Clinical trial NCT00399607: Calcium/Vitamin D, Biomarkers & Colon Polyp Prevention
Official title: Calcium/Vitamin D, Biomarkers & Colon Polyp Prevention
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Colorectal Adenomatous Polyps
Keywords: colonic neoplasms
colorectal adenoma
calcium
vitamin D
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-11-15
Enrollment: 264
Sex: ALL
Minimum age (years): 45
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants in the parent study examining the impact of calcium and vitamin D supplementation on the reoccurrence of colon polyps will be provided the opportunity to also participate in this adjunct biomarker study.

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: COX-2 Levels
timeFrame: Baseline to end of intervention (up to 5 years)
measure: APC Protein Levels
timeFrame: Baseline to end of intervention (up to 5 years)
measure: β-catenin Levels
timeFrame: Baseline to end of intervention (up to 5 years)
measure: E-cadherin Levels
timeFrame: Baseline to end of intervention (up to 5 years)
measure: MLH1 Protein Levels
timeFrame: Baseline to end of intervention (up to 5 years)
measure: Bax Levels
timeFrame: Baseline to end of intervention (up to 5 years)
measure: hTERT Levels
timeFrame: Baseline to end of intervention (up to 5 years)
measure: Bcl-2 Levels
timeFrame: Baseline to end of intervention (up to 5 years)
measure: TGFα Levels
timeFrame: Baseline to end of intervention (up to 5 years)
measure: TGFβ1 Levels
timeFrame: Baseline to end of intervention (up to 5 years)
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles-
country: United States
facility: USC/Norris Comprehensice Cancer Center
state: California
city: Denver
country: United States
facility: University of Colorado Health Sciences Center
state: Colorado
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Iowa City
country: United States
facility: University of Iowa Hospitals & Clinic
state: Iowa
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: West Columbia
country: United States
facility: University of South Carolina
state: South Carolina
Study officials:
affiliation: Emory University
name: Roberd M Bostick, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: