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Calcium and Vitamin D vs Markers of Adenomatous Polyps (CaDvMAP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00208793
Recruitment Status : Completed
First Posted : September 21, 2005
Last Update Posted : November 26, 2013
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Roberd Bostick, MD, MPH, Emory University

Brief 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).

Condition or disease Intervention/treatment Phase
Colorectal Adenomatous Polyps Dietary Supplement: Calcium and vitamin D3 combined Drug: Placebo Dietary Supplement: Calcium Dietary Supplement: Vitamin D3 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 92 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Calcium, Vitamin D, and Colon Cancer Risk Biomarkers
Study Start Date : May 2005
Actual Primary Completion Date : September 2006
Actual Study Completion Date : February 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Calcium Vitamin D

Arm Intervention/treatment
Experimental: Calcium
Calcium 2,000 mg/day as calcium carbonate in two divided doses with food
Dietary Supplement: Calcium
Calcium 2,000 mg/day as calcium carbonate in two divided doses with meals over 6 months

Experimental: Vitamin D3
Vitamin D3 800 IU given as 400 IU twice daily with food over 6 months
Dietary Supplement: Vitamin D3
Vitamin D3 800 IU given as 400 IU twice daily with food over 6 months

Experimental: Calcium and vitamin D3 combined
Calcium 2,000 mg (as calcium carbonate) + vitamin D3 800 IU given in equal divided doses twice daily with meals over 6 months
Dietary Supplement: Calcium and vitamin D3 combined
Calcium 2,000 mg (as calcium carbonate) + vitamin D3 800 IU given in equal divided doses twice daily with food over 6 months

Placebo Comparator: Placebo Drug: Placebo

Primary Outcome Measures :
  1. Biomarkers of Risk for Colorectal Neoplasms [ Time Frame: 6 months ]
    A panel of putative biomarkers of risk for colorectal neoplasms in biopsies of normal appearing rectal mucosa: COX-2, APC, MSH-2, MLH1, MIB-1, telomerase, p21, bcl-2, bax, bak, β-catenin, E-cadherin, TGFα, TGFβ1, calcium sensing receptor, vitamin D receptor, CYP27B1, CYP24, 8-OH-dG

Secondary Outcome Measures :
  1. Vitamin D metabolites [ Time Frame: 6 months ]
    serum 25-OH-vitamin D3 and 1,25-OH-vitamin D3

  2. Circulating inflammation markers [ Time Frame: 6 months ]
    serum CRP, TNF-α, IL-6, IL-1β, IL-8 and IL-10

Information from the National Library of Medicine

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Ages Eligible for Study:   30 Years to 74 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • age 30-74
  • adenomatous colon polyp within past 3 years
  • general good health with life expectancy of at least 2 years
  • available for 8 months and able to come for clinic visits

Exclusion Criteria:

  • cancer within 5 years
  • active major disease
  • renal impairment
  • history of kidney stones
  • significant dietary change or weight loss within past 6 months
  • unable to forego usual calcium or vitamin D use during study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00208793

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United States, Georgia
The Emory Clinic, Division of Digestive Diseases
Atlanta, Georgia, United States, 30322
Sponsors and Collaborators
Emory University
National Institutes of Health (NIH)
National Cancer Institute (NCI)
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Principal Investigator: Roberd M Bostick, MD, MPH Emory University, Rollins School of Public Health & Winship Cancer Institute
Publications of Results:

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Roberd Bostick, MD, MPH, Professor, Emory University Identifier: NCT00208793    
Other Study ID Numbers: 0126-2004
R01CA104637 ( U.S. NIH Grant/Contract )
First Posted: September 21, 2005    Key Record Dates
Last Update Posted: November 26, 2013
Last Verified: November 2013
Keywords provided by Roberd Bostick, MD, MPH, Emory University:
colonic polyps
adenomatous polyps
colon cancer prevention
dietary supplements
Additional relevant MeSH terms:
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Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Vitamin D
Adenomatous Polyps
Pathological Conditions, Anatomical
Calcium, Dietary
Growth Substances
Physiological Effects of Drugs
Calcium-Regulating Hormones and Agents
Bone Density Conservation Agents