This randomized phase IIb trial studies how well curcumin works in preventing gastric cancer in patients with chronic atrophic gastritis and/or gastric intestinal metaplasia. Curcumin is an antioxidant compound found in plants that may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES: I. To compare the change in gastric mucosal interleukin 1beta (IL-1beta) cytokine level, quantified by Luminex assay technology, after a 6-month intervention in participants randomly assigned to the curcumin (Meriva \[curcuminoids\]) versus placebo arms. SECONDARY OBJECTIVES: I. To determine the safety and tolerability of Meriva versus placebo. II. To compare changes in Histology Gastric Score (HGS) from baseline to 6 months for Meriva versus placebo. III. To compare changes in additional gastric mucosal cytokine/chemokine levels (interleukin 8 \[IL-8\], tumor necrosis factor-alpha \[TNFalpha\], and inducible protein 10 \[IP-10\]; quantified by Luminex assay). IV. To compare changes in gastric mucosal deoxyribonucleic acid (DNA) damage as assessed by immunohistochemistry (IHC), of the biomarkers 8-hydroxy-2'-deoxyguanosine (8-OHdG) and phosphorylated subtype of histone H2A (H2AX). V. To explore associations between proinflammatory cytokine genotype status (IL-1beta, IL-8, and TNFalpha single nucleotide polymorphisms \[SNPs\]; characterized at baseline) and the above outcomes. OUTLINE: Patients are randomized into 1 of 2 arms. ARM 1: Patients receive curcumin orally (PO) twice daily (BID) for 180 days in the absence of unacceptable toxicity. ARM 2: Patients receive placebo PO BID for 180 days in the absence of unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and 7 months.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
50
Hospital Regional de Occidente
Santa Rosa de Copán, Honduras
University of Puerto Rico
San Juan, Puerto Rico
Absolute Change in IL-1beta Cytokine Levels in the Gastric Mucosa
Will be measured by Luminex assay. If the data are not normally distributed, the Wilcoxon Rank-Sum test will be used. The 95% confidence intervals will also be provided.
Time frame: Baseline up to 6 months
Change in Histology Gastric Score
Will compare changes in histology gastric score for curcumin versus placebo. Correa Histopathology Scoring System values according to the histological diagnosis categories Histological diagnosis Correa Histopathology Scores (range) 1. Normal 1 2. non-atrophic gastritis(NAG) 2 3. multifocal atrophic gastritis without intestinal metaplasia (MAG) 3.25-4.00\* 4. IM (intestinal metaplasia) 4.30-5.00\* 5. Dysplasia 5.25-5.75\* 6. Gastric Cancer 6
Time frame: Baseline up to 6 months
Additional Gastric Mucosal Cytokine/Chemokine Levels (TNFalpha, and IP-10)
Will be quantified with Luminex assay. Changes in the concentrations (or categories) will be explored within and between the intervention arms. Fisher's exact tests, Wilcoxon rank sum tests, and two-sample t-tests will be used to assess differences between groups. McNemar's tests, Wilcoxon signed rank tests, and paired sample t-tests will be used to assess differences within each arm. Graphical methods (i.e. boxplots, scatter plots, etc.) will also be used to describe the data.
Time frame: Baseline up to 6 months
Gastric Mucosal Deoxyribonucleic Acid (DNA) Damage
Will be assessed by immunohistochemistry. Fisher's exact tests, Wilcoxon rank sum tests, and two-sample t-tests will be used to assess differences between groups. McNemar's tests, Wilcoxon signed rank tests, and paired sample t-tests will be used to assess differences within each arm. Graphical methods (i.e. boxplots, scatter plots, etc.) will also be used to describe the data.
Time frame: Baseline up to 6 months
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Ancillary studies