Zinc Supplementation on Markers of Oxidative Stress in Post Operative Colorectal Cancer During Chemotherapy Cycles

NCT02106806 | Completed

• 1 other identifier: FAPESP 2011/07867-4
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

Objective: To determine the oxidative stress during cycles of chemotherapy in patients after surgery for colorectal cancer, with or without oral zinc supplementation. Subjects: Twenty four adults from both genders participated in this study. All patients underwent stage II, III or IV colorectal cancer surgical resection and were starting chemotherapy in HCFMRP- USP. Patients were randomized into two groups. The first one (QTx-Zn Group, n=10) received 70 mg/d of zinc orally and the second one received placebo (QTx-Placebo Group, n=14) for 16 weeks. The study also included 30 healthy volunteers matched for age, gender and socioeconomic status, who received 70 mg/d of zinc supplement (Control-Zn Group, n=21) or placebo (Control-Placebo Group, n=9) for 16 weeks. Methods: The questionnaires about dietary intake (semiquantitative food frequency and food record), fatigue and quality of life (FACIT-F) and questionnaires that assess the side effects of chemotherapy (CTCAE) were evaluated. Anthropometry and bioelectrical impedance measurements were made. Blood collection was performed before the 1st, 2nd, 3rd and 4th cycles of chemotherapy (median duration of 21 days among cicles). Routine laboratory tests, vitamin E and markers anti and pro-oxidants (MDA, SOD, GPx and isoprostane) ere determined. The control group underwent the same procedures, except for chemotherapy. A longitudinal linear mixed effects model was adjusted for each of the variables of interest. The models were fitted using PROC MIXED of SAS version 9 (SAS, CARY, NC, USA). To analyze the association of categorical variables in the different items of the CTCAE, the investigators used the Fisher exact test. Results: The oral zinc supplementation was sufficient to increase plasma levels of zinc and did not alter food intake, body composition and routine laboratory evaluation of patients undergoing chemotherapy for colorectal cancer. Compared with QTx-Placebo Group, QTx-Zn Group showed lower prevalence of complaint on the salivary gland (17 vs. 75%). Fatigue (43 ± 6 vs. 36 ± 13) and quality of life (126 ± 160 vs. 116 ± 27) has become worst in the period between the 1st and 4th cycles of QTx in QTx-Placebo Group. When compared with QTx-Placebo Group, QTx-Zn Group had higher values of SOD before the 1st (2297 ± 503 vs. 1604 ± 352 USOD/g Hb), 2nd (2037 ± 515 vs. 1712 ± 417 USOD/g Hb) and 4th (2202 ± 323 vs. 1821 ± 360 USOD/g Hb) cycles of QTx. GPx values decreased in QTx-Zn Group before the 3rd cycle of QTx (48.5 ± 7.0 vs. 54.3 ± 2.3 mol NADPH/min/gHb). Conclusions: These data suggest that zinc supplementation reduces complaints related to the change in salivary gland, preserving the quality of life and preventing the worsening of fatigue. The increase in SOD can be attributed to zinc supplementation per se, whereas this mineral is a cofactor that endogenous antioxidant enzyme. The highest activity of SOD increases the production of H2O2, whose detoxification involves the participation of GPx, justifying its reduction. There were no changes in plasma levels of vitamin E, MDA and isoprostane during the study period. Considering the values of MDA and isoprostane, the data indicate that regardless of zinc supplementation, the lipid peroxidation of the cell membrane was unchanged during chemotherapy.

Conditions

Chemotherapy; Colorectal Cancer

Keywords

Oxidative stress; Zinc; Chemotherapy; Colorectal cancer

Outcome Measures

Primary Outcomes (1)

• oxidative stress markers

  SOD, GPx, MDA, Isoprostane, Vitamin C, Vitamin E

  18 months

Secondary Outcomes (1)

• FACIT-F

  18 months

Other Outcomes (1)

• CTCAE

  18 months

Study Arms (4)

Zinc chemotherapy

EXPERIMENTAL

Patients in colorectal chemotherapy supplemented with zinc

Dietary Supplement: Zinc

Placebo chemotherapy

PLACEBO COMPARATOR

Patients in colorectal chemotherapy with placebo

Other: Placebo

Zinc Control

OTHER

Healthy volunteers supplemented with zinc

Dietary Supplement: Zinc

Placebo Control

OTHER

Volunteers received placebo

Other: Placebo

Interventions

Zinc DIETARY_SUPPLEMENT

35 mg of elemental zinc twice daily for 16 weeks

Also known as: zinc sulfate

Zinc Control; Zinc chemotherapy

Placebo OTHER

One capsule, twice daily for 16 weeks

Also known as: Placebo capsule

Placebo Control; Placebo chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• colon or rectum adenocarcinoma stages II, III, or IV

You may not qualify if:

• liver, kidney, or chronic inflammatory autoimmune diseases;
• active infectious diseases;
• undergoing therapy with immunosuppressant;
• use vitamin or mineral supplementation;
• had been under chemo- or radiotherapy in the previous twelve months.

Sponsors & Collaborators

• University of Sao Paulo: lead
• Fundação de Amparo à Pesquisa do Estado de São Paulo: collaborator

Study Sites (1)

Division of Medical Nutrition, Department of Internal Medicine

Ribeirão Preto, São Paulo, 14049-900, Brazil

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Zinc; Zinc Sulfate

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Metals, Heavy; Elements; Inorganic Chemicals; Transition Elements; Metals; Sulfates; Sulfuric Acids; Sulfur Acids; Sulfur Compounds; Zinc Compounds

Study Officials

• Sofia Miranda Ribeiro, R.D., MSc

  University of Sao Paulo

  PRINCIPAL INVESTIGATOR

• Selma Freire Cunha, M.D., PhD

  University of Sao Paulo

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D., PhD

Study Record Dates

• First Submitted: March 31, 2014
• First Posted: April 8, 2014
• Study Start: May 1, 2011
• Primary Completion: October 1, 2011
• Study Completion: December 1, 2012
• Last Updated: April 8, 2014

Record last verified: 2014-04

Locations

BR (1)