Clinical Trial: Calcium and Vitamin D vs Markers of Adenomatous Polyps

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

Official Title: Calcium, Vitamin D, and Colon Cancer Risk Biomarkers

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).

Detailed Summary:

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 preli
Sponsor: Emory University

Current Primary Outcome: 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


Original Primary Outcome: Efficacy and variability of response of supplemental calcium and/or vitamin D3 vs. placebo over 6 months in patients with recent removal of adenomatous colorectal polyp on a panel of biomarkers of risk for colorectal cancer.

Current Secondary Outcome:

  • Vitamin D metabolites [ Time Frame: 6 months ]
    serum 25-OH-vitamin D3 and 1,25-OH-vitamin D3
  • Circulating inflammation markers [ Time Frame: 6 months ]
    serum CRP, TNF-α, IL-6, IL-1β, IL-8 and IL-10


Original Secondary Outcome:

  • 1.Variation in response according to nonsteroidal anti-inflammatory drug (NSAID) use or Bsm I vitamin D receptor genotype
  • 2.Normal variation of the biomarker panel relative to inter- and intra-subject components of variability over 6 months


Information By: Emory University

Dates:
Date Received: September 13, 2005
Date Started: May 2005
Date Completion:
Last Updated: November 22, 2013
Last Verified: November 2013