Clinical Trial: Calcium/Vitamin D, Biomarkers & Colon Polyp Prevention

Study Status: Completed
Recruit Status: Completed
Study Type: Observational

Official Title: Calcium/Vitamin D, Biomarkers & Colon Polyp Prevention

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 Summary:

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 r
Sponsor: Emory University

Current Primary Outcome:

  • COX-2 Levels [ Time Frame: Baseline to end of intervention (up to 5 years) ]
    Cyclo-oxygenase-2 (COX-2) is an enzyme that is elevated during periods of inflammation. Inflammation and inflammation regulation likely have important roles in colon cancer development. Control of inflammatory response suppresses COX-2.
  • APC Protein Levels [ Time Frame: Baseline to end of intervention (up to 5 years) ]
    Adenomatous polyposis coli (APC) is a protein encoded by the APC gene and is part of the APC Pathway of colon cancer development. The APC Pathway accounts for familial adenomatosis polyposis (FAP) and approximately 80% of sporadic cancers. The APC protein regulates β-catenin.
  • β-catenin Levels [ Time Frame: Baseline to end of intervention (up to 5 years) ]
    β-catenin is a protein encoded by the CTNNB1 gene and is part of the APC Pathway of colon cancer development. Overexpression and mutations of β-catenin are associated with multiple cancers, including colorectal cancer. An increase in the ratio of APC to β-catenin is indicative of a decrease of adenoma recurrence.
  • E-cadherin Levels [ Time Frame: Baseline to end of intervention (up to 5 years) ]
    E-cadherin is a calcium-dependent cell adhesion molecule necessary for colon crypt structure and function. Regulated by β-catenin, E-cadherin is part of the APC Pathway of colon cancer development. An increase in the ratio of APC to E-cadherin is indicative of a decrease of adenoma recurrence.
  • MLH1 Protein Levels [ Time&n

    Original Primary Outcome: Investigate the effect of calcium and/or vitamin D on a panel of biomarkers of risk for colorectal cancer, if the modification is associated with decreased recurrence adenomatous polyps.

    Current Secondary Outcome:

    Original Secondary Outcome:

    • To clarify differences among the treatment groups at the 3-5-year colonoscopies precede and may predict adenoma recurrence,
    • To clarify differences in the biomarkers in rectal mucosa among the treatment groups at the 3-5-year colonoscopies also occur more proximally in the colon,
    • To clarify differences in the biomarkers in rectal mucosa among the treatment groups at the 3-5-year colonoscopies are affected by colonoscopic preparation, and
    • To clarify differences in biomarkers from baseline to one year are maintained, accumulative, or attenuated by 3-5 years,
    • Estimate the normal variability of the biomarker panel in sporadic adenoma patients over time.
    • Investigate whether biomarker responses to treatments vary according to nonsteroidal anti-inflammatory drug (NSAID) use or vitamin D receptor (VDR) genotype.


    Information By: Emory University

    Dates:
    Date Received: November 13, 2006
    Date Started: June 2006
    Date Completion:
    Last Updated: December 7, 2016
    Last Verified: December 2016