Calcium and Vitamin D vs Markers of Adenomatous Polyps
Condition: Colorectal Adenomatous Polyps
MeSH terms: Adenomatous Polyps; Polyps
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to test whether calcium and/or vitamin D supplementation
      favorably affects a set of biomarkers of risk for colon cancer in persons who are at higher
      than average risk for colon cancer (ie, have already undergone the removal of adenomatous
      polyps, which are known to be precursors to developing colon cancer).
    

Detailed description: 
      There is strong biologic plausibility and animal experimental evidence for protection against
      colorectal cancer by calcium and vitamin D, calcium significantly reduced adenoma recurrence
      in a large clinical trial in humans (yet the previously reported observational evidence,
      although generally supportive, is inconsistent), and the observational literature strongly
      supports protection from vitamin D. A close physiological relationship between calcium and
      vitamin D has long been known. Yet, other than a possible reduction of colorectal epithelial
      cell proliferation by calcium, the effects of calcium and vitamin D, individually or jointly,
      on the normal human colorectal epithelium remain unknown. There have been no clinical trials
      involving vitamin D individually or jointly with calcium related to colorectal cancer
      chemoprevention in humans. There are currently no generally accepted pre-neoplastic
      biomarkers of risk for colorectal cancer other than the possible exception of proliferation
      markers that, at best, have limited usefulness as individual markers. Based on recent
      advances in understanding the molecular basis of colorectal cancer, we developed a panel of
      newer, plausible, reliable, immunohistochemically detected biomarkers that provides molecular
      phenotyping of the normal appearing colorectal epithelium: 1) inflammation (COX-2), 2) the
      expression of genes involved in the normal structure and function of the colorectal
      epithelium that have been found to be altered early in the two major colorectal
      carcinogenesis pathways (APC, MSH2, MLH1), and 3) a more complete picture of the cell cycle
      events in colorectal epithelial crypt cells (short and long-term proliferation: MIB-1 and
      telomerase; differentiation: p21; apoptosis inhibition and promotion: bcl-2, bax, and bak)
      that has not yet been tested in a chemoprevention trial.

      To address these needs, we will conduct a preliminary, randomized, double-blind,
      placebo-controlled, 2 x 2 factorial chemoprevention trial (n = 88) of calcium 2,000 mg/day
      and vitamin D3 800 IU/day, alone and in combination vs placebo over 6 months in patients with
      recent removal of sporadic adenomatous colorectal polyps, to investigate their effects on the
      individual components and aggregate profile of our colorectal cancer risk biomarker panel. We
      will also examine study results stratified by NSAID use and Bsm I vitamin D receptor
      genotypes. The preliminary estimates of treatment effect sizes and variabilities will be used
      to refine the biomarker panel and study design and to calculate the needed sample size for a
      potential full-scale study.

      We assert that using biological measurements of risk, as they have for ischemic heart
      disease, will result in a decline in colorectal cancer incidence and mortality. The proposed
      project is borne of this vision, and has intertwined missions of exploring the efficacy of
      two plausible and evidentially well-supported dietary agents, calcium and vitamin D, on the
      modulation of a plausible panel of molecular phenotypic biomarkers of risk for colorectal
      neoplasia.
    

Intervention name(s): Calcium and vitamin D3 combined; Placebo; Calcium; Vitamin D3
Intervention type(s): Dietary Supplement; Drug; Dietary Supplement; Dietary Supplement
Intervention description(s): Calcium 2,000 mg (as calcium carbonate) + vitamin D3 800 IU given in equal divided doses twice daily with food over 6 months; Placebo; Calcium 2,000 mg/day as calcium carbonate in two divided doses with meals over 6 months; Vitamin D3 800 IU given as 400 IU twice daily with food over 6 months
Intervention MeSH terms: Calcium, Dietary; Vitamin D; Ergocalciferols; Cholecalciferol; Vitamins; Calcium
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: colonic polyps; adenomatous polyps; colon cancer prevention; dietary supplements