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

This study has been completed.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Roberd Bostick, MD, MPH, Emory University
ClinicalTrials.gov Identifier:
NCT00208793
First received: September 13, 2005
Last updated: November 22, 2013
Last verified: November 2013
  Purpose

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 Intervention Phase
Colorectal Adenomatous Polyps
Dietary Supplement: Calcium and vitamin D3 combined
Drug: Placebo
Dietary Supplement: Calcium
Dietary Supplement: Vitamin D3
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Calcium, Vitamin D, and Colon Cancer Risk Biomarkers

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • Biomarkers of Risk for Colorectal Neoplasms [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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:
  • Vitamin D metabolites [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    serum 25-OH-vitamin D3 and 1,25-OH-vitamin D3

  • Circulating inflammation markers [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    serum CRP, TNF-α, IL-6, IL-1β, IL-8 and IL-10


Enrollment: 92
Study Start Date: May 2005
Study Completion Date: February 2013
Primary Completion Date: September 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Placebo

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.

  Eligibility

Ages Eligible for Study:   30 Years to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00208793

Locations
United States, Georgia
The Emory Clinic, Division of Digestive Diseases
Atlanta, Georgia, United States, 30322
Sponsors and Collaborators
Emory University
Investigators
Principal Investigator: Roberd M Bostick, MD, MPH Emory University, Rollins School of Public Health & Winship Cancer Institute
  More Information

Publications:

Responsible Party: Roberd Bostick, MD, MPH, Professor, Emory University
ClinicalTrials.gov Identifier: NCT00208793     History of Changes
Other Study ID Numbers: 0126-2004, R01CA104637
Study First Received: September 13, 2005
Last Updated: November 22, 2013
Health Authority: United States: Federal Government

Keywords provided by Emory University:
colonic polyps
adenomatous polyps
colon cancer prevention
dietary supplements

Additional relevant MeSH terms:
Polyps
Adenomatous Polyps
Pathological Conditions, Anatomical
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Vitamins
Vitamin D
Ergocalciferols
Cholecalciferol
Calcium, Dietary
Calcium Carbonate
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents
Antacids
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 30, 2014