Calcium and Vitamin D vs Markers of Adenomatous Polyps (CaDvMAP)
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| ClinicalTrials.gov Identifier: NCT00208793 |
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Recruitment Status :
Completed
First Posted : September 21, 2005
Last Update Posted : November 26, 2013
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| 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 |
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.
| 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 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Calcium
Calcium 2,000 mg/day as calcium carbonate in two divided doses with food
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Dietary Supplement: Calcium
Calcium 2,000 mg/day as calcium carbonate in two divided doses with meals over 6 months |
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Experimental: Vitamin D3
Vitamin D3 800 IU given as 400 IU twice daily with food over 6 months
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Dietary Supplement: Vitamin D3
Vitamin D3 800 IU given as 400 IU twice daily with food over 6 months |
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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
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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 |
- 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
- 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
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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
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 ClinicalTrials.gov identifier (NCT number): NCT00208793
| United States, Georgia | |
| The Emory Clinic, Division of Digestive Diseases | |
| Atlanta, Georgia, United States, 30322 | |
| Principal Investigator: | Roberd M Bostick, MD, MPH | Emory University, Rollins School of Public Health & Winship Cancer Institute |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Roberd Bostick, MD, MPH, Professor, Emory University |
| ClinicalTrials.gov 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 |
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colonic polyps adenomatous polyps colon cancer prevention dietary supplements |
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Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Vitamin D Vitamins Adenomatous Polyps Polyps Pathological Conditions, Anatomical Adenoma Calcium, Dietary |
Ergocalciferols Cholecalciferol Calcium Micronutrients Nutrients Growth Substances Physiological Effects of Drugs Calcium-Regulating Hormones and Agents Bone Density Conservation Agents |