The Interaction Between Intestinal Microbiota, Innate Defense and Epithelial Integrity in the Development of Pouchitis
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ClinicalTrials.gov Identifier: NCT01202396
Verified September 2010 by Maastricht University Medical Center. Recruitment status was: Not yet recruiting
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.
Differences in the intestinal microbiota composition between pouch patients with and without pouchitis [ Time Frame: 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
The expression of defensins in the intestinal mucosa [ Time Frame: 24 months ]
The mRNA expression levels of human alfa and beta-defensins in intestinal mucosal biopsies will be assessed by real time PCR
The intestinal permeability [ Time Frame: 24 months. ]
The epithelial integrity will be studied by the multiple sugar test to assess small intestinal and whole gut permeability.
Inflammatory mediators [ Time Frame: 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 [ Time Frame: 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.
Biospecimen Retention: Samples With DNA
In the prospective study the following biospecimens will be collected: faeces, serum, plasma, leucocytes, urine, intestinal biopsies and mucus
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Ages Eligible for Study:
18 Years to 65 Years (Adult)
Sexes Eligible for Study:
Accepts Healthy Volunteers:
Consecutive patients undergoing proctocolectomy with the construction of an ileal pouch anal anastomosis will be asked to participate in the study
patients with ulcerative colitis undergoing a total colectomy with IPAA for steroid dependent disease, therapy-refractory disease, colorectal cancer or severe dysplasia