Clinical Trial: Vitamin D/Calcium Polyp Prevention Study

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Vitamin D/Calcium Polyp Prevention Study

Brief Summary: Extensive experimental and observational data suggest that intake of calcium and of vitamin D exert protective effects on colorectal neoplasia. Building on their previous work, the investigators will investigate the chemopreventive effect of vitamin D in the large bowel, to study whether calcium with vitamin D is more effective than calcium alone, and to confirm their positive finding regarding calcium. The goal of this study is the development of chemopreventive combinations that will reduce risk of colorectal neoplasia sufficiently to permit the lengthening of surveillance intervals in most patients and to clarify important issues regarding the mechanisms of colorectal carcinogenesis and chemoprevention.

Detailed Summary: This study is a double-blind, placebo-controlled trial of vitamin D and/or calcium supplementation for the prevention of large bowel adenomas. Subjects will be recruited from 11 Study Centers in North America. Eligible subjects will have had at least one large bowel adenoma removed in the 4 months prior to study entry and no remaining polyps in the bowel after complete colonoscopic examination. Participants will be randomized in a partial 2 x 2 factorial design to vitamin D (1000 IU/day), calcium carbonate (1200 mg elemental calcium/day), both agents, or placebo only (Full Factorial randomization). Women who decline to forego calcium supplementation will be randomized only to calcium alone or to calcium plus vitamin D (Two Arm randomization). Randomization will be stratified by gender, study center of recruitment, and anticipated follow-up interval (see below), and will be conducted separately for female subjects randomized only to vitamin D. We anticipate enrolling up to 3000 participants to reach a total of up to 2400 randomized subjects. As safety measures, blood levels of calcium, creatinine, and 25-(OH)-vitamin D will be obtained at baseline and 1 year after randomization, as well as 3 years after randomization for subjects with a 5-year surveillance cycle. Every six months after randomization subjects will complete a questionnaire regarding compliance with study agents, use of medications and vitamin/mineral supplements, illnesses, hospitalizations, and dietary intake of calcium and vitamin D. The primary endpoint of the study will be new adenomas detected on follow-up colonoscopy. These examinations are scheduled to occur either 3 years or 5 years after the qualifying examination, depending on the follow-up interval recommended by each patient's endoscopist. Some patients may, for medical reasons, have a colonoscopy at a time other than 3 or 5 years after the qualifying examination. Information from these exams will be included in analyses where appropriate.
Sponsor: Dartmouth-Hitchcock Medical Center

Current Primary Outcome: Colorectal Adenomas [ Time Frame: 1 to 10 years ]

Original Primary Outcome:

  • 1. Supplementation with vitamin D3 (1000 IU/day) reduces the risk of new adenomas in patients with a recent history of these tumors.
  • 2. Supplementation with calcium carbonate (1200 mg elemental calcium/day) reduces the risk of new adenomas
  • 3. Supplementation with both vitamin D3 (1000 IU/day) and calcium carbonate (1200 mg elemental calcium/day) reduces the risk of new adenomas more than supplementation with calcium carbonate alone.


Current Secondary Outcome: Advanced Colorectal Lesions [ Time Frame: 1 to 10 years ]

Includes: adenomas >=1 cm, adenomas with high grade dysplasia, adenomas with villous features, or cancer.


Original Secondary Outcome:

  • 1. Supplementation with both vitamin D3 and calcium carbonate reduces the risk of new adenomas more than supplementation with vitamin D3 alone.
  • 2.Supplementation with vitamin D3 will have a greater effect among individuals whose initial serum 25-OH vitamin D level is less than the overall median, compared with subjects whose levels are greater than the median.
  • 3.The effects of calcium and vitamin D on adenoma occurrence will be more marked for adenomas with advanced histology (>25% villous features, advanced dysplasia) than for tubular adenomas.
  • 4. The effect of supplementation with vitamin D3 will be modified by polymorphisms at the 3' end of the vitamin D receptor gene.


Information By: Dartmouth-Hitchcock Medical Center

Dates:
Date Received: September 7, 2005
Date Started: July 2004
Date Completion:
Last Updated: February 6, 2017
Last Verified: February 2017