Total proctocolectomy and ileal pouch-anal anastomosis is the surgical treatment of choice for patients with medically refractory ulcerative colitis, ulcerative colitis with dysplasia or cancer, and patients with familial adenomatous polyposis. Pouchitis, an inflammatory process of the ileal pouch, is the most common long-term complication. Increased stool frequency, abdominal pain, and pelvic discomfort are common symptoms in patients with ileal pouch-anal anastomosis. While these symptoms may be suggestive of pouchitis, approximately 40% of patients with these symptoms have no or minimal inflammation of the pouch or rectal cuff on endoscopy and histopathology. These patients have a condition resembling irritable bowel syndrome (IBS), which we termed the irritable pouch syndrome (IPS). The RATIONALE and FEASIBILITY for the proposed study are: 1) IPS occurs in a substantial number of patients with IPAA, significantly affecting quality of life. However, IPS is rare in the general population, and is considered an orphan disease. Studies such as those we propose can only be conducted in centers with a large number of patients with IPAA. The Cleveland Clinic has maintained the world's largest ileal pouch registry, with a total of more than 2,500 patients; 2) a series of investigations on the diagnosis and treatment of patients with inflammatory or functional diseases of IPS, notably the initial study of IPS, have been conducted by our team; 3) In contrast to IBS, the pathophysiology and treatment of IPS have not been studied. Our HYPOTHESES are that 1) similar to IBS, visceral hypersensitivity may play a role in the pathogenesis of IPS, and 2) amitriptyline, a safe and effective agent for patients with IBS, will be more effective than placebo in alleviating symptoms and improving quality of life in patients with IPS.
The AIMS of study are to 1) investigate visceral hypersensitivity using barostat examination of the pouch; 2) conduct a randomized, placebo-controlled clinical trial evaluating the use of amitriptyline in IPS.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Small Research Grants (R03)
Project #
1R03DK067275-01
Application #
6757605
Study Section
Special Emphasis Panel (ZDK1-GRB-9 (J1))
Program Officer
Robuck, Patricia R
Project Start
2004-04-01
Project End
2006-03-31
Budget Start
2004-04-01
Budget End
2005-03-31
Support Year
1
Fiscal Year
2004
Total Cost
$149,000
Indirect Cost
Name
Cleveland Clinic Lerner
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
135781701
City
Cleveland
State
OH
Country
United States
Zip Code
44195
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Navaneethan, Udayakumar; Shen, Bo (2009) Laboratory tests for patients with ileal pouch-anal anastomosis: clinical utility in predicting, diagnosing, and monitoring pouch disorders. Am J Gastroenterol 104:2606-15
Navaneethan, Udayakumar; Remzi, Feza H; Nutter, Benjamin et al. (2009) Risk factors for abnormal liver function tests in patients with ileal pouch-anal anastomosis for underlying inflammatory bowel disease. Am J Gastroenterol 104:2467-75
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Shen, Bo; Remzi, Feza H; Brzezinski, Aaron et al. (2008) Risk factors for pouch failure in patients with different phenotypes of Crohn's disease of the pouch. Inflamm Bowel Dis 14:942-8
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Shen, Bo; Liu, Wendy; Remzi, Feza H et al. (2008) Enterochromaffin cell hyperplasia in irritable pouch syndrome. Am J Gastroenterol 103:2293-300

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