This application is for the renewal of CA098286, a multicentered, double-blind, randomized, placebo controlled trial of supplementation with vitamin D and/or calcium for the prevention of colorectal adenomas. The study builds on extensive epidemiological and experimental data indicating that both vitamin D and calcium exert anti-neoplastic effects in the large bowel. The study involves 11 clinical centers in the US, a pathology center and a coordinating center. Each subject has at least one large bowel adenoma removed in the 4 months prior to study entry, with complete colonoscopic visualization of the colorectal mucosa and no known polyps remaining in the bowel. Subjects at risk for toxicity from study agents (e.g. with a recent history of kidney stones) are excluded, as are those with a likely need for the study treatments (e.g. with osteoporosis). Participants agree to avoid taking study agents outside the trial. Suitable subjects are randomized in a 2 x 2 factorial manner to calcium carbonate (1200 mg calcium/day), vitamin D (1000 IU/day), both agents, or placebo. We offer women the choice of being randomized to calcium alone or calcium plus vitamin D. Colonoscopic follow-up occurs at either 3 years or 5 years after the qualifying exam, as planned by each subject's gastroenterologist. As safety measures, serum calcium, creatinine and 25-(OH) vitamin D levels will be obtained at baseline, and during the treatment period. The main endpoint of the study is one or more neoplastic polyps of the bowel on followup;assessment of effects for advanced lesions will be included in secondary analyses. Under conservative assumptions regarding event rates and study conduct, we will have greater than 89% power to detect a 20% reduction in adenoma recurrence with vitamin D versus placebo, and 85% power to detect a 25% reduction in recurrence with calcium plus vitamin D versus calcium alone. Other analyses will also have good statistical power. During the first 5 years of funding, enrollment has proceeded almost exactly according to schedule;we will meet or exceed our target enrollment on November 30, 2007. To date, subjects have shown excellent compliance with study procedures and agents, and few subjects have had to stop randomized treatment because of adverse events (e.g. kidney stones) or a need for the study agents (e.g. osteoporosis). We now request funds to complete the planned treatment and follow-up for all 2,200 randomized subjects, prepare for the first efficacy analyses, and implement a post-treatment follow-up.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA098286-09
Application #
8144874
Study Section
Special Emphasis Panel (ZCA1-RPRB-7 (M1))
Program Officer
Malone, Winfred F
Project Start
2002-12-01
Project End
2013-07-31
Budget Start
2011-08-01
Budget End
2012-07-31
Support Year
9
Fiscal Year
2011
Total Cost
$3,480,268
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Barry, Elizabeth L; Peacock, Janet L; Rees, Judy R et al. (2017) Vitamin D Receptor Genotype, Vitamin D3 Supplementation, and Risk of Colorectal Adenomas: A Randomized Clinical Trial. JAMA Oncol 3:628-635
Anderson, Joseph C; Baron, John A; Ahnen, Dennis J et al. (2017) Factors Associated With Shorter Colonoscopy Surveillance Intervals for Patients With Low-Risk Colorectal Adenomas and Effects on Outcome. Gastroenterology 152:1933-1943.e5
Liu, Siyu; Barry, Elizabeth L; Baron, John A et al. (2017) Effects of supplemental calcium and vitamin D on the APC/?-catenin pathway in the normal colorectal mucosa of colorectal adenoma patients. Mol Carcinog 56:412-424
Anderson, Joseph C; Morris, Carolyn B; Robertson, Douglas J et al. (2017) Can the Sum of Adenoma Diameters (Adenoma Bulk) on Index Examination Predict Risk of Metachronous Advanced Neoplasia? J Clin Gastroenterol :
Rees, Judy R; Mott, Leila A; Barry, Elizabeth L et al. (2016) Randomized controlled trials: who fails run-in? Trials 17:374
Baron, John A; Barry, Elizabeth L; Mott, Leila A et al. (2015) A Trial of Calcium and Vitamin D for the Prevention of Colorectal Adenomas. N Engl J Med 373:1519-30
Peery, Anne F; Sandler, Robert S; Galanko, Joseph A et al. (2015) Risk Factors for Hemorrhoids on Screening Colonoscopy. PLoS One 10:e0139100
Obuch, Joshua C; Pigott, Courtney M; Ahnen, Dennis J (2015) Sessile serrated polyps: detection, eradication, and prevention of the evil twin. Curr Treat Options Gastroenterol 13:156-70
Barry, Elizabeth L; Rees, Judy R; Peacock, Janet L et al. (2014) Genetic variants in CYP2R1, CYP24A1, and VDR modify the efficacy of vitamin D3 supplementation for increasing serum 25-hydroxyvitamin D levels in a randomized controlled trial. J Clin Endocrinol Metab 99:E2133-7
Barry, Elizabeth L; Mott, Leila A; Melamed, Michal L et al. (2014) Calcium supplementation increases blood creatinine concentration in a randomized controlled trial. PLoS One 9:e108094

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