Calcium/Vitamin D, Biomarkers & Colon Polyp Prevention
Condition: Colorectal Adenomatous Polyps
MeSH terms: Adenomatous Polyps; Polyps
Study type: Observational

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.
    

Intervention name(s): Rectal biopsy during colonoscopy; Rectal biopsy at randomization; Rectal biopsy at 1 year; Rectal biopsy prior to colonoscopy; Biopsies during colonoscopy
Intervention type(s): Procedure; Procedure; Procedure; Procedure; Procedure
Intervention description(s): 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.; 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.; 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.; 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 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.
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.
      
Biospecimen description: 
      Biopsies of normal-appearing rectal mucosa will be collected from participants in an
      associated parent study.
    
Keywords: colonic neoplasms; colorectal adenoma; calcium; vitamin D