Vitamin D/Calcium Polyp Prevention Study
Condition: Colorectal Cancer; Polyps; Adenomas
MeSH terms: Adenoma; Polyps
Study type: Interventional
Phase: Phase 2/Phase 3

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 description: 
      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. In the primary analyses, the occurrence of new adenomas in the interval
      between randomization and the follow-up exam will be compared between subjects randomized to
      vitamin D (with or without calcium) versus those randomized to no vitamin D (with or without
      calcium), between subjects randomized to calcium (with or without vitamin D) versus those
      randomized to no calcium (with or without vitamin D; excluding women electing to receive
      calcium who therefore cannot participate in the calcium component of the study), and between
      those randomized to calcium plus vitamin D versus those randomized to calcium alone. In
      secondary analyses, we will examine the impact of baseline vitamin D levels and vitamin D
      receptor (VDR) polymorphisms on the vitamin D effects. Effects on advanced adenomas will also
      be assessed as a secondary outcome. Participants will be invited to participate in an
      optional Observational Follow Up phase of the study that will begin following the end of
      treatment. In this phase of the study, subjects will continue to be followed on an
      observational basis (no study treatment) with annual questionnaires until the time of a
      subsequent colonoscopy that is at least three years from the follow up colonoscopy at which
      study treatment was ended. We will examine the occurrence of new adenomas in the interval
      between the colonoscopy exam at the end of study treatment and the exam at the end of
      observational follow up period.
    

Intervention name(s): Calcium Carbonate; Vitamin D3; placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 3 gm/daily; 1200 mg elemental calcium/daily; two tablets per day; 600 mg elemental calcium/tablet; 1000 IU/daily; two tablets per day; 500 IU per tablet; placebo; two tablets per day
Intervention MeSH terms: Vitamin D; Cholecalciferol; Calcium Carbonate; Calcium
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Colorectal neoplasms; Adenomatous polyps