Randomized, Double-blind, Placebo-controlled Trial of Meriva® (curcuminoids) as a Candidate Chemoprevention Agent for Gastric Carcinogenesis

Globally, gastric adenocarcinoma (GC) is the fourth leading cause of cancer mortality and a major cancer disparity in the U.S. Chemoprevention strategies are lacking for high-risk individuals with gastric premalignant conditions (GPMC). Curcumin, the principal curcuminoid in turmeric, exerts immunomodulatory effects in the epithelium and against H. pylori, and studies suggest chemoprevention potential. We conducted a double-blind, phase IIa randomized controlled trial in high-risk populations in Puerto Rico and Honduras. We investigated the utility of a bioavailable formulation of curcumin (Meriva®) among individuals with H. pylori-negative GPMC, specifically, multifocal atrophic gastritis or gastric intestinal metaplasia. Patients were 1:1 randomized to 1000 mg Meriva® daily or placebo for a 6-month intervention with endoscopy at baseline and 6 months. Outcomes included assessment of epithelial cytokine and chemokine levels, histology, and DNA damage as assessed by the pH2AX IHC. Of the 110 subjects screened, 50 participants were randomized and 48 completed the trial. A significant reduction in gastric mucosal IL-1β levels from baseline in the gastric body, the primary endpoint, was observed in the Meriva® group (p=0.032). Changes in epithelial IL-8, TNFα, and IP-10 levels, and gastric mucosal histology and DNA damage (secondary endpoints) were similar between arms. Curcumin (Meriva®) was safe, well tolerated, and showed potential as a curcuminoid chemoprevention agent in H. pylori-negative GPMC patients. A potential reduction in gastric inflammation as measured by gastric mucosal IL-1β levels was observed. Further studies are warranted, including studies in H. pylori-positive individuals, based upon the curcuminoid direct effects on H. pylori.