Ribeiro et al. (2017): Effects of zinc supplementation on fatigue and quality of life in patients with colorectal cancer

Reference ↗
Title	Effects of zinc supplementation on fatigue and quality of life in patients with colorectal cancer
Topic	Zinc
Author	Ribeiro, SMF, Braga, CBM, Peria, FM, Martinez, EZ, Rocha, JJR, Cunha, SFC
Year	2017
Journal	Einstein (Sao Paulo, Brazil)
DOI	https://dx.doi.org/10.1590/S1679-45082017AO3830

Brief summary

The study described was concerned with the administration of zinc to patients with colorectal cancer and its effect on fatigue/exhaustion and life satisfaction of the patients studied. The randomly divided sample was given either zinc or a placebo. It was found that the arms did not differ in the course of the parallel chemotherapy. When looking at the individual arms, it was found that the zinc arm did not change in their fatigue levels or in their life satisfaction. In the placebo arm, on the other hand, there was an increase in fatigue fatigue and a deterioration in life satisfaction from the first to the fourth cycle of therapy. The results suggest that zinc can protect against from worsening life satisfaction and fatigue in patients with colorectal cancer, however, due to the statistically insignificant difference between the statistically insignificant difference between the arms, no clear statement can be made. In addition, it must be critically considered that a very small sample was examined and it cannot be said with certainty that other factors besides zinc did not influence the result.

Die beschriebene Studie befasste sich mit der Gabe von Zink bei Patienten mit kolorektalem Karzinom und dessen Auswirkung auf Müdigkeit/ Erschöpfung und Lebenszufriedenheit der untersuchten Patienten. Die zufällig aufgeteilte Stichprobe bekam entweder Zink oder ein Placebo. Man fand heraus, dass sich die Arme im Verlauf der parallel stattfindenden Chemotherapie nicht unterschieden. Bei Betrachtung der einzelnen Arme zeigte sich, dass sich der Zink-Arm nicht in ihrem Fatigue-Wert und auch nicht in ihrer Lebenszufriedenheit veränderte. Im Placebo-Arm zeigten sich hingegen eine Zunahme der Fatigue und eine Verschlechterung der Lebenszufriedenheit vom ersten bis vierten Zyklus der Therapie. Die Ergebnisse legen nahe, dass Zink davor schützen kann, dass sich Lebenszufriedenheit und Fatigue bei Patienten mit kolorektalem Karzinom verschlechtert, allerdings kann aufgrund des statistisch nicht bedeutsamen Unterschieds zwischen den Armen keine eindeutige Aussage gemacht werden. Zudem ist kritisch zu betrachten, dass eine sehr kleine Stichprobe untersucht wurde und nicht mit Sicherheit gesagt werden kann, dass neben Zink nicht auch andere Faktoren das Ergebnis beeinflusst haben.

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	No
Number of arms	2

Study characteristics

Inclusion criteria	Undergone surgical resection of the colon or of rectal adenocarcinoma, and were on adjuvant or palliative treatment
Exclusion criteria	With liver, kidney, or chronic inflammatory autoimmune diseases; with active infectious diseases; who were undergoing therapy with immunosuppressants; who were on vitamin or mineral supplementation; who had been on chemo- or radiation therapy in the previous 12 months; and who had been diagnosed as cognitively impaired
N randomized	48
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
Countries of data collection	Brazil
LoE Level of evidence	2b Oxford 2009
Outcome timeline Data collection times	T0: baseline before the beginning of supplementation T1-T4: before each of the four cycles of chemotherapy

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, Palliative
Types of cancer "Other Cancers" means that only a subpopulation was specified, but further unspecified cancer types were included	Colorectal Cancer - Colon Cancer, Colorectal Cancer - Rectal 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	n=5 stage II, n=14 stage III, n=5 stage IV
Comorbidities	NI
Current cancer therapies	Chemotherapy
Specifications on cancer therapies	CAPOX (capecitabine + oxaliplatin) schedule; capecitabine; 5-fluorouracil and folinic acid
Previous cancer therapies	Surgery
Gender	Mixed
Gender specifications	Intervention arm: 4:6 (male: female) Placebo arm: 5:9 (male:female)
Age groups	Adults (18+)
Age groups specification	Intervention arm: mean (SD): 62.5 (7.5) Placebo arm: mean (SD): 63.8 (13.3)

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	24
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	14
Drop-out reasons	n=11 chemotherapy was not indicated, n=3 refused chemotherapy
Intervention	Zinc sulfate
Dosage and regime	Zinc sulfate (154mg/capsule), which corresponded to 35mg of elemental zinc, a capsule after breakfast and dinner, which amounted to 70mg of elemental zinc per day
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.	112
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	24
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	10
Drop-out reasons	n=9 chemotherapy was not indicated, n=1 refused chemotherapy
Intervention	Placebo
Dosage and regime	Placebo capsules, a capsule after breakfast and dinner
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.	112
Side effects / Interactions	NI

Outcomes

Fatigue

Outcome type As specificed by the authors	NI
Outcome specification	NI
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".	No significant differences between the groups over the 4 cycles
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".	NI

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	?

Quality of life

Outcome type As specificed by the authors	NI
Outcome specification	NI
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".	No significant differences between the groups over the 4 cycles
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".	NI

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	Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Grant #2011/07867-4 and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Grant #35046878860
Conflicts of Interest	NI

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	?