Del Giglio (2013): Purified Dry Extract of Paullinia cupana (Guarana) (PC-18) for Chemotherapy-Related Fatigue in Patients with Solid Tumors: An Early Discontinuation Study

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Title	Purified Dry Extract of Paullinia cupana (Guarana) (PC-18) for Chemotherapy-Related Fatigue in Patients with Solid Tumors: An Early Discontinuation Study
Topic	Guarana
Author	Braz del Giglio, A, de Iracema Gomes Cubero, D, Goberstein Lerner, T, Tuma Guariento, R, Guise Soares de Azevedo, R, Paiva, H, Goldman, C, Carelli, B, Melo Cruz, F, Schindler, F, Pianowski, L, Luongo de Matos, L, del Giglio, A
Year	2013
Journal	Journal of Dietary Supplements
DOI	https://doi.org/10.3109/19390211.2013.830676

Brief summary

In this study, researchers investigated the effect of guarana on patients with different types of cancer who suffered from fatigue after chemotherapy. After a three-week induction phase in which all patients received guarana, those who responded to the treatment were subsequently randomized to receive either guarana (2x/day 37.5mg) or placebo for 3 weeks. At the end of the randomized treatment phase, there were no differences in fatigue, depression or sleep quality.

In dieser Studie untersuchten Forscher die Wirkung von Guarana auf Patienten mit verschiedenen Arten von Krebs, die nach einer Chemotherapie an Fatigue litten. Nach einer dreiwöchigen Induktionsphase, in der alle Patienten Guarana erhielten, wurde diejenigen, die auf die Behandlung ansprachen, im Folgenden randomisiert, und erhielten 3 Wochen entweder Guarana (2x/Tag 37,5mg) oder Placebo. Am Ende der randomisierten Behandlungsphase fanden sich keine Unterschiede hinsichtlich Fatigue, Depression oder Schlafqualität.

Study Design

Prospective / Retrospective Prospective: forward-looking, examples include clinical trials, cohort studies, and long-term observational studies;</br>Retrospective: backward-looking, relying on existing data, examples include case-control studies and retrospective cohort studies	NI
Monocentric / Multicentric Monocentric: conducted in one center/ hospital; </br>Multicentric: conducted in multiple centers/ hospitals	Multicentric
Blinding No: Open, all parties are aware of group assignments;</br>Single: one party is unaware of group assignments (generally participants);</br>Double: two parties are unaware of group assignments (generally the participants and the researchers); </br>Triple: concealing group assignment from additional parties	Double
Is randomized	Yes
Cross-over Participants alternate between different treatment groups or conditions over a specified period, allowing each participant to serve as their own control	Yes
Number of arms	2

Study characteristics

Inclusion criteria	Adults with a histological diagnosis of cancer at any stage who were receiving systemic chemotherapy.
Exclusion criteria	Patients with a history of hypothyroidism, depression, or any other psychiatric disorder, anemia, prior antineoplastic treatment, or the inability to understand and sign an informed consent form. Patients who could be harmed by the stimulating properties of guarana, such as those with a history of insomnia, angina, or any cardiovascular disease, uncontrolled hypertension, or neurologic disorders.
N randomized	33
Analysis PP: Per Protocol analysis, i.e. only participants included who adhered to the study protocol.</br>ITT: Intention-to-treat analysis, i.e. all randomized participants included regardless of any drop-outs or changes in assignment.</br>mITT: modified Intention-to-treat analysis can refer to analyses in which participants with missing outcome data are excluded or it can refer to analyses in which only participants who received at least one treatment dose are included. In this case, participants dropped out of the study prematurely for reasons unrelated to the treatment.	PP Analysis
Specifications on analyses	Paired t-test
Countries of data collection	Brazil
LoE Level of evidence	2b Oxford 2009
Outcome timeline Data collection times	T0: Baseline, chemotherapy T1: After 3 weeks (after induction) T2: After 6 weeks (maintenance phase)

Characteristics of participants

Setting Refers to cancer therapy setting.</br>- Curative therapy: aims to completely eradicate a disease and achieve a full recovery; </br>- Neo-adjuvant therapy: form of curative therapy, given before the primary treatment for cancer (usually surgery); </br>- Adjuvant therapy: form of curative therapy, given after the primary treatment for cancer (usually surgery); </br>- Palliative therapy: focuses on providing relief from symptoms and improving the quality of life for patients, without necessarily targeting the underlying disease; </br>- Active surveillance: involves close monitoring of disease progression without any intervention (typically used for prostate cancer);</br>- No therapy setting: Patients who completed therapy/are currently not in cancer treatment, cancer survivors.	Curative
Types of cancer "Other Cancers" means that only a subpopulation was specified, but further unspecified cancer types were included	Breast Cancer, Colorectal Cancer, Gynecologic Cancers - Ovarian Cancer, Head and Neck Cancers, Lung Cancer
Cancer stages Early Stage: generally refers to cancer that is localized to the area where it started, mostly stages I and II;</br>Advanced Stage: cancer that has spread beyond its original site, mostly stages III and IV, with stage IV indicating distant metastasis	NI
Specifications on cancer stages	Cancer at any stages
Comorbidities	NI
Current cancer therapies	Chemotherapy
Specifications on cancer therapies	Systemic chemotherapy
Previous cancer therapies	NI
Gender	Mixed
Gender specifications	57.5 % female 42.5 % male
Age groups	Adults (18+)
Age groups specification	Mean (SD): 55.9 years (13.0)

Arms

Arm type Active control: group receives active treatment; </br>Passive control: for example treatment as usual, waiting control, no treatment	Intervention
Number of participants (arm) N randomized	17
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	1
Drop-out reasons	Absent at follow-up after randomization
Intervention	Paullinia cupana (PGUR0062F), purified extract
Dosage and regime	37.5 mg by mouth, 2x/day Starting after 1 week of chemotherapy, for 3 weeks Depending on the improvement or stabilization of the BFI scores: randomized assignment to either the continuation of PC-18 at the same dose
One-time application	No
Duration in days For long-term interventions, the number of days is an estimation.</br>A value of -999 indicates that the exact duration cannot be extracted from the study due to ambiguous or incomplete information. See Outcome timeline or Dosage and regime for further information.	42
Side effects / Interactions	NI

Arm type Active control: group receives active treatment; </br>Passive control: for example treatment as usual, waiting control, no treatment	Placebo
Number of participants (arm) N randomized	16
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	2
Drop-out reasons	Absent at follow-up after randomization
Intervention	Paullinia cupana (PGUR0062F), purified extract After 3 weeks: placebo
Dosage and regime	37.5 mg by mouth, 2x/day Starting after 1 week of chemotherapy, for 3 weeks Depending on the improvement or stabilization of the BFI scores: randomized assignment to a placebo for another 3 weeks
One-time application	No
Duration in days For long-term interventions, the number of days is an estimation.</br>A value of -999 indicates that the exact duration cannot be extracted from the study due to ambiguous or incomplete information. See Outcome timeline or Dosage and regime for further information.	42
Side effects / Interactions	NI

Outcomes

Fatigue

Outcome type As specificed by the authors	Primary
Outcome specification	NA
Type of measurement	FACIT (Functional Assessment of Chronic Illness Therapy)
Results during intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".	NA
Results after intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".	No significant difference between the arms. Comparison between the Placebo and Intervention Arm: After Day 42: p = .75

Risk of Bias Assessment: Cochrane RoB tool 2.0
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	?

Anxiety

Outcome type As specificed by the authors	Primary
Outcome specification	Anxiety and Depression
Type of measurement	HADS (Hospital Anxiety and Depression Scale)
Results during intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".	NA
Results after intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".	No significant difference between the arms. Comparison between the Placebo and Intervention Arm: After Day 42: HADS A: p = .75, HADS D: p = .94

Risk of Bias Assessment: Cochrane RoB tool 2.0
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	?

Sleep

Outcome type As specificed by the authors	Primary
Outcome specification	NA
Type of measurement	PSQI (Pittsburgh Sleep Quality Index)
Results during intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".	NA
Results after intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".	No significant difference between the arms. Comparison between the Placebo and Intervention Arm: After Day 42: p = .81

Risk of Bias Assessment: Cochrane RoB tool 2.0
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	?

Toxicity

Outcome type As specificed by the authors	Secondary
Outcome specification	2 instances of grade 3 toxicity in the intervention arm, which was not reported with placebo
Type of measurement	Observation
Results during intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".	NA
Results after intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".	1 Patient: depression 1 Patient: dizziness

Risk of Bias Assessment: Cochrane RoB tool 2.0
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	?

Funding and Conflicts of Interest

Funding	No information on funding.
Conflicts of Interest	The authors report no conflicts of interest Preparation was produced by the author himself.

Further points for assessing the study

Sample

Power analysis performed	?
- Sample size corresponds to power analysis
- Reasons for insufficient sample size based on power analysis
If no power analysis performed: at least moderate sample size (n >= 30 per arm)	?
Ethnicity mentioned	?

Alternative Explanation

Other explanations for an effect besides the investigated intervention
- Possibility of attention effects	?
- Possibility of placebo effects	?
- Other reasons	?

Statistics

Correct use of parametric and non-parametric tests Testing for normal distribution only necessary if parametric tests are used, NI: use of parametric tests without report of normal distribution testing
Correction for multiple testing	?
Measurement of compliance	?
Consistent reporting in numbers (figures, flowchart, abstract, results)	?
Comprehensive and coherent reporting	?
Cross-over
- Sufficient washout period	?
- Tested for carry-over effects	?
- Tested for sequence effects	?

Interpretation of results

Effect sizes reported (clinical vs. statistical significance)	?
Side effects systematically recorded	?
Side effects considered in result interpretation	?
Ethics votum	?