Da Costa et al. (2009): Effectiveness of Guarana (Paullinia cupana) for Postradiation Fatigue and Depression Results of a Pilot Double-Blind Randomized Study

Reference ↗
Title	Effectiveness of Guarana (Paullinia cupana) for Postradiation Fatigue and Depression Results of a Pilot Double-Blind Randomized Study
Topic	Guarana
Author	da Costa Miranda, V, Trufelli, DC, Santos, J, Paschoin Campos, M, Nobuo, M, da Costa Miranda, M, Schlinder, F, Riechelmann, R, del Giglio, A
Year	2009
Journal	The journal of alternative and complementary medicine
DOI	https://doi.org/10.1089/acm.2008.0324

Brief summary

Similar to the study described above, researchers in this study also investigated the effect of guarana on chemotherapy-induced fatigue in patients with breast cancer. For 14 days, half of the women were asked to take guarana once a day, while the other half took a placebo. Patients then switched treatments for another 21 days (i.e. those who took guarana then took the placebo and those who took the placebo then took the guarana). Researchers found no differences in fatigue or depression between women taking guarana or placebo.

Ähnliche wie die oben beschriebene Studie haben Forscher in dieser Studie auch die Wirkung von Guarana auf eine Chemotherapie bedingte Fatigue bei Patienten mit Brustkrebs untersucht. 14 Tage lang wurde die Hälfte der Frauen gebeten, Guarana einmal täglich einzunehmen, während die andere Hälfte ein Placebo einnahm. Danach haben Patienten die Behandlung für weitere 21 Tage gewechselt (d.h. diejenigen, die Guarana einnahmen, nahmen dann das Placebo ein und diejenigen, die das Placebo einnahmen, nahmen dann den Guarana ein). Forscher fanden keine Unterschiede in der Fatigue oder Depression zwischen Frauen, die Guarana einnahmen oder Placebo einnahmen.

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	Prospective
Monocentric / Multicentric Monocentric: conducted in one center/ hospital; </br>Multicentric: conducted in multiple centers/ hospitals	Monocentric
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	Patients with a histological diagnosis of early stage breast cancer in an early stage (I or II) for whom adjuvant radiation therapy was indicated
Exclusion criteria	Patients with a previous history of radiation therapy, anemia, or clinical depression. Patients who were unable to grant informed consent or those who had medical contraindindications for the use of guarana (because of its psychostimulant effect) such as uncontrolled hypertension)
N randomized	36
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.	NI
Specifications on analyses	ANOVA
Countries of data collection	Brazil
LoE Level of evidence	2b Oxford 2009
Outcome timeline Data collection times	T0: Day 0, immediately before the first radiation treatment T1: Day 14, switching phase T2: Day 28, right before the start of the last radiation treatment

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, Adjuvant
Types of cancer "Other Cancers" means that only a subpopulation was specified, but further unspecified cancer types were included	Breast 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	Early Stage, Advanced Stage
Specifications on cancer stages	Early stage I or II
Comorbidities	NI
Current cancer therapies	Radiation therapy
Specifications on cancer therapies	NI
Previous cancer therapies	NI
Gender	Female
Gender specifications	100 % female
Age groups	Adults (18+)
Age groups specification	Average age of arm intervention-placebo = 59 years Average age of arm placebo-intervention = 57 years

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	NI
Drop-out reasons	NI
Intervention	75 mg of guayana extract
Dosage and regime	Daily for 14 days Cross-over: 14 days of placebo
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.	14
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	19
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	NI
Drop-out reasons	NI
Intervention	placebo
Dosage and regime	Daily for 14 days Cross-over: 75 mg of guayana extract daily for 14 days
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.	14
Side effects / Interactions	NI

Outcomes

Depression

Outcome type As specificed by the authors	Primary
Outcome specification
Type of measurement	BDI (Beck Depression Inventory)
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 differences between the arms were found. Arm intervention-placebo: After day 14: p = 0.51 Arm placebo-intervention: After day 14: p = 0.49 Comparison between both arms: Phase 1: p = .99 Phase 2: p = .97 Phase 3: 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	?

Fatigue

Outcome type As specificed by the authors	Primary
Outcome specification	NA
Type of measurement	BFI (Brief Fatigue Inventory)
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 between the arms were found. Arm intervention-placebo: After day 14: p = 0.52 Arm placebo-intervention: After day 14: p = 0.15 Comparison between both arms: Phase 1: p = . 24 Phase 2: p = .37 Phase 3: p = .39

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	The authors state that no competing financial interests exist.
Conflicts of Interest	No conflicts of interests were reported.

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	?