Vitamin D/Calcium Polyp Prevention Study

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier:
NCT00153816
First received: September 7, 2005
Last updated: May 28, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer
Polyps
Adenomas
Drug: Calcium Carbonate
Drug: Vitamin D3
Drug: placebo
Phase 2
Phase 3

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: Vitamin D/Calcium Polyp Prevention Study

Resource links provided by NLM:


Further study details as provided by Dartmouth-Hitchcock Medical Center:

Primary Outcome Measures:
  • Colorectal adenomas [ Time Frame: 1 to 5 years ] [ Designated as safety issue: No ]
  • Advanced colorectal adenomas [ Time Frame: 1 to 5 years ] [ Designated as safety issue: No ]
  • Colorectal cancers [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 2200
Study Start Date: July 2004
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: placebo
placebo
Drug: placebo
placebo; two tablets per day
Experimental: calcium
calcium carbonate
Drug: Calcium Carbonate
3 gm/daily; 1200 mg elemental calcium/daily; two tablets per day; 600 mg elemental calcium/tablet
Experimental: vitamin D
vitamin D3
Drug: Vitamin D3
1000 IU/daily; two tablets per day; 500 IU per tablet
Experimental: calcium plus vitamin D
calcium carbonate and vitamin D3
Drug: Calcium Carbonate
3 gm/daily; 1200 mg elemental calcium/daily; two tablets per day; 600 mg elemental calcium/tablet
Drug: Vitamin D3
1000 IU/daily; two tablets per day; 500 IU per tablet
Experimental: calcium (2 arm)
calcium carbonate
Drug: Calcium Carbonate
3 gm/daily; 1200 mg elemental calcium/daily; two tablets per day; 600 mg elemental calcium/tablet
Experimental: calcium plus vitamin D (2 arm)
calcium carbonate and vitamin D3
Drug: Calcium Carbonate
3 gm/daily; 1200 mg elemental calcium/daily; two tablets per day; 600 mg elemental calcium/tablet
Drug: Vitamin D3
1000 IU/daily; two tablets per day; 500 IU per tablet

Detailed 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 vitamin D receptor (VDR) polymorphisms on the vitamin D effects. Effects on advanced adenomas will also be assessed.

  Eligibility

Ages Eligible for Study:   45 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • One or more histologically verified neoplastic polyp (adenoma) that is at least 2 mm in size removed from the large bowel with the entire large bowel examined by colonoscopy and documented to be free of further polyps or areas suspicious for neoplasia within 120 days of study entry
  • Anticipated colonoscopic follow-up three years or five years after the qualifying colonoscopy
  • Age between 45 and 75 years at enrollment
  • (Women)Agreement to avoid pregnancy (i.e., use of standard contraception)
  • Willingness to forego calcium supplementation (including multivitamins containing calcium) or, for women only, option of taking calcium supplementation of 1200 mg/daily (contained in the study pills)
  • Willingness to forego vitamin D supplementation (including multivitamins containing vitamin D)
  • Agreement to daily dietary intake of the equivalent of not more than 1200 mg calcium
  • Agreement to daily dietary intake of the equivalent of not more than 400 IU vitamin D
  • Blood calcium level within normal range
  • Blood creatinine level not to exceed 20% above upper limit of normal
  • Serum 25-(OH)-vitamin D within lower limit of normal to 70 ng/ml
  • Ability and willingness to follow the study protocol, as indicated by provision of informed consent to participate
  • Good general health, with no severely debilitating diseases or active malignancy that might compromise the patient's ability to complete the study

Exclusion Criteria:

General exclusionary criteria:

  • Participation in another colorectal (bowel) study (intervention study) in the past 5 years
  • Current participation in any other clinical trial (intervention study)
  • Pregnancy or lactation
  • A diagnosis of narcotic or alcohol dependence in the past 5 years
  • A diagnosis of dementia (e.g. Alzheimer's) in the past 5 years
  • A diagnosis of a significant psychiatric disability (e.g. Schizophrenia, refractory bipolar disorder, current severe depression) in the past 5 years

Exclusions due to derangement of calcium metabolism or indications /contraindications to study agents:

  • Any diagnosis of kidney stones
  • A diagnosis of granulomatous diseases, e.g. sarcoidosis, active chronic fungal or mycobacterial infections (tuberculosis, histoplasmosis, coccidioidomycosis, blastomycosis), berylliosis, Wegener's granulomatosis in the past 5 years
  • A diagnosis of hyperparathyroidism or other serious disturbance of calcium metabolism in the past 5 years
  • A diagnosis of severe kidney disease, e.g. chronic renal failure in the past 5 years
  • A diagnosis of unexplained hypercalcemia in the past 5 years
  • Any Diagnosis of osteoporosis with physician recommendation for treatment of low bone mass
  • A diagnosis of two or more low trauma fractures in the past 5 years
  • A diagnosis of a medical condition requiring treatment with vitamin D (e.g. osteomalacia) in the past 5 years

Exclusions due to intestinal or bowel problems:

  • Any diagnosis of invasive carcinoma of the large bowel (even if confined to a polyp)
  • Any diagnosis of familial colorectal cancer syndromes, e.g. Familial Adenomatous Polyposis (FAP) (including Gardner syndrome, Turcot's syndrome), Hereditary Nonpolyposis Colorectal Cancer (HNPCC), Hamartomatous Polyposis syndromes (including Peutz-Jeghers or Familial Juvenile Polyposis)
  • Any diagnosis of inflammatory bowel disease, e.g. Crohn's Disease, Ulcerative Colitis
  • A diagnosis of chronic intestinal malabsorption syndromes, e.g. celiac sprue, bacterial overgrowth, chronic pancreatitis, pancreatic insufficiency in the past 5 years
  • Any large bowel resection

Exclusions due to poor health:

  • A diagnosis of malignancy, other than non-melanoma skin cancer in the past 5 years
  • A diagnosis of severe lung disease - class 3 or 4 (e.g. chronic obstructive pulmonary disease or emphysema requiring oxygen) in the past 5 years
  • A diagnosis of severe heart disease: cardiovascular disease functional class 3 or 4 in the past 5 years
  • Any diagnosis of severe liver disease, e.g. cirrhosis

Exclusions due to shipping regulations:

  • Any current/past HIV positive diagnosis
  • Active hepatitis B, defined as : Hep B surface antigen positive
  • Active hepatitis C, defined as : measurable hepatitis C RNA

Drug exclusions:

  • Use of chronic oral corticosteroid therapy in the past 5 years
  • Use of lithium in the past 5 years
  • Use of phenytoin's in the past 5 years
  • Use of quinidine in the past 5 years
  • Use of therapeutic vitamin D in the past 5 years
  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: NCT00153816

Locations
United States, California
University of Southern California
Los Angeles, California, United States, 90089
United States, Colorado
University of Colorado
Denver, Colorado, United States, 80220
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, New Hampshire
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03766
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
United States, South Carolina
University of South Carolina
Columbia, South Carolina, United States, 29203
United States, Texas
University of Texas
Houston, Texas, United States, 77030
Puerto Rico
University of Puerto Rico
San Juan, Puerto Rico
Sponsors and Collaborators
Dartmouth-Hitchcock Medical Center
Investigators
Principal Investigator: John A. Baron, MD Dartmouth-Hitchcock Medical Center
  More Information

No publications provided by Dartmouth-Hitchcock Medical Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier: NCT00153816     History of Changes
Other Study ID Numbers: 5 R01 CA098286-03, 5R01CA098286-10
Study First Received: September 7, 2005
Last Updated: May 28, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Dartmouth-Hitchcock Medical Center:
Colorectal neoplasms
Adenomatous polyps

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

ClinicalTrials.gov processed this record on July 28, 2014