Modulation of Immune Response by Oral Zinc Supplementation in Chemotherapy for Colon Cancer

Modulation of Immune Response by Oral Zinc Supplementation in Adjuvant Chemotherapy for Colon Cancer: a Study of Global Gene Expression and Function of Humoral Immunity and Neutrophils

In leukocytes of patients undergoing adjuvant chemotherapy for colon cancer treatment: a)identify genes modulated by oral supplementation of zinc; b) evaluate the effects of oral zinc supplementation on humoral immunity and neutrophil function. The study will be conducted on 30 adult patients aged grater than 18 years, of both genders who have undergone surgical resection of colonic neoplastic lesions without metastatic lesion. Patients will be randomized into two groups, with the first (Group QT Zn, n = 15) receive 70 mg/d of zinc for 16 weeks and the second will receive placebo (QT Placebo Group, n = 15). The study will also include 30 healthy volunteers who receive supplementation of 70 mg/d of Zn (C Zn group, n = 15) or placebo (Group C Placebo, n = 15). Zinc supplementation or placebo for all study groups will start two days before the volunteers received the pneumococcal vaccine, polyvalent 23. Fifteen days after vaccination, patients begin chemotherapy as pre-established criteria by the Oncology Service. Will be monitored the parameters of nutritional status (anthropometry, bioelectrical impedance, food intake, and laboratory tests) adverse effects, according to rules of the CTCAE. In the evaluation of humoral immunity, antibodies opsonization and in the pneumococcal polysaccharide will be measured. Will be evaluated the function of neutrophils by measuring DNA NETs and quantified calprotectin and elastase released in the culture supernatants of activated neutrophils. RT-qPCR will be done of genes differentially expressed(DEGS) on activated leukocytes. In six volunteers from each group will be analyzed global gene expression from RNA extracted from leukocytes by microarray; will be detected and correlated the molecular pathways modulated by zinc by MetaCore software (GeneGo). The DEGS will be validated by RT-qPCR.

Study Overview

• Status: Unknown
• Conditions: Colon Cancer; Immunity; Adjuvant Chemotherapy
• Intervention / Treatment: Dietary supplement: zinc; Other: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo
    • Ribeirao Preto, Sao Paulo, Brazil, 14049-900
      • Departament of Clinical Oncology, Sao Paulo University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age greater than 18 years
• Diagnostic histopathology of colon cancer stage III (Dukes' stage C)
• Performance Scale Karnofsky greater or equal to 70%
• Have been subjected to resection of the primary neoplastic lesion in more than 8 weeks before start of chemotherapy
• Patient in the first cycle of chemotherapy in adjuvant XELOX regimen.

Exclusion Criteria:

• Patients with a history of autoimmune or inflammatory disease, active infectious disease, liver disease, renal failure or diabetes mellitus
• Patients with metastatic disease
• Have previously received radiotherapy or chemotherapy
• Use of GCSF-Granulokine ® (growth-stimulating factor granulocyte)
• Use of immunosuppressive drugs, diuretics and supplements of zinc or copper.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Chemotherapy and zinc; Patients in adjuvant chemotherapy supplemented with zinc	Dietary supplement: zinc; zinc sulfate, 35 mg twice daily for 4 months
Placebo Comparator: Chemotherapy placebo; Patients in adjuvant chemotherapy with placebo	Other: Placebo; Placebo, One capsule, twice daily for 4 months
Other: Control and zinc; Healthy patients supplemented with zinc	Dietary supplement: zinc; zinc sulfate, 35 mg twice daily for 4 months
Other: Control Placebo; Healthy volunteers received placebo	Other: Placebo; Placebo, One capsule, twice daily for 4 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gene expression	Modulation of genes related to immune response	18 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Humoral immunity and neutrophil function	18 months

Collaborators and Investigators

• Sponsor: University of Sao Paulo
• Collaborators: Fundação de Amparo à Pesquisa do Estado de São Paulo
• Investigators: Study Director: Selma Freire C. Cunha, PhD, Sao Paulo University; Principal Investigator: Camila Bitu M. Braga, Msc, Sao Paulo University

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (Anticipated): December 1, 2011
• Study Completion (Anticipated): August 1, 2013

Study Registration Dates

• First Submitted: December 16, 2010
• First Submitted That Met QC Criteria: December 16, 2010
• First Posted (Estimate): December 17, 2010

Study Record Updates

• Last Update Posted (Estimate): December 17, 2010
• Last Update Submitted That Met QC Criteria: December 16, 2010
• Last Verified: December 1, 2010

More Information

Terms related to this study

• Keywords: Gene expression; Humoral immunity; Neutrophil function
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Colorectal Neoplasms; Colonic Neoplasms
• Other Study ID Numbers: FAPESP:2010/08787-1