The Interaction Between Intestinal Microbiota, Innate Defense and Epithelial Integrity in the Development of Pouchitis

• Conditions: Pouchitis

• Registration Number: NCT01202396
• Lead Sponsor: Maastricht University Medical Center

Brief Summary

Pouchitis is a common complication following proctocolectomy with ileal pouch anal anastomosis (IPAA) in patients with ulcerative colitis (UC). It affects the quality of life and can become a chronic problem. The aetiology of pouchitis is not completely understood. A crucial role of the intestinal microbiota has been suggested, but no causative agent has been identified so far. Furthermore, the defensin expression and the epithelial integrity are altered in inflammatory bowel diseases and may play an important role in the development of intestinal inflammation. Therefore, it has been hypothesized that the interaction between an altered microbiota composition, a defective epithelial integrity and changes in innate defense parameters such as defensins has a pivotal role in the development of pouchitis in UC patients.

Detailed Description

Not available

Study Timeline

• Status Verified: 2010-09
• Study First Submitted: 2010-09-02
• Study First Submitted QC: 2010-09-14
• Last Update Submitted: 2010-09-14
• Study First Posted: 2010-09-15
• Last Update Posted: 2010-09-15
• Study Start: 2010-11
• Primary Completion: 2014-11
• Study Completion: 2015-11

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• patients with ulcerative colitis undergoing a total colectomy with IPAA for steroid dependent disease, therapy-refractory disease, colorectal cancer or severe dysplasia
• 18-65 years of age

Exclusion Criteria

• unable to give informed consent
• pregnant or breastfeeding

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Differences in the intestinal microbiota composition between pouch patients with and without pouchitis	24 months.	A phylogenetic microarray will be used to characterize the luminal and mucosal microbiota composition (based on the SSU rRNA gene)of pouch patients with and without pouchitis. Anticipated results are the identification of specific bacterial profiles, genera and/or species dat are discriminating between subgroups.

Secondary Outcome Measures

Name	Time	Method
The intestinal permeability	24 months.	The epithelial integrity will be studied by the multiple sugar test to assess small intestinal and whole gut permeability.
Inflammatory mediators	24 months	Cytokine levels will be studied in serum and in intestinal biopsies. Furthermore, a histological evaluation and the MPO activity will be studied in these biopsies and calprotectin levels will be determined in 'fecal' sampels.
The expression of tight-junction associated proteins	24 months.	The intestinal tight junctions-associated proteins will be studied by immune staining of intestinal biopsies and mRNA levels in intestinal biopsies using real time PCR. Biopsies will be collected from standardised locations.
The expression of defensins in the intestinal mucosa	24 months	The mRNA expression levels of human alfa and beta-defensins in intestinal mucosal biopsies will be assessed by real time PCR

Trial Locations

Locations (1)

Maastricht University Medical Center, div. Gastroenterology-Hepatology; 🇳🇱 Maastricht, Limburg, Netherlands