A Phase I Trial of Berberine in Chinese with Ulcerative Colitis.

Abstract

The Chinese natural product, berberine, has biological properties that support its potential efficacy as a colon cancer prevention agent. Its longstanding use in China to treat gastrointestinal tract and rheumatologic disorders is generally regarded as safe, supporting initial investigations in an at-risk population, such as individuals with ulcerative colitis. However, the safety of berberine in this population is not established. Individuals living in China with biopsy-proven ulcerative colitis, ≤grade 2 dysplasia, and with a ulcerative colitis disease activity index (UCDAI) score ≤1 on mesalamine, were randomized 3:1 in a double-blind phase I trial to berberine 900 mg/day or placebo for 3 months, with the primary objective of assessing safety. Blood samples and biopsies of the colorectum, from prespecified locations, were collected prior to and following therapy. Secondary endpoints included changes in UCDAI score, and in tissue and plasma markers of inflammation. Of toxicities at least possibly related, one episode of grade 3 elevation in transaminases and one episode of grade 1 nausea were observed among 12 individuals on berberine, and none were observed among 4 on placebo. The mean plasma berberine concentration was 3.5 nmol/L after berberine treatment, significantly higher than 0.5 nmol/L with placebo. Berberine significantly decreased the Geboes grade in colonic tissue, but had a nonsignificant effect on other tissue or blood biomarkers related to cell growth and inflammation. The combination of berberine and mesalamine is well tolerated in Chinese with ulcerative colitis and may enhance mesalamine's anti-inflammatory effects in colonic tissue.

• Authors: Li Xu, Yujie Zhang, Xianmin Xue, Jie Liu, Zeng-Shan Li, Guang-Yu Yang, Ying Song, Yan Pan, Yueyun Ma, Sijun Hu, Aidong Wen, Yanyan Jia, Luz Maria Rodriguez, Mary Beth Tull, Kelly Benante, Seema A Khan, Ying Cao, Borko Jovanovic, Ellen Richmond, Asad Umar, Raymond Bergan, Kaichun Wu
• Journal: Cancer prevention research (Philadelphia, Pa.) (Cancer Prev Res (Phila)) Vol. 13 Issue 1 Pg. 117-126 (01 2020) ISSN: 1940-6215 [Electronic] United States
• PMID: 31619442 (Publication Type: Clinical Trial, Phase I, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: ©2019 American Association for Cancer Research.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Berberine
• Mesalamine

Topics

• Administration, Oral
• Adult
• Anti-Inflammatory Agents, Non-Steroidal (administration & dosage, adverse effects, pharmacokinetics)
• Berberine (administration & dosage, adverse effects, pharmacokinetics)
• Biopsy
• China
• Colitis, Ulcerative (diagnosis, drug therapy, immunology, pathology)
• Colon (drug effects, immunology, pathology)
• Colorectal Neoplasms (immunology, pathology, prevention & control)
• Double-Blind Method
• Drug Synergism
• Drug Therapy, Combination
• Female
• Humans
• Intestinal Mucosa (drug effects, immunology, pathology)
• Male
• Mesalamine (administration & dosage, adverse effects, pharmacokinetics)
• Middle Aged
• Prospective Studies
• Rectum (drug effects, immunology, pathology)
• Severity of Illness Index
• Tissue Distribution
• Young Adult