Calcium/Vitamin D, Biomarkers & Colon Polyp Prevention

NCT ID: NCT00399607

Last Updated: 2016-12-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

264 participants

Study Classification

OBSERVATIONAL

Study Start Date

2006-06-30

Study Completion Date

2016-08-31

Brief Summary

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The study team has developed a set of biomarkers of risk for colon cancer; this study tests 1) whether or not calcium and/or vitamin D supplementation can favorably affect these biomarkers in persons who are at higher than average risk for colon cancer (ie, have already undergone the removal of colon growths, called adenomatous polyps, which are known to be precursors to developing colon cancer), and 2) whether effects on the biomarkers predict who will get new colon polyps or not.

Detailed Description

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This study is an add-on study ('adjunct study') to a clinical trial that is already being conducted (the 'parent study'). Study participants will be composed of persons who are already participating in the parent study, "Vitamin D/Calcium Polyp Prevention Study". In the parent study, a total of 1,964 people nationally are being randomly assigned to four different treatment groups: 1) calcium supplements, 600 mg twice a day; 2) vitamin D supplements, 500 IU twice a day; 3) both the calcium and vitamin D supplements twice a day; and 4) placebo tablets twice a day. The treatment period lasts three to five years at the end of which study participants undergo a follow-up colonoscopy to look for new polyps. The parent study began about a year prior to the start of this adjunct study, thus, there are already some patients in the trial who are receiving their study 'treatments' (i.e., have been 'randomized'), but more patients will be recruited into the parent study.

Depending on whether someone has already been randomized, participants of the parent study will be invited to take part in the adjunct study in one of two ways: 'Aim 1' only, or 'All Aims'. First, patients who have already been randomized will be asked to allow biopsies to be made of their rectal tissue during their 3- or 5-year follow-up colonoscopy (Aim 1). Biopsies, which will be used for our biomarker measurements, are very tiny pieces of tissue that can be examined under the microscope. Second, patients who have not yet been randomized will be invited to participate more fully (All Aims) in the adjunct study. This involves having outpatient rectal biopsies taken immediately after their first phone call, their 1-year follow-up visit, and 7 - 21 days before their 3- or 5-year follow-up colonoscopy. Finally, during their 3- or 5-year colonoscopy, biopsies will be taken from three areas of the colon: the rectum (same area as the outpatient biopsies), the sigmoid colon, and the ascending colon. From all of the biopsies taken from all of the visits and colon sites, biomarker measurements will be of normal proteins that occur in the surface cells lining the colon. Study researchers will then analyze whether calcium and/or vitamin D affect these biomarkers and whether the effects predict who gets new polyps.

Conditions

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Colorectal Adenomatous Polyps

Keywords

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colonic neoplasms colorectal adenoma calcium vitamin D

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

PROSPECTIVE

Study Groups

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Aim 1

Participants previously randomized for the parent study will be eligible for a portion of the adjunct biomarker study.

Rectal biopsy during colonoscopy

Intervention Type PROCEDURE

Biopsies of rectal tissue will be obtained during the 3 or 5 year follow-up colonoscopy. The collection of rectal biopsies involves inserting a tube-about as long and big around as a doctor's examining finger-through the anus into the rectum or lower colon to a depth of about 3-4 inches. At this spot, 4 - 6 tiny pinches of tissue one mm thick (less than 1/16 of an inch) will be taken. The procedure takes less than two minutes, is painless (the only discomfort is like that of having a rectal exam), and is very low risk-about like having blood drawn.

All aims

Participants entering the parent study will be eligible for all sample collections of the adjunct biomarker study.

Rectal biopsy at randomization

Intervention Type PROCEDURE

Biopsies of rectal tissue will be obtained at the time of randomization. The collection of rectal biopsies involves inserting a tube-about as long and big around as a doctor's examining finger-through the anus into the rectum or lower colon to a depth of about 3-4 inches. At this spot, 4 - 6 tiny pinches of tissue one mm thick (less than 1/16 of an inch) will be taken. The procedure takes less than two minutes, is painless (the only discomfort is like that of having a rectal exam), and is very low risk-about like having blood drawn.

Rectal biopsy at 1 year

Intervention Type PROCEDURE

Biopsies of rectal tissue will be obtained at the time of the one year follow-up visit. The collection of rectal biopsies involves inserting a tube-about as long and big around as a doctor's examining finger-through the anus into the rectum or lower colon to a depth of about 3-4 inches. At this spot, 4 - 6 tiny pinches of tissue one mm thick (less than 1/16 of an inch) will be taken. The procedure takes less than two minutes, is painless (the only discomfort is like that of having a rectal exam), and is very low risk-about like having blood drawn.

Rectal biopsy prior to colonoscopy

Intervention Type PROCEDURE

Biopsies of rectal tissue will be obtained 7-21 days prior to the 3 or 5 year colonoscopy. The collection of rectal biopsies involves inserting a tube-about as long and big around as a doctor's examining finger-through the anus into the rectum or lower colon to a depth of about 3-4 inches. At this spot, 4 - 6 tiny pinches of tissue one mm thick (less than 1/16 of an inch) will be taken. The procedure takes less than two minutes, is painless (the only discomfort is like that of having a rectal exam), and is very low risk-about like having blood drawn.

Biopsies during colonoscopy

Intervention Type PROCEDURE

Biopsies of the rectum, sigmoid colon and ascending colon will be obtained during the 3-5 year follow-up colonoscopy. The colonoscopy involves insertion of a flexible tube through the anus, which is then advanced the full length of the colon. Biopsies (tiny pinches of tissue less than 1/16 of an inch thick) will be taken as the colonoscopy tube is being removed. In total, 12-16 biopsies will be taken from the rectum (or lower colon about 3 - 4 inches up), sigmoid colon and ascending colon.

Interventions

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Rectal biopsy during colonoscopy

Biopsies of rectal tissue will be obtained during the 3 or 5 year follow-up colonoscopy. The collection of rectal biopsies involves inserting a tube-about as long and big around as a doctor's examining finger-through the anus into the rectum or lower colon to a depth of about 3-4 inches. At this spot, 4 - 6 tiny pinches of tissue one mm thick (less than 1/16 of an inch) will be taken. The procedure takes less than two minutes, is painless (the only discomfort is like that of having a rectal exam), and is very low risk-about like having blood drawn.

Intervention Type PROCEDURE

Rectal biopsy at randomization

Biopsies of rectal tissue will be obtained at the time of randomization. The collection of rectal biopsies involves inserting a tube-about as long and big around as a doctor's examining finger-through the anus into the rectum or lower colon to a depth of about 3-4 inches. At this spot, 4 - 6 tiny pinches of tissue one mm thick (less than 1/16 of an inch) will be taken. The procedure takes less than two minutes, is painless (the only discomfort is like that of having a rectal exam), and is very low risk-about like having blood drawn.

Intervention Type PROCEDURE

Rectal biopsy at 1 year

Biopsies of rectal tissue will be obtained at the time of the one year follow-up visit. The collection of rectal biopsies involves inserting a tube-about as long and big around as a doctor's examining finger-through the anus into the rectum or lower colon to a depth of about 3-4 inches. At this spot, 4 - 6 tiny pinches of tissue one mm thick (less than 1/16 of an inch) will be taken. The procedure takes less than two minutes, is painless (the only discomfort is like that of having a rectal exam), and is very low risk-about like having blood drawn.

Intervention Type PROCEDURE

Rectal biopsy prior to colonoscopy

Biopsies of rectal tissue will be obtained 7-21 days prior to the 3 or 5 year colonoscopy. The collection of rectal biopsies involves inserting a tube-about as long and big around as a doctor's examining finger-through the anus into the rectum or lower colon to a depth of about 3-4 inches. At this spot, 4 - 6 tiny pinches of tissue one mm thick (less than 1/16 of an inch) will be taken. The procedure takes less than two minutes, is painless (the only discomfort is like that of having a rectal exam), and is very low risk-about like having blood drawn.

Intervention Type PROCEDURE

Biopsies during colonoscopy

Biopsies of the rectum, sigmoid colon and ascending colon will be obtained during the 3-5 year follow-up colonoscopy. The colonoscopy involves insertion of a flexible tube through the anus, which is then advanced the full length of the colon. Biopsies (tiny pinches of tissue less than 1/16 of an inch thick) will be taken as the colonoscopy tube is being removed. In total, 12-16 biopsies will be taken from the rectum (or lower colon about 3 - 4 inches up), sigmoid colon and ascending colon.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* 45 - 75 years old.
* ≥ 1 histologically-verified neoplastic polyps, ≥ 2 mm in diameter, removed from the large bowel within 4 months of study entry, with entire large bowel examined by colonoscopy and documented free of further polyps.
* Willing to follow the study protocol, as indicated by the subject's 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.
* Anticipated colonoscopic follow up three years or five years after the qualifying colonoscopy.

Exclusion Criteria

* Invasive carcinoma in any colonic polyp removed.
* Familial colonic polyposis syndromes.
* Ulcerative colitis or Crohn's disease.
* Malabsorption syndrome (e.g., pancreatic insufficiency).
* History of large bowel resection for any reason.
* Diagnosed narcotic or alcohol dependence.
* Elevated serum calcium or creatinine, or supraphysiologic levels of 25(OH) vitamin D at study entry.
* Current use of thiazide diuretic in amount greater than the equivalent of 50 mg of hydrochlorothiazide.
* New York Heart Association Cardiovascular Disease functional class 3 or 4.
* On renal dialysis.
* History of kidney stones, unexplained hematuria, or sarcoidosis in the previous 20 years.
* Any history of hypo- or hyperparathyroidism.
* Unwilling to forgo individual calcium and vitamin D supplementation during the trial.
* Unwilling to forgo daily intake of more than a quart of milk (or equivalent in other dairy products) or daily dietary intake of vitamin D estimated to be greater than 400 IU.
* History of osteoporosis or other medical condition that may require supplemental calcium or vitamin D.
* Current use of bisphosphonates (eg, alendronate \[Fosamax\], risendronate \[Actonel\]).
* Current use of calcitonins (eg, Miacalcin).


* Unable to be off aspirin for 7 days.
* History of bleeding disorder or current use of anticoagulant medication.
Minimum Eligible Age

45 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Emory University

OTHER

Sponsor Role lead

Responsible Party

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Roberd Bostick, MD, MPH

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Roberd M Bostick, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

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USC/Norris Comprehensice Cancer Center

Los Angeles, California, United States

Site Status

University of Colorado Health Sciences Center

Denver, Colorado, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

University of Iowa Hospitals & Clinic

Iowa City, Iowa, United States

Site Status

University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

University of North Carolina

Chapel Hill, North Carolina, United States

Site Status

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

University of South Carolina

West Columbia, South Carolina, United States

Site Status

Countries

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United States

Other Identifiers

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R01CA114456

Identifier Type: NIH

Identifier Source: secondary_id

View Link

0975-2005

Identifier Type: OTHER

Identifier Source: secondary_id

IRB00000357

Identifier Type: -

Identifier Source: org_study_id