Vitamin D/Calcium Polyp Prevention Study

NCT00153816 | Completed Phase 2 Results DMC

• 2 other identifiers: 5R01CA098286-035R01CA098286-10
• Study Type: interventional
• Target: 2,813
• Locations: 2 countries
• Sites: 11

Brief 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.

Conditions

Colorectal Cancer; Polyps; Adenomas

Keywords

Colorectal neoplasms; Adenomatous polyps

Outcome Measures

Primary Outcomes (1)

• Colorectal Adenomas

  1 to 10 years

Secondary Outcomes (1)

• Advanced Colorectal Lesions

  1 to 10 years

Study Arms (6)

Full Factorial Placebo

EXPERIMENTAL

subjects in 2X2 factorial design; randomized to daily placebo

Drug: placebo

Full Factorial Calcium

EXPERIMENTAL

subjects in 2X2 factorial design; randomized to daily 1200 mg as calcium carbonate

Drug: Calcium Carbonate

Full Factorial Vitamin D

EXPERIMENTAL

Subjects in 2X2 factorial design; randomized to daily 1000 IU vitamin D3

Drug: Vitamin D3

Full Factorial Calcium Plus Vitamin D

EXPERIMENTAL

Subjects in 2X2 factorial design; randomized to daily 1200 mg as calcium carbonate and 1000 IU vitamin D3

Drug: Calcium Carbonate; Drug: Vitamin D3

Two Arm Placebo

EXPERIMENTAL

Women choosing to take daily 1200 mg as calcium carbonate randomized to daily placebo

Drug: Calcium Carbonate

Two Arm Vitamin D

EXPERIMENTAL

Women choosing to take daily 1200 mg as calcium carbonate randomized to daily 1000 IU vitamin D3

Drug: Calcium Carbonate; Drug: Vitamin D3

Interventions

Calcium Carbonate DRUG

3 gm/daily; 1200 mg elemental calcium/daily; two tablets per day; 600 mg elemental calcium/tablet

Full Factorial Calcium; Full Factorial Calcium Plus Vitamin D; Two Arm Placebo; Two Arm Vitamin D

Vitamin D3 DRUG

1000 IU/daily; two tablets per day; 500 IU per tablet

Full Factorial Calcium Plus Vitamin D; Full Factorial Vitamin D; Two Arm Vitamin D

placebo DRUG

placebo; two tablets per day

Full Factorial Placebo

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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
• Any diagnosis of invasive carcinoma of the large bowel (even if confined to a polyp)

Sponsors & Collaborators

• Dartmouth-Hitchcock Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (11)

University of Southern California

Los Angeles, California, 90089, United States

Location

University of Colorado

Denver, Colorado, 80220, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03766, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

University of South Carolina

Columbia, South Carolina, 29203, United States

Location

University of Texas

Houston, Texas, 77030, United States

Location

University of Puerto Rico

San Juan, Puerto Rico

Location

Related Publications (13)

• Gibbs DC, Barry EL, Fedirko V, Baron JA, Bostick RM. Impact of Common Vitamin D-Binding Protein Isoforms on Supplemental Vitamin D3 and/or Calcium Effects on Colorectal Adenoma Recurrence Risk: A Secondary Analysis of a Randomized Clinical Trial. JAMA Oncol. 2023 Apr 1;9(4):546-551. doi: 10.1001/jamaoncol.2022.6924.

  PMID: 36701139 DERIVED

• Passarelli MN, Mott LA, Barry EL, Rees JR, Baron JA. Oral Antibiotics and Risk of New Colorectal Adenomas During Surveillance Follow-up. Cancer Epidemiol Biomarkers Prev. 2021 Oct;30(10):1974-1976. doi: 10.1158/1055-9965.EPI-21-0323. Epub 2021 Jul 21.

  PMID: 34289971 DERIVED

• Passarelli MN, Karagas MR, Mott LA, Rees JR, Barry EL, Baron JA. Risk of keratinocyte carcinomas with vitamin D and calcium supplementation: a secondary analysis of a randomized clinical trial. Am J Clin Nutr. 2020 Dec 10;112(6):1532-1539. doi: 10.1093/ajcn/nqaa267.

  PMID: 33022713 DERIVED

• Crockett SD, Barry EL, Mott LA, Ahnen DJ, Robertson DJ, Anderson JC, Wallace K, Burke CA, Bresalier RS, Figueiredo JC, Snover DC, Baron JA. Calcium and vitamin D supplementation and increased risk of serrated polyps: results from a randomised clinical trial. Gut. 2019 Mar;68(3):475-486. doi: 10.1136/gutjnl-2017-315242. Epub 2018 Mar 1.

  PMID: 29496722 DERIVED

• Anderson JC, Morris CB, Robertson DJ, Barry ELR, Figueiredo JC, Cruz-Correa M, Bostick RM, Ahnen DJ, Baron JA. Can the Sum of Adenoma Diameters (Adenoma Bulk) on Index Examination Predict Risk of Metachronous Advanced Neoplasia? J Clin Gastroenterol. 2018 Aug;52(7):628-634. doi: 10.1097/MCG.0000000000000899.

  PMID: 28767463 DERIVED

• Barry EL, Peacock JL, Rees JR, Bostick RM, Robertson DJ, Bresalier RS, Baron JA. Vitamin D Receptor Genotype, Vitamin D3 Supplementation, and Risk of Colorectal Adenomas: A Randomized Clinical Trial. JAMA Oncol. 2017 May 1;3(5):628-635. doi: 10.1001/jamaoncol.2016.5917.

  PMID: 27978548 DERIVED

• Rees JR, Mott LA, Barry EL, Baron JA, Bostick RM, Figueiredo JC, Bresalier RS, Robertson DJ, Peacock JL. Lifestyle and Other Factors Explain One-Half of the Variability in the Serum 25-Hydroxyvitamin D Response to Cholecalciferol Supplementation in Healthy Adults. J Nutr. 2016 Nov;146(11):2312-2324. doi: 10.3945/jn.116.236323. Epub 2016 Sep 28.

  PMID: 27683872 DERIVED

• Rees JR, Mott LA, Barry EL, Baron JA, Figueiredo JC, Robertson DJ, Bresalier RS, Peacock JL. Randomized controlled trials: who fails run-in? Trials. 2016 Jul 29;17:374. doi: 10.1186/s13063-016-1451-9.

  PMID: 27474021 DERIVED

• Baron JA, Barry EL, Mott LA, Rees JR, Sandler RS, Snover DC, Bostick RM, Ivanova A, Cole BF, Ahnen DJ, Beck GJ, Bresalier RS, Burke CA, Church TR, Cruz-Correa M, Figueiredo JC, Goodman M, Kim AS, Robertson DJ, Rothstein R, Shaukat A, Seabrook ME, Summers RW. A Trial of Calcium and Vitamin D for the Prevention of Colorectal Adenomas. N Engl J Med. 2015 Oct 15;373(16):1519-30. doi: 10.1056/NEJMoa1500409.

  PMID: 26465985 DERIVED

• Barry EL, Mott LA, Melamed ML, Rees JR, Ivanova A, Sandler RS, Ahnen DJ, Bresalier RS, Summers RW, Bostick RM, Baron JA. Calcium supplementation increases blood creatinine concentration in a randomized controlled trial. PLoS One. 2014 Oct 15;9(10):e108094. doi: 10.1371/journal.pone.0108094. eCollection 2014.

  PMID: 25329821 DERIVED

• Barry EL, Rees JR, Peacock JL, Mott LA, Amos CI, Bostick RM, Figueiredo JC, Ahnen DJ, Bresalier RS, Burke CA, Baron JA. 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. 2014 Oct;99(10):E2133-7. doi: 10.1210/jc.2014-1389. Epub 2014 Jul 29.

  PMID: 25070320 DERIVED

• Rees JR, Hendricks K, Barry EL, Peacock JL, Mott LA, Sandler RS, Bresalier RS, Goodman M, Bostick RM, Baron JA. Vitamin D3 supplementation and upper respiratory tract infections in a randomized, controlled trial. Clin Infect Dis. 2013 Nov;57(10):1384-92. doi: 10.1093/cid/cit549. Epub 2013 Sep 6.

  PMID: 24014734 DERIVED

• Bischoff-Ferrari HA, Rees JR, Grau MV, Barry E, Gui J, Baron JA. Effect of calcium supplementation on fracture risk: a double-blind randomized controlled trial. Am J Clin Nutr. 2008 Jun;87(6):1945-51. doi: 10.1093/ajcn/87.6.1945.

  PMID: 18541589 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Polyps; Adenoma; Adenomatous Polyps

Interventions

Calcium Carbonate; Cholecalciferol

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Calcium Compounds; Inorganic Chemicals; Carbonates; Carbonic Acid; Carbon Compounds, Inorganic; Minerals; Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Results Point of Contact

• Title: Leila A. Mott, Statistical Analyst
• Organization: Geisel School of Medicine at Dartmouth

Leila.A.Mott@Dartmouth.EDU

603-650-3447

Study Officials

• John A. Baron, MD

  Dartmouth-Hitchcock Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2005
• First Posted: September 12, 2005
• Study Start: July 1, 2004
• Primary Completion: October 1, 2013
• Study Completion: June 1, 2016
• Last Updated: March 15, 2017
• Results First Posted: October 20, 2015

Record last verified: 2017-02

Locations

PR (1); US (10)