Clinical trial NCT01261962: Modulation of Immune Response by Oral Zinc Supplementation in Chemotherapy for Colon Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Adjuvant Chemotherapy
Colon Cancer
Immunity
Keywords: Humoral immunity
Neutrophil function
Gene expression
Lead sponsor: University of Sao Paulo
Sponsor class: OTHER
Collaborators: name: Fundação de Amparo à Pesquisa do Estado de São Paulo
First posted: 2010-12-17
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Gene expression
timeFrame: 18 months
Secondary outcomes:
measure: Humoral immunity and neutrophil function
timeFrame: 18 months
Other outcomes:
Locations:
city: Ribeirao Preto
country: Brazil
facility: Departament of Clinical Oncology, Sao Paulo University
state: Sao Paulo
Study officials:
affiliation: Sao Paulo University
name: Selma Freire C. Cunha, PhD
role: STUDY_DIRECTOR
affiliation: Sao Paulo University
name: Camila Bitu M. Braga, Msc
role: PRINCIPAL_INVESTIGATOR
References: