Colorectal CancerPhase 2/3NCT00153816
Vitamin D/Calcium Polyp Prevention Study
A Phase 2/3 study testing Calcium Carbonate and Vitamin D3 in people with Colorectal Cancer and Polyps, run by Dartmouth-Hitchcock Medical Center at 11 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 45 to 75 years
- Conditions the study is for
- Colorectal Cancer, Polyps, Adenomas
- What is being tested?
- Calcium Carbonate and Vitamin D3
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2,813 participants
- Where
- 11 sitesin 2 countries
- Study dates
- Jul 2004to Jun 2016
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Show all 13Show fewer
- 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
Who cannot join
- 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
Show all 37Show fewer
- 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
Trial locations and contacts
11 sites in 2 countries.
11 sites in 2 countries
United States10 sites
Emory University
Atlanta, Georgia, 30322
University of North Carolina
Chapel Hill, North Carolina, 27599
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
University of South Carolina
Columbia, South Carolina, 29203
University of Colorado
Denver, Colorado, 80220
University of Texas
Houston, Texas, 77030
University of Iowa
Iowa City, Iowa, 52242
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, 03766
University of Southern California
Los Angeles, California, 90089
University of Minnesota
Minneapolis, Minnesota, 55455
About this study
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.
Read the 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 11 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 partial 2 x 2 factorial design to vitamin D (1000 IU/day), calcium carbonate (1200 mg elemental calcium/day), both agents, or placebo only (Full Factorial randomization). Women who decline to forego calcium supplementation will be randomized only to calcium alone or to calcium plus vitamin D (Two Arm randomization). 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 up to 3000 participants to reach a total of up to 2400 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 primary 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 adenomas 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 no vitamin D (with or without calcium), between subjects randomized to calcium (with or without vitamin D) versus those randomized to no calcium (with or without vitamin D; excluding women electing to receive calcium who 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 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 as a secondary outcome. Participants will be invited to participate in an optional Observational Follow Up phase of the study that will begin following the end of treatment. In this phase of the study, subjects will continue to be followed on an observational basis (no study treatment) with annual questionnaires until the time of a subsequent colonoscopy that is at least three years from the follow up colonoscopy at which study treatment was ended. We will examine the occurrence of new adenomas in the interval between the colonoscopy exam at the end of study treatment and the exam at the end of observational follow up period.
- Conditions
- Colorectal Cancer, Polyps, Adenomas
- Being tested
- Calcium Carbonate, Vitamin D3, placebo
- Keywords
- Colorectal neoplasms, Adenomatous polyps
- Medical subject headings
- Colorectal Neoplasms, Polyps, Adenoma, Adenomatous Polyps
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Calcium CarbonateDrug
3 gm/daily; 1200 mg elemental calcium/daily; two tablets per day; 600 mg elemental calcium/tablet
Vitamin D3Drug
1000 IU/daily; two tablets per day; 500 IU per tablet
placeboDrug
placebo; two tablets per day
| Study group | Role | What they receive |
|---|---|---|
| Full Factorial Placebo | Experimental | subjects in 2X2 factorial design; randomized to daily placebo Receives: Drug: placebo |
| Full Factorial Calcium | Experimental | subjects in 2X2 factorial design; randomized to daily 1200 mg as calcium carbonate Receives: Drug: Calcium Carbonate |
| Full Factorial Vitamin D | Experimental | Subjects in 2X2 factorial design; randomized to daily 1000 IU vitamin D3 Receives: 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 Receives: Drug: Calcium Carbonate; Drug: Vitamin D3 |
| Two Arm Placebo | Experimental | Women choosing to take daily 1200 mg as calcium carbonate randomized to daily placebo Receives: 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 Receives: Drug: Calcium Carbonate; Drug: Vitamin D3 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Colorectal Adenomas
Measured: 1 to 10 years
Secondary outcomes (1)
Advanced Colorectal Lesions
Includes: adenomas >=1 cm, adenomas with high grade dysplasia, adenomas with villous features, or cancer.
Measured: 1 to 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2005 (estimated)
- Study startJul 2004
- Primary completionOct 2013
- Study completionJun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 2,813 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dartmouth-Hitchcock Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- John A. Baron, MD, Principal investigator, Dartmouth-Hitchcock Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00153816
- Sponsor's protocol ID
- 5R01CA098286-03
- Other IDs
- 5R01CA098286-10
- Status last verified
- Feb 2017
- First submitted
- 7 Sep 2005
- Last updated
- 15 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 36701139Passarelli 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.
PubMed 34289971Passarelli 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.
PubMed 33022713Crockett 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.
PubMed 29496722Anderson 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.
PubMed 28767463Barry 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.
PubMed 27978548Rees 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.
PubMed 27683872Rees 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.
PubMed 27474021Baron 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.
PubMed 26465985Barry 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.
PubMed 25329821Barry 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.
PubMed 25070320Rees 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.
PubMed 24014734Bischoff-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.
PubMed 18541589
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vitamin D/Calcium Polyp Prevention Study
- ClinicalTrials.gov ID
- NCT00153816
- Acronym / sponsor ID
- 5R01CA098286-03
- Conditions
- Colorectal Cancer, Polyps, Adenomas
- Keywords
- Colorectal neoplasms, Adenomatous polyps
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2,813 participants (actual)
- Lead sponsor
- Dartmouth-Hitchcock Medical CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Jul 2004 (actual)
- Primary completion
- Oct 2013 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 12 Sep 2005 (estimated)
- Results
- Posted 20 Oct 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 11 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 partial 2 x 2 factorial design to vitamin D (1000 IU/day), calcium carbonate (1200 mg elemental calcium/day), both agents, or placebo only (Full Factorial randomization). Women who decline to forego calcium supplementation will be randomized only to calcium alone or to calcium plus vitamin D (Two Arm randomization). 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 up to 3000 participants to reach a total of up to 2400 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 primary 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 adenomas 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 no vitamin D (with or without calcium), between subjects randomized to calcium (with or without vitamin D) versus those randomized to no calcium (with or without vitamin D; excluding women electing to receive calcium who 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 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 as a secondary outcome. Participants will be invited to participate in an optional Observational Follow Up phase of the study that will begin following the end of treatment. In this phase of the study, subjects will continue to be followed on an observational basis (no study treatment) with annual questionnaires until the time of a subsequent colonoscopy that is at least three years from the follow up colonoscopy at which study treatment was ended. We will examine the occurrence of new adenomas in the interval between the colonoscopy exam at the end of study treatment and the exam at the end of observational follow up period.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Full Factorial Placebo | Experimental | Drug: placebosubjects in 2X2 factorial design; randomized to daily placebo |
| Full Factorial Calcium | Experimental | Drug: Calcium Carbonatesubjects in 2X2 factorial design; randomized to daily 1200 mg as calcium carbonate |
| Full Factorial Vitamin D | Experimental | Drug: Vitamin D3Subjects in 2X2 factorial design; randomized to daily 1000 IU vitamin D3 |
| Full Factorial Calcium Plus Vitamin D | Experimental | Drug: Calcium Carbonate, Drug: Vitamin D3Subjects in 2X2 factorial design; randomized to daily 1200 mg as calcium carbonate and 1000 IU vitamin D3 |
| Two Arm Placebo | Experimental | Drug: Calcium CarbonateWomen choosing to take daily 1200 mg as calcium carbonate randomized to daily placebo |
| Two Arm Vitamin D | Experimental | Drug: Calcium Carbonate, Drug: Vitamin D3Women choosing to take daily 1200 mg as calcium carbonate randomized to daily 1000 IU vitamin D3 |
Who may qualify
- Ages
- 45 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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)
Key exclusion criteria (37 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Calcium Carbonate3 gm/daily; 1200 mg elemental calcium/daily; two tablets per day; 600 mg elemental calcium/tablet | Drug | Full Factorial Calcium, Full Factorial Calcium Plus Vitamin D, Two Arm Placebo, Two Arm Vitamin D |
| Vitamin D31000 IU/daily; two tablets per day; 500 IU per tablet | Drug | Full Factorial Calcium Plus Vitamin D, Full Factorial Vitamin D, Two Arm Vitamin D |
| placeboplacebo; two tablets per day | Drug | Full Factorial Placebo |
Primary outcome
Colorectal Adenomas
Time frame: 1 to 10 years
1 secondary outcome
Advanced Colorectal Lesions
Time frame: 1 to 10 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36701139Gibbs 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.
- Derived from this study: PubMed 34289971Passarelli 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.
- Derived from this study: PubMed 33022713Passarelli 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.
- Derived from this study: PubMed 29496722Crockett 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.
- Derived from this study: PubMed 28767463Anderson 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.
- Derived from this study: PubMed 27978548Barry 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.
- Derived from this study: PubMed 27683872Rees 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.
- Derived from this study: PubMed 27474021Rees 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.
- Derived from this study: PubMed 26465985Baron 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.
- Derived from this study: PubMed 25329821Barry 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.
- Derived from this study: PubMed 25070320Barry 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.
- Derived from this study: PubMed 24014734Rees 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John A. Baron, MD principal investigator
Dartmouth-Hitchcock Medical Center
11 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Calcium Carbonate and Vitamin D3 in people with Colorectal Cancer and Polyps, run by Dartmouth-Hitchcock Medical Center at 11 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Oct 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Colorectal Adenomas (time frame: 1 to 10 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00153816, which also lists 13 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2017.