Lay Summary

Proposal No. IBD-0063
Principal Investigator: Joseph Romagnuolo, M.D.
Current Applicant Organization:  Medical University of South Carolina (Charleston, U.S.A.)
Original Applicant Organization: University of Calgary (Canada)
Project Title: Capsule endoscopic findings and incidence of disease in first-degree relatives of Crohn’s patients with abnormal intestinal permeability
Period of Award: October 1, 2003 - March 31, 2007

Background and Significance: Relatives of Crohn’s disease (CD) patients have a higher risk of developing CD. About 10% of healthy relatives of patients with CD have a "leaky" or "permeable" barrier in their small bowel, allowing foreign proteins or bacteria to get deeper into the bowel wall than intended, which can cause inflammation and/or CD. One can assess for this "leakiness" using the lactose-mannitol (L/M) test, which involves eating different sugars and collecting a urine sample. The significance of an abnormal L/M test in a healthy person is uncertain. We do not know whether abnormal L/M testing is an early sign of CD, increases one’s risk for CD in the future, or might require some type of preventative treatment or diet. Current tests are not sensitive enough to identify subtle abnormalities in the small bowel, but capsule endoscopy (CE), a new technology involving swallowing a miniature capsule-sized camera with a wireless transmitter, images the small bowel with higher accuracy than conventional options (small bowel follow-through (SBFT)).

Hypothesis: First-degree relatives of CD patients with increased permeability to L/M will have a higher prevalence of CE abnormalities and a higher risk of clinical CD than those without.

Methods: Approximately 400 first-degree relatives under age 35 years will be identified through our CD database and undergo L/M testing. Eighty subjects will then be recruited (40 with and 40 without L/M abnormalities), and will undergo baseline history, physical, laboratory blood testing (including genetic testing). Each will then undergo CE, SBFT and colonoscopy with biopsies. A GI pathologist will read the specimens. Blood, tissue, and stool will be banked for further testing. Patients will undergo repeat L/M annually, and if positive, will undergo repeat CE. If symptoms suspicious for CD develop, a re-evaluation with CE, SBFT, and colonoscopy will be performed. All patients will have a repeat CE at 3 years.

Sample Size Calculation: The study will require 40 subjects in each group. Because 10% of first-degree relatives of CD patients have had L/M abnormalities in previous studies, we will need to screen about 400 relatives, using our 900-patient database.