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

This study is not yet open for participant recruitment. (see Contacts and Locations)

Verified September 2010 by Maastricht University Medical Center

Sponsor:

Information provided by:

Maastricht University Medical Center

ClinicalTrials.gov Identifier:

NCT01202396

First received: September 2, 2010

Last updated: September 14, 2010

Last verified: September 2010

History of Changes

Purpose

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.

Condition
Pouchitis


Study Type:	Observational
Study Design:	Observational Model: Case Control Time Perspective: Prospective
Official Title:	The Interaction Between the Intestinal Microbiota, Innate Defense and Epithelial Integrity in the Development of Pouchitis: a Multifactorial Approach

Resource links provided by NLM:

Genetics Home Reference related topics: ulcerative colitis

MedlinePlus related topics: Drug Reactions Ulcerative Colitis

U.S. FDA Resources

Further study details as provided by Maastricht University Medical Center:

Primary Outcome Measures:

Differences in the intestinal microbiota composition between pouch patients with and without pouchitis [ Time Frame: 24 months. ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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. ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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. ] [ Designated as safety issue: No ]
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


Estimated Enrollment:	30
Study Start Date:	November 2010
Estimated Study Completion Date:	November 2015
Estimated Primary Completion Date:	November 2014 (Final data collection date for primary outcome measure)

Groups/Cohorts
ulcerative colitis patients with a pouch ulcerative colitis patients undergoing proctocolectomy with an ileal pouch anal anastomosis comparing patients with versus those without pouchitis no intervention

Eligibility


Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

Consecutive patients undergoing proctocolectomy with the construction of an ileal pouch anal anastomosis will be asked to participate in the study

Criteria

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01202396

Contacts


Contact: D. Jonkers, PhD	*31-43-3875021	d.jonkers@intmed.unimaas.nl
Contact: M. Pierik, PhD MD	*31-43-3875021	m.pierik@mumc.nl

Locations


Netherlands
Maastricht University Medical Center, div. Gastroenterology-Hepatology	Not yet recruiting
Maastricht, Limburg, Netherlands, 6226AZ
Contact: D. Jonkers, PhD *31-43-3875021 d.jonkers@intmed.unimaas.nl
Contact: M. Pierik, PhD MD *31-43-3875021 m.pierik@mumc.nl

Sponsors and Collaborators

Maastricht University Medical Center

Investigators


Principal Investigator:	A. Masclee, Prof MD PhD	Maastricht University Medical Center

More Information

No publications provided


Responsible Party:	Prof. Dr. A. Masclee, Maastricht University Medical Center
ClinicalTrials.gov Identifier:	NCT01202396 History of Changes
Other Study ID Numbers:	MEC-10-2-033
Study First Received:	September 2, 2010
Last Updated:	September 14, 2010
Health Authority:	Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Maastricht University Medical Center:


pouch pouchitis ulcerative colitis	microbiota defensins epithelial integrity

Additional relevant MeSH terms:


Pouchitis Digestive System Diseases Enteritis Gastroenteritis	Gastrointestinal Diseases Ileal Diseases Ileitis Intestinal Diseases

ClinicalTrials.gov processed this record on February 26, 2015

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