This project is an extension of an on-going randomized, double-blind, placebo-controlled chemoprevention trial initiated in 1991 in a population at high risk of gastric cancer living in the Colombian Andes mountains. This trial seeks to determine the efficacy of chemoprevention on the progression of premalignant gastric lesions by antioxidant supplementation and/or anti-Helicobacter pylori treatment. Using a factorial design, 863 subjects with histopathologically-determined premalignant lesions (multifocal chronic atrophic gastritis, intestinal metaplasia, mild/moderate dysplasia) were randomly-allocated to treatment with ascorbic acid (2 g/day) or placebo, beta-carotene (30 mg/day) or placebo, and anti-Helicobacter pylori treatment (bismuth plus antibiotics) or no treatment. Study subjects have been treated for a total of 3 years (1991/92-1994/95) with an endoscopy and biopsy after 3 years. They will continue on treatment for an additional three years (1994/95-1997/98) with no interruption of treatment because drugs needed for a 3-year extension have been provided. Study subjects will undergo a final endoscopy with biopsies at the end of six years of treatment. The effects of each treatment versus its placebo will be evaluated by comparing baseline and post-treatment endpoints. The primary endpoint is global histopathology and its progression rate. Secondary endpoints include expression of sulfomucins, degree of cell replication (Ki67), frequency of expression of genetic abnormalities (p53, TPR-MET, microsatellite destabilization), indicators of DNA-damage (8-hydroxyguanine adducts) and the presence and quantity of indicators of oxidative stress (iNOS, nitrotyrosine, and apoptosis).
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