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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01202396
Recruitment Status : Unknown
Verified September 2010 by Maastricht University Medical Center.
Recruitment status was:  Not yet recruiting
First Posted : September 15, 2010
Last Update Posted : September 15, 2010
Information provided by:
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.

Condition or disease

Study Type : Observational
Estimated Enrollment : 30 participants
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
Study Start Date : November 2010
Estimated Primary Completion Date : November 2014
Estimated Study Completion Date : November 2015

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

Primary Outcome Measures :
  1. 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 :
  1. 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

  2. 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.

  3. 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.

  4. 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:   All
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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01202396

Contact: D. Jonkers, PhD *31-43-3875021
Contact: M. Pierik, PhD MD *31-43-3875021

Maastricht University Medical Center, div. Gastroenterology-Hepatology Not yet recruiting
Maastricht, Limburg, Netherlands, 6226AZ
Contact: D. Jonkers, PhD    *31-43-3875021   
Contact: M. Pierik, PhD MD    *31-43-3875021   
Sponsors and Collaborators
Maastricht University Medical Center
Principal Investigator: A. Masclee, Prof MD PhD Maastricht University Medical Center

Responsible Party: Prof. Dr. A. Masclee, Maastricht University Medical Center Identifier: NCT01202396     History of Changes
Other Study ID Numbers: MEC-10-2-033
First Posted: September 15, 2010    Key Record Dates
Last Update Posted: September 15, 2010
Last Verified: September 2010

Keywords provided by Maastricht University Medical Center:
ulcerative colitis
epithelial integrity

Additional relevant MeSH terms:
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Ileal Diseases