Vitamin D/Calcium Polyp Prevention Study
Summary
Extensive experimental and observational data suggest that intake of calcium and of vitamin D exert protective effects on colorectal neoplasia. Building on their previous work, the investigators will investigate the chemopreventive effect of vitamin D in the large bowel, to study whether calcium with vitamin D is more effective than calcium alone, and to confirm their positive finding regarding calcium. The goal of this study is the development of chemopreventive combinations that will reduce risk of colorectal neoplasia sufficiently to permit the lengthening of surveillance intervals in most patients and to clarify important issues regarding the mechanisms of colorectal carcinogenesis and chemoprevention.
Description
This study is a double-blind, placebo-controlled trial of vitamin D and/or calcium supplementation for the prevention of large bowel adenomas. Subjects will be recruited from 10 Study Centers in North America. Eligible subjects will have had at least one large bowel adenoma removed in the 4 months prior to study entry and no remaining polyps in the bowel after complete colonoscopic examination. Participants will be randomized in a modified 2 x 2 factorial design to vitamin D (1000 IU/day), calcium carbonate (1200 mg elemental calcium/day), both agents, or placebo only. Women who decline to forego calcium supplementation will be randomized only to calcium alone or to calcium plus vitamin D. Randomization will be stratified by gender, study center of recruitment, and anticipated follow-up interval (see below), and will be conducted separately for female subjects randomized only to vitamin D. We anticipate enrolling about 2500 participants to reach a total of approximately 2000 randomized subjects. As safety measures, blood levels of calcium, creatinine, and 25-(OH)-vitamin D will be obtained at baseline and 1 year after randomization, as well as 3 years after randomization for subjects with a 5-year surveillance cycle. Every six months after randomization subjects will complete a questionnaire regarding compliance with study agents, use of medications and vitamin/mineral supplements, illnesses, hospitalizations, and dietary intake of calcium and vitamin D. The endpoint of the study will be new adenomas detected on follow-up colonoscopy. These examinations are scheduled to occur either 3 years or 5 years after the qualifying examination, depending on the follow-up interval recommended by each patient's endoscopist. Some patients may, for medical reasons, have a colonoscopy at a time other than 3 or 5 years after the qualifying examination. Information from these exams will be included in analyses where appropriate. In the primary analyses, the occurrence of new neoplastic polyps in the interval between randomization and the follow-up exam will be compared between subjects randomized to vitamin D (with or without calcium) versus those randomized to placebo (with or without calcium), between subjects randomized to calcium (with or without vitamin D) versus those randomized to placebo (with or without vitamin D, excluding women electing to receive calcium and therefore cannot participate in the calcium component of the study), and between those randomized to calcium plus vitamin D versus those randomized to calcium alone. In secondary analyses, we will examine the effect of calcium plus vitamin D versus vitamin D alone, and the impact of baseline vitamin D levels and VDR polymorphisms on the vitamin D effects. Effects on advanced adenomas will also be assessed.
Study Design
Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention
Conditions
Colorectal Cancer
Intervention
Calcium Carbonate, Vitamin D3, placebo
Location
University of Southern California
Los Angeles
California
United States
90089
Status
Active, not recruiting
Source
Dartmouth-Hitchcock Medical Center
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00153816
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Colorectal Neoplasms
Tumors or cancer of the COLON or the RECTUM or both. Risk factors for colorectal cancer include chronic ULCERATIVE COLITIS; FAMILIAL POLYPOSIS COLI; exposure to ASBESTOS; and irradiation of the CERVIX UTERI.
Genes, Mcc
Tumor suppressor genes located in the 5q21 region on the long arm of human chromosome 5. The mutation of these genes is associated with the formation of colorectal cancer (MCC stands for mutated in colorectal cancer).
Genes, Dcc
Tumor suppressor genes located in the 18q21-qter region of human chromosome 18. The absence of these genes is associated with the formation of colorectal cancer (DCC stands for deleted in colorectal cancer). The products of these genes show significant homology to neural cell adhesion molecules and other related cell surface glycoproteins.
Calcium Carbonate
Carbonic acid calcium salt (CaCO3). An odorless, tasteless powder or crystal that occurs in nature. It is used therapeutically as a phosphate buffer in hemodialysis patients and as a calcium supplement.
Colorectal Neoplasms, Hereditary Nonpolyposis
A group of autosomal-dominant inherited diseases in which COLON CANCER arises in discrete adenomas. Unlike FAMILIAL POLYPOSIS COLI with hundreds of polyps, hereditary nonpolyposis colorectal neoplasms occur much later, in the fourth and fifth decades. HNPCC has been associated with germline mutations in mismatch repair (MMR) genes. It has been subdivided into Lynch syndrome I or site-specific colonic cancer, and LYNCH SYNDROME II which includes extracolonic cancer.
Clinical Trials
Vitamin D, Insulin Resistance, and Cardiovascular Disease
In recent years, vitamin D has been shown not only to be important for bone and calcium metabolism but also for homeostasis of critical tissues involved in vascular disease in patients wit...
RATIONALE: The use of cholecalciferol and calcium carbonate may keep colon cancer from coming back in patients with colon cancer that has been removed by surgery. PURPOSE: This randomized...
Regulation of Bone Formation in Renal Osteodystrophy
To examine the effects of two types of active vitamin D (calcitriol and doxercalciferol) and two phosphate binders (sevelamer and calcium carbonate) on the bone disease and blood tests of...
Effect of Vitamin D and Calcium on Genes in the Colon
The researchers are involved in a research program to understand how vitamin D and calcium in the diet or as supplements may lower the risk of colorectal polyps and cancer. To that end, th...
RATIONALE: Zoledronate, vitamin D and calcium may prevent or delay bone pain and other symptoms caused by bone metastases. It is not yet known whether giving zoledronate together with vita...
PubMed Articles
Vitamin D and its analogs are potent inhibitors of colorectal cancer growth and metastasis. A number of recent studies have defined the intersections between the β-catenin-TCF pathway (a known contri...
To determine whether calcium plus vitamin D supplementation (CaD) affects incidence of rheumatoid arthritis (RA). Participants enrolled in the Women's Health Initiative CaD trial (n = 36,282) were r...
Review: Vitamin D with calcium reduces fractures in adults.
QUESTION What are the benefits and harms of vitamin D supplementation, with or without calcium, in adults? REVIEW SCOPE Included studies compared oral vitamin D, with or without calcium, with placebo...
Effect of combined folic Acid, vitamin b6, and vitamin B12 on colorectal adenoma.
Background Folic acid, vitamin B(6), and vitamin B(12) act in concert in the one-carbon metabolism and may protect against colorectal neoplasia. We examined the effect of combined B-vitamin treatment...
ABSTRACT: BACKGROUND: It is undetermined whether calcium supplementation has an effect on obesity or body composition in postmenopausal women. The purpose of the study is to detect the effect of calci...
