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, A. K. Bhattacharyya, Jose Guillen, Mary Krutzsch, Ashok K. Batta, Gerald Salen, Liane Fales, Kris Koonce, Dianne Parish, Mary Clouser, Denise Roe, Peter Lance

Research output: Contribution to journalArticlepeer-review

205 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
StatePublished - Jun 1 2005

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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