Abstract CT335: A clinical trial of supplementation with vitamin D and/or calcium for the prevention of colorectal adenomas
Authors: Baron John A. , Barry Elizabeth L. , Ahnen Dennis J. , Burke Carol A. , Bostick Roberd M. , Bresalier Robert S. , Church Timothy R. , Cruz-Correa Marcia , Goodman Michael , Haile Robert , Ivanova Anastasia , Rothstein Richard I. , Sandler Robert S. , Snover Dale , Summers Robert W. 
Published: May 2015

Abstract
Considerable epidemiological and preclinical evidence suggests that high vitamin D status confers a lower risk of colorectal neoplasia. High calcium intake has also been associated with reduced risks, and trials using calcium have shown a reduction in the occurrence of adenomas. To study these issues, we conducted a randomized, double blind, placebo-controlled trial of supplementation with vitamin D and/or calcium for the prevention of colorectal adenomas. We hypothesized that subjects receiving Vitamin D supplementation would have a lower risk of metachronous adenomas than those given placebo, that those randomized to calcium would have a lower risk, and that subjects given calcium and vitamin D together would have a lower risk than those given calcium alone. Secondary hypotheses involved effects of study agents on advanced lesions.
Methods: In 11 US centers, we recruited subjects recently diagnosed with at least one adenoma; with no known polyps remaining in the bowel; and with no known contraindication to, or need for, the study agents. In a modified 2 x 2 factorial design, 2259 subjects were randomized to vitamin D3 (1000 IU daily), calcium (1200 mg daily), both agents, or neither. Women could elect to be randomized only to vitamin D. Follow-up colonoscopy was planned by the subjects’ clinicians at either 3 or 5 years after the baseline exam. Every 6 months, subjects were queried about endoscopic procedures, major medical events, and compliance with study procedures. Intention to treat risk ratios (RRs) and 95% confidence intervals (CIs) were computed with adjustment for age, sex, study center, number of baseline adenomas, planned follow-up interval (3 or 5 years) and participation in calcium randomization.
Results: Treatment arms were well balanced with regard to personal characteristics and risk factors for metachronous neoplasia. Treatment adherence was very good; 90% of subjects reported taking at least half their study tablets during the trial. About 93% of subjects had a follow-up colonoscopy at least 1 year after randomization; nearly all were complete examinations. Baseline 25-OH vitamin D levels were 24.6 ng/ml overall; by the end of study treatment, subjects given vitamin D had levels 7.8 ng/ml higher than those given placebo. Overall, 42% of subjects had one or more adenomas during follow-up (mean size 5 mm).
The study treatments had no effect on adenoma outcomes. The RR for vitamin D vs. placebo was 0.97 (95% CI 0.88-1.08); for vitamin D plus calcium vs. calcium alone, 0.99 (95% CI 0.86-1.13); and for calcium alone, 0.95 (95% CI 0.85-1.06). RRs for advanced adenomas were similar. Numbers of subjects with major medical events were low, but study agents had no material effect on risk of cardiovascular endpoints, cancer or kidney stones.
Conclusion: Despite previous evidence, we found supplemental vitamin D and calcium to be ineffective in reducing risk of metachronous colorectal adenomas over 3 - 5 years.
Citation Format: John A. Baron, Elizabeth L. Barry, Dennis J. Ahnen, Carol A. Burke, Roberd M. Bostick, Robert S. Bresalier, Timothy R. Church, Marcia Cruz-Correa, Michael Goodman, Robert Haile, Anastasia Ivanova, Richard I. Rothstein, Robert S. Sandler, Dale Snover, Robert W. Summers. A clinical trial of supplementation with vitamin D and/or calcium for the prevention of colorectal adenomas. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT335. doi:10.1158/1538-7445.AM2014-CT335