Berberine Hydrochloride for the Prevention of Colorectal Adenomas: A Double-Blind, Randomised Controlled Multicenter Clinical Trial

Background: Chemoprevention of colorectal adenoma and cancer remains its importance in public health. The rate of adenoma recurrence in the first year after polypectomy is very high in East Asian populations. We aimed to investigate the clinical potential and safety of Berberine hydrochloride for colorectal adenoma recurrence. Methods: This double-blind, randomised, placebo-controlled clinical trial was done in seven hospital centers across six provinces in China. Patients with recently diagnosed adenomas and after complete polypectomy were recruited and randomized into a BBR group (Berberine hydrochloride 0.3g, twice daily) or a placebo group. They were anticipated for at least one follow-up colonoscopy until a diagnosis of CRA/CRC or the last enrolled patient reached the 2-year follow-up. The primary efficacy endpoint was the recurrence of adenomas at any follow-up colonoscopy. The secondary outcomes were the recurrences of polypoid lesions as well as advanced adenomas or CRC. Findings: Between Nov 14, 2014 and Dec 29, 2018, 1136 patients were screened for eligibility, and 1108 underwent randomization. 553 patients were assigned to receive Berberine hydrochloride and 555 to placebo. An unadjusted RR for recurrent adenomas and all polypoid lesions were 0.77 (95% CI, 0.66 to 0.91) and 0.77 (95% CI, 0.67 to 0.89), representing a decrease of 22.72% and 22.70%, respectively. No CRC occurred during the whole trial. Interaction test showed taking BBR was effective in female with unadjusted RR for recurrent adenomas of 0.58 (95% CI, 0.41 to 0.81); P=0.07 (Alpha = 0.10). No serious adverse events were reported. Interpretation: Although the mechanism has not been fully elucidated yet, Berberine hydrochloride was effective to reduce colorectal adenoma recurrence after polypectomy. Trial Registration: This trial is registered with ClinicalTrials.gov number NCT02226185. Funding Statement: This project was supported by grants from the National Natural Science Foundation of China (81421001, 81530072, 81830081 and 8177100232), the funds from Shanghai Shenkang Center (SHDC12018121), from Shanghai Municipal Key Clinical Specialty, and from Innovative research team of high-level local universities in Shanghai. The project was also partially supported by Top-Notch project of China and Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant (20152514). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: Approval for this study was obtained from the Ethics Committee of Renji Hospital, Shanghai Jiao-Tong University School of Medicine on 13th August 2014. The protocol and informed consent forms were also approved by the institutional ethics committees at each of the participating clinical centers.