Overview

This trial is active, not recruiting.

Condition colorectal adenomatous polyps
Treatments rectal biopsy during colonoscopy, rectal biopsy at randomization, rectal biopsy at 1 year, rectal biopsy prior to colonoscopy, biopsies during colonoscopy
Sponsor Emory University
Collaborator National Cancer Institute (NCI)
Start date June 2006
End date February 2016
Trial size 264 participants
Trial identifier NCT00399607, 0975-2005, IRB00000357, R01CA114456

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Observational model case-only
Time perspective prospective
Arm
Participants previously randomized for the parent study will be eligible for a portion of the adjunct biomarker study.
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.
Participants entering the parent study will be eligible for all sample collections of the adjunct biomarker study.
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.
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.
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.
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.

Primary Outcomes

Measure
COX-2 Levels
time frame: Baseline to end of intervention (up to 5 years)
APC Protein Levels
time frame: Baseline to end of intervention (up to 5 years)
β-catenin Levels
time frame: Baseline to end of intervention (up to 5 years)
E-cadherin Levels
time frame: Baseline to end of intervention (up to 5 years)
MLH1 Protein Levels
time frame: Baseline to end of intervention (up to 5 years)
Bax Levels
time frame: Baseline to end of intervention (up to 5 years)
hTERT Levels
time frame: Baseline to end of intervention (up to 5 years)
Bcl-2 Levels
time frame: Baseline to end of intervention (up to 5 years)
TGFα Levels
time frame: Baseline to end of intervention (up to 5 years)
TGFβ1 Levels
time frame: Baseline to end of intervention (up to 5 years)

Eligibility Criteria

Male or female participants from 45 years up to 75 years old.

Currently participating in the parent study. Not open to people not already enrolled in the parent study. This sub-study is for the collection of biopsies only, while the parent study is for calcium and vitamin D to prevent reoccurrence of colon polyps. Inclusion Criteria for the parent study: - 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 for the parent study: - 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). Additional exclusion criteria for the adjunct biomarker study are: - Unable to be off aspirin for 7 days. - History of bleeding disorder or current use of anticoagulant medication.

Additional Information

Official title Calcium/Vitamin D, Biomarkers & Colon Polyp Prevention
Principal investigator Roberd M Bostick, MD, MPH
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in February 2016.
Information provided to ClinicalTrials.gov by Emory University.