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

Pouchitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01202396
• Other study ID #: MEC-10-2-033
• Status: Not yet recruiting
• Phase: N/A
• First received: September 2, 2010
• Last updated: September 14, 2010
• Start date: November 2010
• Est. completion date: November 2015

Study information

• Verified date: September 2010
• Source: Maastricht University Medical Center
• Contact: D. Jonkers, PhD
• Phone: *31-43-3875021
• Email: d.jonkers[@]intmed.unimaas.nl
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: November 2015
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Observational Model: Case Control, Time Perspective: Prospective

Related Conditions & MeSH terms

• Pouchitis

Locations

Country	Name	City	State
Netherlands	Maastricht University Medical Center, div. Gastroenterology-Hepatology	Maastricht	Limburg

Sponsors (1)

Lead Sponsor	Collaborator
Maastricht University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Differences in the intestinal microbiota composition between pouch patients with and without pouchitis	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.	24 months.	No
Secondary	The expression of defensins in the intestinal mucosa	The mRNA expression levels of human alfa and beta-defensins in intestinal mucosal biopsies will be assessed by real time PCR	24 months	No
Secondary	The intestinal permeability	The epithelial integrity will be studied by the multiple sugar test to assess small intestinal and whole gut permeability.	24 months.	No
Secondary	Inflammatory mediators	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.	24 months	No
Secondary	The expression of tight-junction associated proteins	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.	24 months.	No