI
|Gender=Mixed
|Gender specifications=SRT501 (resveratrol): Male (5), female (1)
Placebo: Male (1), female (2)
|Age groups=Adults (18+)
|Age groups specification=SRT501 (resveratrol): 68.5(10.8) years
Placebo: 64.3(6.35) years
}}
=Arms=

{{Arm
|Arm type=Intervention
|Number of participants (arm)=6
|Drop-out=0
|Drop-out reasons=NA
|Intervention=Resveratrol
|Dosage and regime=Oral (suspension) of microparticular resveratrol (SRT501): 1 x 5,0 g daily for approximately 14 days (minimum of 10 and a maximum of 21 days before surgery)
|One-time application=No
|Duration in days=14
|Side Effects / Interactions=AEs possibly or probably attributable to agent intake: They were primarily of a gastrointestinal nature, including nausea and diarrhoea, and mild in grade (grade 1 NCI CTC v3.0). Other AEs included chills, lethargy, rash, skin irritation and vascular flushing, which resolved without sequelae.
|Order number=1
}}
{{Arm
|Arm type=Placebo
|Number of participants (arm)=3
|Drop-out=0
|Drop-out reasons=NA
|Intervention=Placebo
|Dosage and regime=Oral (suspension) of placebo 1 x daily for approximately 14 days (minimum of 10 and a maximum of 21 days before surgery)
|One-time application=No
|Duration in days=14
|Side Effects / Interactions=One case of lethargy in the placebo group, which was ongoing at follow-up. One case with diarrhoea.
|Order number=2
}}
{{Arm Overview}}
=Outcomes=

{{Outcome
|Outcome type=Others
|Outcome name=PK (Pharmacokinetics)
|Outcome specification=Resveratrol pharmacokinetics in blood (1) and concentration in liver tissue (2):
(1) Patients’ plasma was analysed by HPLC-MS/MS for resveratrol.
(2) Resveratrol was quantified in tumor and normal adjacent hepatic tissues.
|Type of measurement=Blood Test, Histological examination
|Results during intervention=(1) Resveratrol concentrations were below the lower limits of quantitation (LLOQ) for all samples from subjects receiving placebo, and measurable in patients who received SRT501. Cmax levels were reached 2.8 h post-dose, and the mean maximum plasma concentration was 1942 ng/mL (8.51 nmol/mL). The mean plasma elimination half-life was just over 1h.
(2) Levels of resveratrol were below the LLOQ in all subjects on placebo and one of the six patients on SRT501. Mean resveratrol levels in the remaining five patients receiving SRT501 were 1098±1393 ng/g (4.81 nmol/g, range 52-2834 ng/g) and 420±341 ng/g (1.84 nmol/g, range 46-914 ng/g) in tumor and normal tissue, respectively.
|Results after intervention=Overall:
(1) Resveratrol concentrations were below the lower limits of quantitation (LLOQ) for all samples from subjects receiving placebo, and measurable in patients who received SRT501. Cmax levels were reached 2.8 h post-dose, and the mean maximum plasma concentration was 1942 ng/mL (8.51 nmol/mL). The mean plasma elimination half-life was just over 1h.
(2) Levels of resveratrol were below the LLOQ in all subjects on placebo and one of the six patients on SRT501. Mean resveratrol levels in the remaining five patients receiving SRT501 were 1098±1393 ng/g (4.81 nmol/g, range 52-2834 ng/g) and 420±341 ng/g (1.84 nmol/g, range 46-914 ng/g) in tumor and normal tissue, respectively.
|Bias arising from the randomization process=?
|Bias due to deviation from intended intervention (assignment to intervention)=?
|Bias due to deviation from intended intervention (adhering to intervention)=NA
|Bias due to missing outcome data=?
|Bias in measurement of the outcome=?
|Bias in selection of the reported result=?
|Other sources of bias=?
|Overall RoB judgment=?
|Order number=1
}}
{{Outcome Overview}}
=Funding and Conflicts of Interest=

{{Funding and Conflicts of Interest
|Funding=Study was designed and sponsored by Sirtris
|Conflicts of Interest=According to authors no conflict of interest.
}}
=Further points for assessing the study=

{{Further points for assessing the study
|Samples sufficiently large=No
|power analysis performed=?
|reasons given for samples being too small according to power analysis=?
|Ethnicity mentioned=Yes
|Possibility of attention effects=NA
|Possibility of placebo effects=NA
|Other reasons=?
|Testing for normal distribution=?
|Correct application of statistical tests=?
|Correction for multiple testing=?
|Measurement of compliance=?
|Blinding reliable=?
|Check whether blinding was successful=?
|Consistent reporting in numbers=?
|sufficient washout period=?
|Tested for carry-over effects=?
|Were sequence effects tested=?
|Comprehensive and coherent reporting=?
|Were side effects systematically recorded=?
|Effect sizes reported=?
|Side effects taken into account in the interpretation of the results=?
|mono- or multicentric=?
|Ethics / CoI / Funding=?
}}
{{Additional Notes}}
=Additional Notes=

Howells et al. (2011): Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics

2024-08-08T10:15:39Z

CMensger:

{{Reference
|Reference=Publication: Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics
}}
{{Study Note}}
=Brief summary=
This study compared two groups of patients, all of whom had colorectal carcinoma (stage IV) with liver metastases and a life expectancy of more than 3 months. The patients received a resveratrol solution with micronized resveratrol (5.0 g) or a matching placebo once a day for approximately 14 days prior to surgical removal of the liver metastases. The purpose of the study was to assess the safety, pharmacokinetics and pharmacodynamics of the formulation (micronized resveratrol). The side effects were recorded in a daily diary according to fixed criteria. The two groups were comparable before treatment. Various side effects occurred, especially diarrhea, but the side effects were predominantly mild (grade 1). One patient discontinued the study due to diarrhea. One patient died after surgery due to peritonitis and liver failure, which, according to the study director, was not caused by resveratrol. The authors conclude that a 14-day intake of resveratrol (5.0 g) is well tolerated in colorectal cancer patients.

In dieser Studie wurden zwei Gruppen von Patienten miteinander verglichen, welche alle ein kolorektales Karzinom (Stadium IV) mit Lebermetastasen und eine Lebenserwartung von mehr als 3 Monaten hatten. Die Patienten haben ungefähr 14 Tage vor der operativen Entfernung der Lebermetastasen täglich eine Resveratrol-Lösung (5,0 g) oder ein passendes Placebo bekommen. Ziel der Studie war es, die Sicherheit, Pharmakokinetik und Pharmakodynamik der Formulierung (mikronisiertes Resveratrol) zu bewerten.Die Nebenwirkungen wurden mittels täglicher Tagebuchführung nach festen Kriterien erhoben. Die beiden Gruppen waren vor der Behandlung vergleichbar. Es traten verschiedene Nebenwirkungen v.a. Durchfall auf, allerdings waren die Nebenwirkungen überwiegend mild ausgeprägt (Grad 1). Ein Patient brach die Studie wegen Durchfall ab. Ein Patient starb nach der OP an einer Bauchfellentzündung und Leberversagen, was aber laut des Studienleiters nicht durch Resveratrol verursacht war. Die Autoren schließen, dass eine 14 tägige Einnahme von Resveratrol (5,0 g) bei Darmkrebspatienten gut verträglich ist.

=Study Design=

{{Study Design (RCT)
|Perspective=Prospective
|Centralized=Multicentric
|Blinding=Double
|Is randomized=Yes
|Cross-over=No
|Number of arms=2
}}
=Study characteristics=

{{RCT study general properties
|Inclusion criteria=Subjects (18 years or older) presenting with confirmed stage IV colorectal cancer and hepatic metastases, who had not received therapeutic intervention for their cancer within 6 weeks of study commencement and had a life expectancy of >3 months, were recruited into the study. All patients were due to undergo resection of liver metastases. Participants had to be physically capable of complying with the protocol and had a normal ECG and no history of HIV or hepatitis B/C.
|Exclusion criteria=Patient were asked to refrain from large quantities of resveratrol-containing foods and drinks such as peanuts, grapes, mulberries and alcohol within 48 h of scheduled PK collection days, and the day of surgical resection.
|N randomized=9
|Analysis=?
|Specifications on analyses=All nine subjects were analysed. This is a Phase I study about safety, pharmapharmacokinetics, pharmacodynamics and not an efficacy study.
PK: Statistical analyses for pharmacokinetic data included linear regression with 1/concentration weighting and descriptive statistics.
PD: Means were compared via one way, one sided ANOVA followed by Tukey’s post hoc test.
|Countries of data collection=United Kingdom
|LoE=2b Oxford 2009
|Outcome timeline=Patients ingested the formulation pre-operatively daily for a minimum of 10 and a maximum of 21 days, dependent upon surgical scheduling. Plasma samples for PK assessment were obtained on days 1 and 2, and on the day of surgical resection. Plasma for PD assessment was obtained pre-dose, immediately prior to, and during surgery. Diseased and normal adjacent hepatic tissue was resected 6-7 h after the last dose.
}}
=Characteristics of participants=

{{Characteristics of participants
|Setting=Palliative
|Types of cancer=Colorectal Cancer
|Stage cancer=Advanced Stage
|Cancer stage specification=Stage IV colorectal cancer and hepatic metastases
|Comorbidity=NI
|Current cancer therapy=Surgery
|Specifications on cancer therapies=Resection of liver metastases
|Previous cancer therapies=NI
|Gender=Mixed
|Gender specifications=SRT501 (resveratrol): Male (5), female (1)
Placebo: Male (1), female (2)
|Age groups=Adults (18+)
|Age groups specification=SRT501 (resveratrol): 68.5(10.8) years
Placebo: 64.3(6.35) years
}}
=Arms=

{{Arm
|Arm type=Intervention
|Number of participants (arm)=6
|Drop-out=0
|Drop-out reasons=NA
|Intervention=Resveratrol
|Dosage and regime=Oral (suspension) of microparticular resveratrol (SRT501): 1 x 5,0 g daily for approximately 14 days (minimum of 10 and a maximum of 21 days before surgery)
|One-time application=No
|Duration in days=14
|Side Effects / Interactions=AEs possibly or probably attributable to agent intake: They were primarily of a gastrointestinal nature, including nausea and diarrhoea, and mild in grade (grade 1 NCI CTC v3.0). Other AEs included chills, lethargy, rash, skin irritation and vascular flushing, which resolved without sequelae.
|Order number=1
}}
{{Arm
|Arm type=Placebo
|Number of participants (arm)=3
|Drop-out=0
|Drop-out reasons=NA
|Intervention=Placebo
|Dosage and regime=Oral (suspension) of placebo 1 x daily for approximately 14 days (minimum of 10 and a maximum of 21 days before surgery)
|One-time application=No
|Duration in days=14
|Side Effects / Interactions=One case of lethargy in the placebo group, which was ongoing at follow-up. One case with diarrhoea.
|Order number=2
}}
{{Arm Overview}}
=Outcomes=

{{Outcome
|Outcome type=Others
|Outcome name=PK (Pharmacokinetics)
|Outcome specification=Resveratrol pharmacokinetics (1) and concentration in liver tissue (2):
(1) Patients’ plasma was analysed by HPLC-MS/MS for resveratrol.
(2) Resveratrol was quantified in tumor and normal adjacent hepatic tissues.
|Type of measurement=Blood Test, Histological examination
|Results during intervention=(1) Resveratrol concentrations were below the lower limits of quantitation (LLOQ) for all samples from subjects receiving placebo, and measurable in patients who received SRT501. Cmax levels were reached 2.8 h post-dose, and the mean maximum plasma concentration was 1942 ng/mL (8.51 nmol/mL). The mean plasma elimination half-life was just over 1h.
(2) Levels of resveratrol were below the LLOQ in all subjects on placebo and one of the six patients on SRT501. Mean resveratrol levels in the remaining five patients receiving SRT501 were 1098±1393 ng/g (4.81 nmol/g, range 52-2834 ng/g) and 420±341 ng/g (1.84 nmol/g, range 46-914 ng/g) in tumor and normal tissue, respectively.
|Results after intervention=?
|Bias arising from the randomization process=?
|Bias due to deviation from intended intervention (assignment to intervention)=?
|Bias due to deviation from intended intervention (adhering to intervention)=NA
|Bias due to missing outcome data=?
|Bias in measurement of the outcome=?
|Bias in selection of the reported result=?
|Other sources of bias=?
|Overall RoB judgment=?
|Order number=1
}}
{{Outcome Overview}}
=Funding and Conflicts of Interest=

{{Funding and Conflicts of Interest
|Funding=Study was designed and sponsored by Sirtris
|Conflicts of Interest=According to authors no conflict of interest.
}}
=Further points for assessing the study=

{{Further points for assessing the study
|Samples sufficiently large=No
|power analysis performed=?
|reasons given for samples being too small according to power analysis=?
|Ethnicity mentioned=Yes
|Possibility of attention effects=NA
|Possibility of placebo effects=NA
|Other reasons=?
|Testing for normal distribution=?
|Correct application of statistical tests=?
|Correction for multiple testing=?
|Measurement of compliance=?
|Blinding reliable=?
|Check whether blinding was successful=?
|Consistent reporting in numbers=?
|sufficient washout period=?
|Tested for carry-over effects=?
|Were sequence effects tested=?
|Comprehensive and coherent reporting=?
|Were side effects systematically recorded=?
|Effect sizes reported=?
|Side effects taken into account in the interpretation of the results=?
|mono- or multicentric=?
|Ethics / CoI / Funding=?
}}
{{Additional Notes}}
=Additional Notes=

Howells et al. (2011): Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics

2024-08-08T10:05:58Z

CMensger:

{{Reference
|Reference=Publication: Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics
}}
{{Study Note}}
=Brief summary=
This study compared two groups of patients, all of whom had colorectal carcinoma (stage IV) with liver metastases and a life expectancy of more than 3 months. The patients received a resveratrol solution with micronized resveratrol (5.0 g) or a matching placebo once a day for approximately 14 days prior to surgical removal of the liver metastases. The purpose of the study was to assess the safety, pharmacokinetics and pharmacodynamics of the formulation (micronized resveratrol). The side effects were recorded in a daily diary according to fixed criteria. The two groups were comparable before treatment. Various side effects occurred, especially diarrhea, but the side effects were predominantly mild (grade 1). One patient discontinued the study due to diarrhea. One patient died after surgery due to peritonitis and liver failure, which, according to the study director, was not caused by resveratrol. The authors conclude that a 14-day intake of resveratrol (5.0 g) is well tolerated in colorectal cancer patients.

In dieser Studie wurden zwei Gruppen von Patienten miteinander verglichen, welche alle ein kolorektales Karzinom (Stadium IV) mit Lebermetastasen und eine Lebenserwartung von mehr als 3 Monaten hatten. Die Patienten haben ungefähr 14 Tage vor der operativen Entfernung der Lebermetastasen täglich eine Resveratrol-Lösung (5,0 g) oder ein passendes Placebo bekommen. Ziel der Studie war es, die Sicherheit, Pharmakokinetik und Pharmakodynamik der Formulierung (mikronisiertes Resveratrol) zu bewerten.Die Nebenwirkungen wurden mittels täglicher Tagebuchführung nach festen Kriterien erhoben. Die beiden Gruppen waren vor der Behandlung vergleichbar. Es traten verschiedene Nebenwirkungen v.a. Durchfall auf, allerdings waren die Nebenwirkungen überwiegend mild ausgeprägt (Grad 1). Ein Patient brach die Studie wegen Durchfall ab. Ein Patient starb nach der OP an einer Bauchfellentzündung und Leberversagen, was aber laut des Studienleiters nicht durch Resveratrol verursacht war. Die Autoren schließen, dass eine 14 tägige Einnahme von Resveratrol (5,0 g) bei Darmkrebspatienten gut verträglich ist.

=Study Design=

{{Study Design (RCT)
|Perspective=Prospective
|Centralized=Multicentric
|Blinding=Double
|Is randomized=Yes
|Cross-over=No
|Number of arms=2
}}
=Study characteristics=

{{RCT study general properties
|Inclusion criteria=Subjects (18 years or older) presenting with confirmed stage IV colorectal cancer and hepatic metastases, who had not received therapeutic intervention for their cancer within 6 weeks of study commencement and had a life expectancy of >3 months, were recruited into the study. All patients were due to undergo resection of liver metastases. Participants had to be physically capable of complying with the protocol and had a normal ECG and no history of HIV or hepatitis B/C.
|Exclusion criteria=Patient were asked to refrain from large quantities of resveratrol-containing foods and drinks such as peanuts, grapes, mulberries and alcohol within 48 h of scheduled PK collection days, and the day of surgical resection.
|N randomized=9
|Analysis=?
|Specifications on analyses=All nine subjects were analysed. This is a Phase I study about safety, pharmapharmacokinetics, pharmacodynamics and not an efficacy study.
PK: Statistical analyses for pharmacokinetic data included linear regression with 1/concentration weighting and descriptive statistics.
PD: Means were compared via one way, one sided ANOVA followed by Tukey’s post hoc test.
|Countries of data collection=United Kingdom
|LoE=2b Oxford 2009
|Outcome timeline=Patients ingested the formulation pre-operatively daily for a minimum of 10 and a maximum of 21 days, dependent upon surgical scheduling. Plasma samples for PK assessment were obtained on days 1 and 2, and on the day of surgical resection. Plasma for PD assessment was obtained pre-dose, immediately prior to, and during surgery. Diseased and normal adjacent hepatic tissue was resected 6-7 h after the last dose.
}}
=Characteristics of participants=

{{Characteristics of participants
|Setting=Palliative
|Types of cancer=Colorectal Cancer
|Stage cancer=Advanced Stage
|Cancer stage specification=Stage IV colorectal cancer and hepatic metastases
|Comorbidity=NI
|Current cancer therapy=Surgery
|Specifications on cancer therapies=Resection of liver metastases
|Previous cancer therapies=NI
|Gender=Mixed
|Gender specifications=SRT501 (resveratrol): Male (5), female (1)
Placebo: Male (1), female (2)
|Age groups=Adults (18+)
|Age groups specification=SRT501 (resveratrol): 68.5(10.8) years
Placebo: 64.3(6.35) years
}}
=Arms=

{{Arm
|Arm type=Intervention
|Number of participants (arm)=6
|Drop-out=0
|Drop-out reasons=NA
|Intervention=Resveratrol
|Dosage and regime=Oral (suspension) of microparticular resveratrol (SRT501): 1 x 5,0 g daily for approximately 14 days (minimum of 10 and a maximum of 21 days before surgery)
|One-time application=No
|Duration in days=14
|Side Effects / Interactions=AEs possibly or probably attributable to agent intake: They were primarily of a gastrointestinal nature, including nausea and diarrhoea, and mild in grade (grade 1 NCI CTC v3.0). Other AEs included chills, lethargy, rash, skin irritation and vascular flushing, which resolved without sequelae.
|Order number=1
}}
{{Arm
|Arm type=Placebo
|Number of participants (arm)=3
|Drop-out=0
|Drop-out reasons=NA
|Intervention=Placebo
|Dosage and regime=Oral (suspension) of placebo 1 x daily for approximately 14 days (minimum of 10 and a maximum of 21 days before surgery)
|One-time application=No
|Duration in days=approximately 14
|Side Effects / Interactions=One case of lethargy in the placebo group, which was ongoing at follow-up. One case with diarrhoea.
|Order number=2
}}
{{Arm Overview}}
=Outcomes=

{{Outcome
|Outcome type=Others
|Outcome name=PK (Pharmacokinetics)
|Outcome specification=?
|Type of measurement=Blood Test
|Results during intervention=?
|Results after intervention=?
|Bias arising from the randomization process=?
|Bias due to deviation from intended intervention (assignment to intervention)=?
|Bias due to deviation from intended intervention (adhering to intervention)=NA
|Bias due to missing outcome data=?
|Bias in measurement of the outcome=?
|Bias in selection of the reported result=?
|Other sources of bias=?
|Overall RoB judgment=?
|Order number=1
}}
{{Outcome Overview}}
=Funding and Conflicts of Interest=

{{Funding and Conflicts of Interest
|Funding=Study was designed and sponsored by Sirtris
|Conflicts of Interest=According to authors no conflict of interest.
}}
=Further points for assessing the study=

{{Further points for assessing the study
|Samples sufficiently large=No
|power analysis performed=?
|reasons given for samples being too small according to power analysis=?
|Ethnicity mentioned=Yes
|Possibility of attention effects=NA
|Possibility of placebo effects=NA
|Other reasons=?
|Testing for normal distribution=?
|Correct application of statistical tests=?
|Correction for multiple testing=?
|Measurement of compliance=?
|Blinding reliable=?
|Check whether blinding was successful=?
|Consistent reporting in numbers=?
|sufficient washout period=?
|Tested for carry-over effects=?
|Were sequence effects tested=?
|Comprehensive and coherent reporting=?
|Were side effects systematically recorded=?
|Effect sizes reported=?
|Side effects taken into account in the interpretation of the results=?
|mono- or multicentric=?
|Ethics / CoI / Funding=?
}}
{{Additional Notes}}
=Additional Notes=

Howells et al. (2011): Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics

2024-08-08T09:59:05Z

CMensger:

{{Reference
|Reference=Publication: Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics
}}
{{Study Note}}
=Brief summary=
This study compared two groups of patients, all of whom had colorectal carcinoma (stage IV) with liver metastases and a life expectancy of more than 3 months. The patients received a resveratrol solution with micronized resveratrol (5.0 g) or a matching placebo once a day for approximately 14 days prior to surgical removal of the liver metastases. The purpose of the study was to assess the safety, pharmacokinetics and pharmacodynamics of the formulation (micronized resveratrol). The side effects were recorded in a daily diary according to fixed criteria. The two groups were comparable before treatment. Various side effects occurred, especially diarrhea, but the side effects were predominantly mild (grade 1). One patient discontinued the study due to diarrhea. One patient died after surgery due to peritonitis and liver failure, which, according to the study director, was not caused by resveratrol. The authors conclude that a 14-day intake of resveratrol (5.0 g) is well tolerated in colorectal cancer patients.

In dieser Studie wurden zwei Gruppen von Patienten miteinander verglichen, welche alle ein kolorektales Karzinom (Stadium IV) mit Lebermetastasen und eine Lebenserwartung von mehr als 3 Monaten hatten. Die Patienten haben ungefähr 14 Tage vor der operativen Entfernung der Lebermetastasen täglich eine Resveratrol-Lösung (5,0 g) oder ein passendes Placebo bekommen. Ziel der Studie war es, die Sicherheit, Pharmakokinetik und Pharmakodynamik der Formulierung (mikronisiertes Resveratrol) zu bewerten.Die Nebenwirkungen wurden mittels täglicher Tagebuchführung nach festen Kriterien erhoben. Die beiden Gruppen waren vor der Behandlung vergleichbar. Es traten verschiedene Nebenwirkungen v.a. Durchfall auf, allerdings waren die Nebenwirkungen überwiegend mild ausgeprägt (Grad 1). Ein Patient brach die Studie wegen Durchfall ab. Ein Patient starb nach der OP an einer Bauchfellentzündung und Leberversagen, was aber laut des Studienleiters nicht durch Resveratrol verursacht war. Die Autoren schließen, dass eine 14 tägige Einnahme von Resveratrol (5,0 g) bei Darmkrebspatienten gut verträglich ist.

=Study Design=

{{Study Design (RCT)
|Perspective=Prospective
|Centralized=Multicentric
|Blinding=Double
|Is randomized=Yes
|Cross-over=No
|Number of arms=2
}}
=Study characteristics=

{{RCT study general properties
|Inclusion criteria=Subjects (18 years or older) presenting with confirmed stage IV colorectal cancer and hepatic metastases, who had not received therapeutic intervention for their cancer within 6 weeks of study commencement and had a life expectancy of >3 months, were recruited into the study. All patients were due to undergo resection of liver metastases. Participants had to be physically capable of complying with the protocol and had a normal ECG and no history of HIV or hepatitis B/C.
|Exclusion criteria=Patient were asked to refrain from large quantities of resveratrol-containing foods and drinks such as peanuts, grapes, mulberries and alcohol within 48 h of scheduled PK collection days, and the day of surgical resection.
|N randomized=9
|Analysis=?
|Specifications on analyses=All nine subjects were analysed. This is a Phase I study about safety, pharmapharmacokinetics, pharmacodynamics and not an efficacy study.
PK: Statistical analyses for pharmacokinetic data included linear regression with 1/concentration weighting and descriptive statistics.
PD: Means were compared via one way, one sided ANOVA followed by Tukey’s post hoc test.
|Countries of data collection=United Kingdom
|LoE=2b Oxford 2009
|Outcome timeline=Patients ingested the formulation pre-operatively daily for a minimum of 10 and a maximum of 21 days, dependent upon surgical scheduling. Plasma samples for PK assessment were obtained on days 1 and 2, and on the day of surgical resection. Plasma for PD assessment was obtained pre-dose, immediately prior to, and during surgery. Diseased and normal adjacent hepatic tissue was resected 6-7 h after the last dose.
}}
=Characteristics of participants=

{{Characteristics of participants
|Setting=Palliative
|Types of cancer=Colorectal Cancer
|Stage cancer=Advanced Stage
|Cancer stage specification=Stage IV colorectal cancer and hepatic metastases
|Comorbidity=NI
|Current cancer therapy=Surgery
|Specifications on cancer therapies=Resection of liver metastases
|Previous cancer therapies=NI
|Gender=Mixed
|Gender specifications=SRT501 (resveratrol): Male (5), female (1)
Placebo: Male (1), female (2)
|Age groups=Adults (18+)
|Age groups specification=SRT501 (resveratrol): 68.5(10.8) years
Placebo: 64.3(6.35) years
}}
=Arms=

{{Arm
|Arm type=Intervention
|Number of participants (arm)=6
|Drop-out=0
|Drop-out reasons=NA
|Intervention=Resveratrol
|Dosage and regime=Oral (suspension) of microparticular resveratrol (SRT501): 1 x 5,0 g daily for approximately 14 days (minimum of 10 and a maximum of 21 days before surgery)
|One-time application=No
|Duration in days=14
|Side Effects / Interactions=AEs possibly or probably attributable to agent intake: They were primarily of a gastrointestinal nature, including nausea and diarrhoea, and mild in grade (grade 1 NCI CTC v3.0). Other AEs included chills, lethargy, rash, skin irritation and vascular flushing, which resolved without sequelae.
|Order number=1
}}
{{Arm
|Arm type=Placebo
|Number of participants (arm)=3
|Drop-out=0
|Drop-out reasons=NA
|Intervention=Placebo
|Dosage and regime=Oral (suspension) of placebo 1 x daily for approximately 14 days (minimum of 10 and a maximum of 21 days before surgery)
|One-time application=No
|Duration in days=14
|Side Effects / Interactions=One case of lethargy in the placebo group, which was ongoing at follow-up. One case with diarrhoea.
|Order number=2
}}
{{Arm Overview}}
=Outcomes=

{{Outcome
|Outcome type=Others
|Outcome name=PK (Pharmacokinetics)
|Outcome specification=?
|Type of measurement=Blood Test
|Results during intervention=?
|Results after intervention=?
|Bias arising from the randomization process=?
|Bias due to deviation from intended intervention (assignment to intervention)=?
|Bias due to deviation from intended intervention (adhering to intervention)=NA
|Bias due to missing outcome data=?
|Bias in measurement of the outcome=?
|Bias in selection of the reported result=?
|Other sources of bias=?
|Overall RoB judgment=?
|Order number=1
}}
{{Outcome Overview}}
=Funding and Conflicts of Interest=

{{Funding and Conflicts of Interest
|Funding=Study was designed and sponsored by Sirtris
|Conflicts of Interest=According to authors no conflict of interest.
}}
=Further points for assessing the study=

{{Further points for assessing the study
|Samples sufficiently large=No
|power analysis performed=?
|reasons given for samples being too small according to power analysis=?
|Ethnicity mentioned=Yes
|Possibility of attention effects=NA
|Possibility of placebo effects=NA
|Other reasons=?
|Testing for normal distribution=?
|Correct application of statistical tests=?
|Correction for multiple testing=?
|Measurement of compliance=?
|Blinding reliable=?
|Check whether blinding was successful=?
|Consistent reporting in numbers=?
|sufficient washout period=?
|Tested for carry-over effects=?
|Were sequence effects tested=?
|Comprehensive and coherent reporting=?
|Were side effects systematically recorded=?
|Effect sizes reported=?
|Side effects taken into account in the interpretation of the results=?
|mono- or multicentric=?
|Ethics / CoI / Funding=?
}}
{{Additional Notes}}
=Additional Notes=

Howells et al. (2011): Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics

2024-08-08T09:54:47Z

CMensger:

{{Reference
|Reference=Publication: Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics
}}
{{Study Note}}
=Brief summary=
This study compared two groups of patients, all of whom had colorectal carcinoma (stage IV) with liver metastases and a life expectancy of more than 3 months. The patients received a resveratrol solution with micronized resveratrol (5.0 g) or a matching placebo once a day for approximately 14 days prior to surgical removal of the liver metastases. The purpose of the study was to assess the safety, pharmacokinetics and pharmacodynamics of the formulation (micronized resveratrol). The side effects were recorded in a daily diary according to fixed criteria. The two groups were comparable before treatment. Various side effects occurred, especially diarrhea, but the side effects were predominantly mild (grade 1). One patient discontinued the study due to diarrhea. One patient died after surgery due to peritonitis and liver failure, which, according to the study director, was not caused by resveratrol. The authors conclude that a 14-day intake of resveratrol (5.0 g) is well tolerated in colorectal cancer patients.

In dieser Studie wurden zwei Gruppen von Patienten miteinander verglichen, welche alle ein kolorektales Karzinom (Stadium IV) mit Lebermetastasen und eine Lebenserwartung von mehr als 3 Monaten hatten. Die Patienten haben ungefähr 14 Tage vor der operativen Entfernung der Lebermetastasen täglich eine Resveratrol-Lösung (5,0 g) oder ein passendes Placebo bekommen. Ziel der Studie war es, die Sicherheit, Pharmakokinetik und Pharmakodynamik der Formulierung (mikronisiertes Resveratrol) zu bewerten.Die Nebenwirkungen wurden mittels täglicher Tagebuchführung nach festen Kriterien erhoben. Die beiden Gruppen waren vor der Behandlung vergleichbar. Es traten verschiedene Nebenwirkungen v.a. Durchfall auf, allerdings waren die Nebenwirkungen überwiegend mild ausgeprägt (Grad 1). Ein Patient brach die Studie wegen Durchfall ab. Ein Patient starb nach der OP an einer Bauchfellentzündung und Leberversagen, was aber laut des Studienleiters nicht durch Resveratrol verursacht war. Die Autoren schließen, dass eine 14 tägige Einnahme von Resveratrol (5,0 g) bei Darmkrebspatienten gut verträglich ist.

=Study Design=

{{Study Design (RCT)
|Perspective=Prospective
|Centralized=Multicentric
|Blinding=Double
|Is randomized=Yes
|Cross-over=No
|Number of arms=2
}}
=Study characteristics=

{{RCT study general properties
|Inclusion criteria=Subjects (18 years or older) presenting with confirmed stage IV colorectal cancer and hepatic metastases, who had not received therapeutic intervention for their cancer within 6 weeks of study commencement and had a life expectancy of >3 months, were recruited into the study. All patients were due to undergo resection of liver metastases. Participants had to be physically capable of complying with the protocol and had a normal ECG and no history of HIV or hepatitis B/C.
|Exclusion criteria=Patient were asked to refrain from large quantities of resveratrol-containing foods and drinks such as peanuts, grapes, mulberries and alcohol within 48 h of scheduled PK collection days, and the day of surgical resection.
|N randomized=9
|Analysis=?
|Specifications on analyses=All nine subjects were analysed. This is a Phase I study about safety, pharmapharmacokinetics, pharmacodynamics and not an efficacy study.
PK: Statistical analyses for pharmacokinetic data included linear regression with 1/concentration weighting and descriptive statistics.
PD: Means were compared via one way, one sided ANOVA followed by Tukey’s post hoc test.
|Countries of data collection=United Kingdom
|LoE=2b Oxford 2009
|Outcome timeline=Patients ingested the formulation pre-operatively daily for a minimum of 10 and a maximum of 21 days, dependent upon surgical scheduling. Plasma samples for PK assessment were obtained on days 1 and 2, and on the day of surgical resection. Plasma for PD assessment was obtained pre-dose, immediately prior to, and during surgery. Diseased and normal adjacent hepatic tissue was resected 6-7 h after the last dose.
}}
=Characteristics of participants=

{{Characteristics of participants
|Setting=Palliative
|Types of cancer=Colorectal Cancer
|Stage cancer=Advanced Stage
|Cancer stage specification=Stage IV colorectal cancer and hepatic metastases
|Comorbidity=NI
|Current cancer therapy=Surgery
|Specifications on cancer therapies=Resection of liver metastases
|Previous cancer therapies=NI
|Gender=Mixed
|Gender specifications=SRT501 (resveratrol): Male (5), female (1)
Placebo: Male (1), female (2)
|Age groups=Adults (18+)
|Age groups specification=SRT501 (resveratrol): 68.5(10.8) years
Placebo: 64.3(6.35) years
}}
=Arms=

{{Arm
|Arm type=Intervention
|Number of participants (arm)=6
|Drop-out=0
|Drop-out reasons=NA
|Intervention=Resveratrol
|Dosage and regime=Oral (suspension) of microparticular resveratrol (SRT501): 1 x 5,0 g daily for approximately 14 days (minimum of 10 and a maximum of 21 days before surgery)
|One-time application=No
|Duration in days=14
|Side Effects / Interactions=AEs possibly or probably attributable to agent intake: They were primarily of a gastrointestinal nature, including nausea and diarrhoea, and mild in grade (grade 1 NCI CTC v3.0). Other AEs included chills, lethargy, rash, skin irritation and vascular flushing, which resolved without sequelae.
|Order number=1
}}
{{Arm
|Arm type=Placebo
|Number of participants (arm)=3
|Drop-out=0
|Drop-out reasons=NA
|Intervention=Placebo
|Dosage and regime=Oral (suspension) of placebo 1 x daily for approximately 14 days (minimum of 10 and a maximum of 21 days before surgery)
|One-time application=No
|Duration in days=14
|Side Effects / Interactions=One case of lethargy in the placebo group, which was ongoing at follow-up. One case with diarrhoea.
|Order number=2
}}
{{Arm Overview}}
=Outcomes=

{{Outcome
|Outcome type=Others
|Outcome name=?
|Outcome specification=?
|Type of measurement=Blood Test
|Results during intervention=?
|Results after intervention=?
|Bias arising from the randomization process=?
|Bias due to deviation from intended intervention (assignment to intervention)=?
|Bias due to deviation from intended intervention (adhering to intervention)=NA
|Bias due to missing outcome data=?
|Bias in measurement of the outcome=?
|Bias in selection of the reported result=?
|Other sources of bias=?
|Overall RoB judgment=?
|Order number=1
}}
{{Outcome Overview}}
=Funding and Conflicts of Interest=

{{Funding and Conflicts of Interest
|Funding=Study was sponsored by Sirtris.
|Conflicts of Interest=According to authors no conflict of interest.
}}
=Further points for assessing the study=

{{Further points for assessing the study
|Samples sufficiently large=No
|power analysis performed=?
|reasons given for samples being too small according to power analysis=?
|Ethnicity mentioned=Yes
|Possibility of attention effects=NA
|Possibility of placebo effects=NA
|Other reasons=?
|Testing for normal distribution=?
|Correct application of statistical tests=?
|Correction for multiple testing=?
|Measurement of compliance=?
|Blinding reliable=?
|Check whether blinding was successful=?
|Consistent reporting in numbers=?
|sufficient washout period=?
|Tested for carry-over effects=?
|Were sequence effects tested=?
|Comprehensive and coherent reporting=?
|Were side effects systematically recorded=?
|Effect sizes reported=?
|Side effects taken into account in the interpretation of the results=?
|mono- or multicentric=?
|Ethics / CoI / Funding=?
}}
{{Additional Notes}}
=Additional Notes=

Howells et al. (2011): Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics

2024-08-08T09:17:45Z

CMensger:

{{Reference
|Reference=Publication: Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics
}}
{{Study Note}}
=Brief summary=
This study compared two groups of patients, all of whom had colorectal carcinoma (stage IV) with liver metastases and a life expectancy of less than 3 months. The patients received a resveratrol solution (5.0 g) or a matching placebo once a day for 14 days prior to surgical removal of the liver metastases. Various laboratory values and the side effects of resveratrol were recorded in a daily diary according to fixed criteria. The two groups were comparable before treatment. Various side effects occurred, especially diarrhea, but the side effects were predominantly mild (grade 1). One patient discontinued the study due to diarrhea. One patient died after surgery due to peritonitis and liver failure, which, according to the study director, was not caused by resveratrol. The authors conclude that a 14-day intake of resveratrol (5.0 g) is well tolerated in colorectal cancer patients. However, the sample was very small, so the results cannot be generalized.

In dieser Studie wurden zwei Gruppen von Patienten miteinander verglichen, welche alle ein kolorektales Karzinom (Stadium IV) mit Lebermetastasen und eine Lebenserwartung von mehr als 3 Monaten hatten. Die Patienten haben 14 Tage vor der operativen Entfernung der Lebermetastasen täglich eine Resveratrol-Lösung (5,0 g) oder ein passendes Placebo bekommen. Es wurden verschiedene Laborwerte und die Nebenwirkungen von Resveratrol mittels täglicher Tagebuchführung nach festen Kriterien erhoben. Die beiden Gruppen waren vor der Behandlung vergleichbar. Es traten verschiedene Nebenwirkungen v.a. Durchfall auf, allerdings waren die Nebenwirkungen überwiegend mild ausgeprägt (Grad 1). Ein Patient brach die Studie wegen Durchfall ab. Ein Patient starb nach der OP an einer Bauchfellentzündung und Leberversagen, was aber laut des Studienleiters nicht durch Resveratrol verursacht war. Die Autoren schließen, dass eine 14 tägige Einnahme von Resveratrol (5,0 g) bei Darmkrebspatienten gut verträglich ist. Allerdings war die Stichprobe sehr klein, so dass die Ergebnisse nicht zu verallgemeinern sind.

=Study Design=

{{Study Design (RCT)
|Perspective=Prospective
|Centralized=Multicentric
|Blinding=Double
|Is randomized=Yes
|Cross-over=No
|Number of arms=2
}}
=Study characteristics=

{{RCT study general properties
|Inclusion criteria=Subjects (18 years or older) presenting with confirmed stage IV colorectal cancer and hepatic metastases, who had not received therapeutic intervention for their cancer within 6 weeks of study commencement and had a life expectancy of >3 months, were recruited into the study. All patients were due to undergo resection of liver metastases. Participants had to be physically capable of complying with the protocol and had a normal ECG and no history of HIV or hepatitis B/C.
|Exclusion criteria=Patient were asked to refrain from large quantities of resveratrol-containing foods and drinks such as peanuts, grapes, mulberries and alcohol within 48 h of scheduled PK collection days, and the day of surgical resection.
|N randomized=9
|Analysis=?
|Specifications on analyses=All nine subjects were analysed. This is a Phase I study about safety, pharmapharmacokinetics, pharmacodynamics and not an efficacy study.
PK: Statistical analyses for pharmacokinetic data included linear regression with 1/concentration weighting and descriptive statistics.
PD: Means were compared via one way, one sided ANOVA followed by Tukey’s post hoc test.
|Countries of data collection=United Kingdom
|LoE=2b Oxford 2009
|Outcome timeline=Patients ingested the formulation pre-operatively daily for a minimum of 10 and a maximum of 21 days, dependent upon surgical scheduling. Plasma samples for PK assessment were obtained on days 1 and 2, and on the day of surgical resection. Plasma for PD assessment was obtained pre-dose, immediately prior to, and during surgery. Diseased and normal adjacent hepatic tissue was resected 6-7 h after the last dose.
}}
=Characteristics of participants=

{{Characteristics of participants
|Setting=Palliative
|Types of cancer=Colorectal Cancer
|Stage cancer=Advanced Stage
|Cancer stage specification=Stage IV colorectal cancer and hepatic metastases
|Comorbidity=NI
|Current cancer therapy=Surgery
|Specifications on cancer therapies=Resection of liver metastases
|Previous cancer therapies=NI
|Gender=Mixed
|Gender specifications=SRT501 (resveratrol): Male (5), female (1)
Placebo: Male (1), female (2)
|Age groups=Adults (18+)
|Age groups specification=SRT501 (resveratrol): 68.5(10.8) years
Placebo: 64.3(6.35) years
}}
=Arms=

{{Arm
|Arm type=Intervention
|Number of participants (arm)=6
|Drop-out=0
|Drop-out reasons=NA
|Intervention=Resveratrol
|Dosage and regime=Oral (suspension) of microparticular resveratrol (SRT501): 1 x 5,0 g daily for approximately 14 days (minimum of 10 and a maximum of 21 days before surgery)
|One-time application=No
|Duration in days=14
|Side Effects / Interactions=AEs possibly or probably attributable to agent intake: They were primarily of a gastrointestinal nature, including nausea and diarrhoea, and mild in grade (grade 1 NCI CTC v3.0). Other AEs included chills, lethargy, rash, skin irritation and vascular flushing, which resolved without sequelae.
|Order number=1
}}
{{Arm
|Arm type=Placebo
|Number of participants (arm)=3
|Drop-out=0
|Drop-out reasons=NA
|Intervention=Placebo
|Dosage and regime=Oral (suspension) of placebo 1 x daily for approximately 14 days (minimum of 10 and a maximum of 21 days before surgery)
|One-time application=No
|Duration in days=14
|Side Effects / Interactions=One case of lethargy in the placebo group, which was ongoing at follow-up. One case with diarrhoea.
|Order number=2
}}
{{Arm Overview}}
=Outcomes=

{{Outcome
|Outcome type=Others
|Outcome name=?
|Outcome specification=?
|Type of measurement=Blood Test
|Results during intervention=?
|Results after intervention=?
|Bias arising from the randomization process=?
|Bias due to deviation from intended intervention (assignment to intervention)=?
|Bias due to deviation from intended intervention (adhering to intervention)=NA
|Bias due to missing outcome data=?
|Bias in measurement of the outcome=?
|Bias in selection of the reported result=?
|Other sources of bias=?
|Overall RoB judgment=?
|Order number=1
}}
{{Outcome Overview}}
=Funding and Conflicts of Interest=

{{Funding and Conflicts of Interest
|Funding=Study was sponsored by Sirtris.
|Conflicts of Interest=According to authors no conflict of interest.
}}
=Further points for assessing the study=

{{Further points for assessing the study
|Samples sufficiently large=No
|power analysis performed=?
|reasons given for samples being too small according to power analysis=?
|Ethnicity mentioned=Yes
|Possibility of attention effects=NA
|Possibility of placebo effects=NA
|Other reasons=?
|Testing for normal distribution=?
|Correct application of statistical tests=?
|Correction for multiple testing=?
|Measurement of compliance=?
|Blinding reliable=?
|Check whether blinding was successful=?
|Consistent reporting in numbers=?
|sufficient washout period=?
|Tested for carry-over effects=?
|Were sequence effects tested=?
|Comprehensive and coherent reporting=?
|Were side effects systematically recorded=?
|Effect sizes reported=?
|Side effects taken into account in the interpretation of the results=?
|mono- or multicentric=?
|Ethics / CoI / Funding=?
}}
{{Additional Notes}}
=Additional Notes=

Howells et al. (2011): Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics

2024-07-11T11:50:17Z

CMensger:

{{Reference
|Reference=Publication: Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics
}}
{{Study Note}}
=Brief summary=
This study compared two groups of patients, all of whom had colorectal carcinoma (stage IV) with liver metastases and a life expectancy of less than 3 months. The patients received a resveratrol solution (5.0 g) or a matching placebo once a day for 14 days prior to surgical removal of the liver metastases. Various laboratory values and the side effects of resveratrol were recorded in a daily diary according to fixed criteria. The two groups were comparable before treatment. Various side effects occurred, especially diarrhea, but the side effects were predominantly mild (grade 1). One patient discontinued the study due to diarrhea. One patient died after surgery due to peritonitis and liver failure, which, according to the study director, was not caused by resveratrol. The authors conclude that a 14-day intake of resveratrol (5.0 g) is well tolerated in colorectal cancer patients. However, the sample was very small, so the results cannot be generalized.

In dieser Studie wurden zwei Gruppen von Patienten miteinander verglichen, welche alle ein kolorektales Karzinom (Stadium IV) mit Lebermetastasen und eine Lebenserwartung von mehr als 3 Monaten hatten. Die Patienten haben 14 Tage vor der operativen Entfernung der Lebermetastasen täglich eine Resveratrol-Lösung (5,0 g) oder ein passendes Placebo bekommen. Es wurden verschiedene Laborwerte und die Nebenwirkungen von Resveratrol mittels täglicher Tagebuchführung nach festen Kriterien erhoben. Die beiden Gruppen waren vor der Behandlung vergleichbar. Es traten verschiedene Nebenwirkungen v.a. Durchfall auf, allerdings waren die Nebenwirkungen überwiegend mild ausgeprägt (Grad 1). Ein Patient brach die Studie wegen Durchfall ab. Ein Patient starb nach der OP an einer Bauchfellentzündung und Leberversagen, was aber laut des Studienleiters nicht durch Resveratrol verursacht war. Die Autoren schließen, dass eine 14 tägige Einnahme von Resveratrol (5,0 g) bei Darmkrebspatienten gut verträglich ist. Allerdings war die Stichprobe sehr klein, so dass die Ergebnisse nicht zu verallgemeinern sind.

=Study Design=

{{Study Design (RCT)
|Perspective=Prospective
|Centralized=Multicentric
|Blinding=Double
|Is randomized=Yes
|Cross-over=No
|Number of arms=2
}}
=Study characteristics=

{{RCT study general properties
|Inclusion criteria=Subjects (18 years or older) presenting with confirmed stage IV colorectal cancer and hepatic metastases, who had not received therapeutic intervention for their cancer within 6 weeks of study commencement and had a life expectancy of >3 months, were recruited into the study. All patients were due to undergo resection of liver metastases. Participants had to be physically capable of complying with the protocol and had a normal ECG and no history of HIV or hepatitis B/C.
|Exclusion criteria=Patient were asked to refrain from large quantities of resveratrol-containing foods and drinks such as peanuts, grapes, mulberries and alcohol within 48 h of scheduled PK collection days, and the day of surgical resection.
|N randomized=9
|Analysis=?
|Specifications on analyses=All nine subjects were analysed. This is a Phase I study about safety, pharmapharmacokinetics, pharmacodynamics and not an efficacy study.
PK: Statistical analyses for pharmacokinetic data included linear regression with 1/concentration weighting and descriptive statistics.
PD: Means were compared via one way, one sided ANOVA followed by Tukey’s post hoc test.
|Countries of data collection=United Kingdom
|LoE=2b Oxford 2009
|Outcome timeline=Patients ingested the formulation pre-operatively daily for a minimum of 10 and a maximum of 21 days, dependent upon surgical scheduling. Plasma samples for PK assessment were obtained on days 1 and 2, and on the day of surgical resection. Plasma for PD assessment was obtained pre-dose, immediately prior to, and during surgery. Diseased and normal adjacent hepatic tissue was resected 6-7 h after the last dose.
}}
=Characteristics of participants=

{{Characteristics of participants
|Setting=?
|Types of cancer=Colorectal Cancer
|Stage cancer=Advanced Stage
|Cancer stage specification=Stage IV colorectal cancer and hepatic metastases
|Comorbidity=NI
|Current cancer therapy=Surgery
|Specifications on cancer therapies=Resection of liver metastases
|Previous cancer therapies=NI
|Gender=Mixed
|Gender specifications=SRT501 (resveratrol): Male (5), female (1)
Placebo: Male (1), female (2)
|Age groups=Adults (18+)
|Age groups specification=SRT501 (resveratrol): 68.5(10.8)
Placebo: 64.3(6.35)
}}
=Arms=

{{Arm
|Arm type=Intervention
|Number of participants (arm)=6
|Drop-out=0
|Drop-out reasons=NA
|Intervention=Resveratrol
|Dosage and regime=Oral (suspension) of microparticular resveratrol (SRT501): 1 x 5,0 g daily for approximately 14 days (minimum of 10 and a maximum of 21 days before surgery)
|One-time application=No
|Duration in days=14
|Side Effects / Interactions=AEs possibly or probably attributable to agent intake: They were primarily of a gastrointestinal nature, including nausea and diarrhoea, and mild in grade (grade 1 NCI CTC v3.0). Other AEs included chills, lethargy, rash, skin irritation and vascular flushing, which resolved without sequelae.
|Order number=1
}}
{{Arm
|Arm type=Placebo
|Number of participants (arm)=3
|Drop-out=0
|Drop-out reasons=NA
|Intervention=Placebo
|Dosage and regime=Oral (suspension) of placebo 1 x daily for approximately 14 days (minimum of 10 and a maximum of 21 days before surgery)
|One-time application=No
|Duration in days=14
|Side Effects / Interactions=One case of lethargy in the placebo group, which was ongoing at follow-up. One case with diarrhoea.
|Order number=2
}}
{{Arm Overview}}
=Outcomes=

{{Outcome
|Outcome type=Others
|Outcome name=?
|Outcome specification=?
|Type of measurement=Blood Test
|Results during intervention=?
|Results after intervention=?
|Bias arising from the randomization process=?
|Bias due to deviation from intended intervention (assignment to intervention)=?
|Bias due to deviation from intended intervention (adhering to intervention)=NA
|Bias due to missing outcome data=?
|Bias in measurement of the outcome=?
|Bias in selection of the reported result=?
|Other sources of bias=?
|Overall RoB judgment=?
|Order number=1
}}
{{Outcome Overview}}
=Funding and Conflicts of Interest=

{{Funding and Conflicts of Interest
|Funding=Study was sponsored by Sirtris.
|Conflicts of Interest=According to authors no conflict of interest.
}}
=Further points for assessing the study=

{{Further points for assessing the study
|Samples sufficiently large=No
|power analysis performed=?
|reasons given for samples being too small according to power analysis=?
|Ethnicity mentioned=Yes
|Possibility of attention effects=NA
|Possibility of placebo effects=NA
|Other reasons=?
|Testing for normal distribution=?
|Correct application of statistical tests=?
|Correction for multiple testing=?
|Measurement of compliance=?
|Blinding reliable=?
|Check whether blinding was successful=?
|Consistent reporting in numbers=?
|sufficient washout period=?
|Tested for carry-over effects=?
|Were sequence effects tested=?
|Comprehensive and coherent reporting=?
|Were side effects systematically recorded=?
|Effect sizes reported=?
|Side effects taken into account in the interpretation of the results=?
|mono- or multicentric=?
|Ethics / CoI / Funding=?
}}
{{Additional Notes}}
=Additional Notes=

Howells et al. (2011): Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics

2024-07-11T11:48:46Z

CMensger:

Howells et al. (2011): Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics

2024-07-11T11:23:55Z

CMensger:

Howells et al. (2011): Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics

2024-07-11T10:57:41Z

CMensger:

Howells et al. (2011): Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics

2024-07-11T10:06:18Z

CMensger:

Howells et al. (2011): Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics

2024-07-11T10:03:54Z

CMensger:

Howells et al. (2011): Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics

2024-07-11T09:52:18Z

CMensger:

Howells et al. (2011): Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics

2024-07-11T09:47:51Z

CMensger:

Howells et al. (2011): Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics

2024-07-11T09:45:48Z

CMensger:

Howells et al. (2011): Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics

2024-07-11T08:28:42Z

CMensger:

Howells et al. (2011): Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics

2024-07-11T08:13:52Z

CMensger:

Howells et al. (2011): Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics

2024-07-11T08:08:56Z

CMensger:

Howells et al. (2011): Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics

2024-07-11T07:58:59Z

CMensger:

Howells et al. (2011): Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics

2024-07-11T07:46:08Z

CMensger:

Howells et al. (2011): Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics

2024-07-11T07:38:10Z

CMensger:

{{Reference
|Reference=Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics
}}
{{Study Note}}
=Brief summary=
This study compared two groups of patients, all of whom had colorectal carcinoma (stage IV) with liver metastases and a life expectancy of less than 3 months. The patients received a resveratrol solution (5.0 g) or a matching placebo once a day for 14 days prior to surgical removal of the liver metastases. Various laboratory values and the side effects of resveratrol were recorded in a daily diary according to fixed criteria. The two groups were comparable before treatment. Various side effects occurred, especially diarrhea, but the side effects were predominantly mild (grade 1). One patient discontinued the study due to diarrhea. One patient died after surgery due to peritonitis and liver failure, which, according to the study director, was not caused by resveratrol. The authors conclude that a 14-day intake of resveratrol (5.0 g) is well tolerated in colorectal cancer patients. However, the sample was very small, so the results cannot be generalized.

In dieser Studie wurden zwei Gruppen von Patienten miteinander verglichen, welche alle ein kolorektales Karzinom (Stadium IV) mit Lebermetastasen und eine Lebenserwartung von weniger als 3 Monaten hatten. Die Patienten haben 14 Tage vor der operativen Entfernung der Lebermetastasen einmal am Tag eine Resveratrol-Lösung (5,0 g) oder ein passendes Placebo bekommen. Es wurden verschiedene Laborwerte und die Nebenwirkungen von Resveratrol mittels täglicher Tagebuchführung nach festen Kriterien erhoben. Die beiden Gruppen waren vor der Behandlung vergleichbar. Es traten verschiedene Nebenwirkungen v.a. Durchfall auf, allerdings waren die Nebenwirkungen überwiegend mild ausgeprägt (Grad 1). Ein Patient brach die Studie wegen Durchfall ab. Ein Patient starb nach der OP an einer Bauchfellentzündung und Leberversagen, was aber laut des Studienleiters nicht durch Resveratrol verursacht war. Die Autoren schließen, dass eine 14 tägige Einnahme von Resveratrol (5,0 g) bei Darmkrebspatienten gut verträglich ist. Allerdings war die Stichprobe sehr klein, so dass die Ergebnisse nicht zu verallgemeinern sind.

=Study Design=

{{Study Design (RCT)
|Perspective=Prospective
|Centralized=Multicentric
|Blinding=Double
|Is randomized=Yes
|Cross-over=No
|Number of arms=2
}}
=Study characteristics=

{{RCT study general properties
|Inclusion criteria=?
|Exclusion criteria=?
|N randomized=9
|Analysis=?
|Specifications on analyses=?
|Countries of data collection=United Kingdom, ?
|LoE=2b Oxford 2009
|Outcome timeline=?
}}
=Characteristics of participants=

{{Characteristics of participants
|Setting=?
|Types of cancer=?
|Stage cancer=?
|Cancer stage specification=?
|Comorbidity=?
|Current cancer therapy=?
|Specifications on cancer therapies=?
|Previous cancer therapies=?
|Gender=?
|Gender specifications=?
|Age groups=Adults (18+)
|Age groups specification=?
}}
=Arms=

{{Arm Overview}}
=Outcomes=

{{Outcome Overview}}
=Funding and Conflicts of Interest=

{{Funding and Conflicts of Interest
|Funding=Study was sponsored by Sirtris.
|Conflicts of Interest=According to authors no conflict of interest.
}}
=Further points for assessing the study=

{{Further points for assessing the study
|Samples sufficiently large=No
|power analysis performed=?
|reasons given for samples being too small according to power analysis=?
|Ethnicity mentioned=?
|Possibility of attention effects=?
|Possibility of placebo effects=?
|Other reasons=?
|Testing for normal distribution=?
|Correct application of statistical tests=?
|Correction for multiple testing=?
|Measurement of compliance=?
|Blinding reliable=?
|Check whether blinding was successful=?
|Consistent reporting in numbers=?
|sufficient washout period=?
|Tested for carry-over effects=?
|Were sequence effects tested=?
|Comprehensive and coherent reporting=?
|Were side effects systematically recorded=?
|Effect sizes reported=?
|Side effects taken into account in the interpretation of the results=?
|mono- or multicentric=?
|Ethics / CoI / Funding=?
}}
{{Additional Notes}}
=Additional Notes=

Gescher, AJ

2024-06-20T07:35:16Z