Phase III trial of ursodeoxycholic acid to prevent colorectal adenoma recurrence

David S Alberts, María Elena Martínez, Lisa M. Hess, Janine G Einspahr, Sylvan B. Green, Achyut K Bhattacharyya, Jose Guillen, Mary Krutzsch, Ashok K. Batta, Gerald Salen, Liane Fales, Kris Koonce, Dianne Parish, Mary Clouser, Denise Roe, Michael P Lance

Research output: Contribution to journalArticle

171 Scopus citations


Background: Ursodeoxycholic acid (UDCA) treatment is associated with a reduced incidence of colonic neoplasia in preclinical models and in patients with conditions associated with an increased risk for colon cancer. We conducted a phase III, double-blind placebo-controlled trial of UDCA to evaluate its ability to prevent colorectal adenoma recurrence. Methods: We randomly assigned 1285 individuals who had undergone removal of a colorectal adenoma within the past 6 months to daily treatment with UDCA (8-10 mg/kg of body weight; 661 participants) or with placebo (624 participants) for 3 years or until follow-up colonoscopy. Recurrence rates (number of recurrent adenomas per unit time) were compared by use of a Huber-White variance estimator. Proportions of participants with one or more recurrent adenomas were compared with a Pearson chi-square statistic; adjusted odds ratios (ORs) were obtained by logistic regression. All statistical tests were two-sided. Results: We observed a non-statistically significant 12% reduction in the adenoma recurrence rate associated with UDCA treatment, compared with placebo treatment. However, UDCA treatment was associated with a statistically significant reduction (P = .03) in the recurrence of adenomas with high-grade dysplasia (adjusted OR = 0.61, 95% confidence interval = 0.39 to 0.96). We observed no statistically significant differences between UDCA and placebo groups in recurrence with regard to adenoma size, villous histology, or location. Conclusions: UDCA treatment was associated with a non-statistically significant reduction in total colorectal adenoma recurrence but with a statistically significant 39% reduction in recurrence of adenomas with high-grade dysplasia. Because severely dysplastic lesions have a high risk of progression to invasive colorectal carcinoma, this finding indicates that future chemoprevention trials of UDCA in individuals with such lesions should be considered.

Original languageEnglish (US)
Pages (from-to)846-853
Number of pages8
JournalJournal of the National Cancer Institute
Issue number11
Publication statusPublished - Jun 1 2005


ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this