Curcumin Suppresses Growth of Recurrent Colorectal Adenoma After Endoscopic Resection: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial.

Abstract

Experimental and limited clinical studies suggest that curcumin has chemopreventive activity in the colorectum. This large-scale clinical trial evaluated the efficacy and safety of curcumin in patients with previously endoscopically resected colorectal neoplasia. This randomized, double-blind, placebo-controlled multicenter trial enrolled patients with previously resected colorectal neoplasia. Eligible patients were randomly assigned (1:1), using a stratified, computer-generated scheme to receive oral submicron-powdered curcumin (Theracurmin®; 180 mg twice daily) or identical placebo capsules for 2 years. All analyses were performed according to a modified intention-to-treat principle including all randomly assigned patients who underwent the 2-year colonoscopy. Between April 1, 2016, and March 31, 2020, 577 patients were randomly assigned to curcumin (n=287) or placebo groups (n=290). The detection rate of recurrent colorectal adenomas at 2 years, the primary endpoint, did not differ significantly between groups (risk ratio [RR] 0.98; 95% CI 0.82-1.16). However, the detection rate of adenomas ≥6 mm, a prespecified lesion category recommended for endoscopic resection in Japanese guidelines, was significantly lower with curcumin (RR, 0.56; 95% CI, 0.33-0.95; P=0.04). The per-patient number of adenomas ≥6 mm was also significantly lower (P=0.03), and the median size of all detected adenomas was significantly smaller in the curcumin group (P=0.003). The inhibitory effect appeared more pronounced in patients with higher baseline adenoma burden and in men in exploratory analyses. Treatment-related adverse events were infrequent and mild. Curcumin inhibited the growth of recurrent colorectal adenomas, despite no significant reduction in the overall incidence of recurrence. This is the first large-scale randomized clinical trial demonstrating the suppressive efficacy of curcumin against colorectal neoplasia, and also highlighting the importance of incorporating growth-related endpoints, in addition to incidence- or detection-based endpoints, in chemoprevention studies. (jRCTs061180079).