Mucosal Gene Expression Defects in IBD

This study has been completed.
Sponsor:
Collaborator:
Fund for Scientific Research, Flanders, Belgium
Information provided by (Responsible Party):
Paul Rutgeerts, Katholieke Universiteit Leuven
ClinicalTrials.gov Identifier:
NCT00639821
First received: March 14, 2008
Last updated: October 19, 2012
Last verified: October 2012
  Purpose

This study investigated the mucosal gene expression defects associated with active Crohn's disease (CD)and ulcerative colitis (UC), and studied the effect of infliximab induced downregulation of inflammation and mucosal healing on these abnormalities, using whole genome gene expression microarrays.


Condition
Inflammatory Bowel Diseases

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Mucosal Gene Expression Defects in Patients With Inflammatory Bowel Disease Before and After First Infliximab Therapy

Resource links provided by NLM:


Further study details as provided by Katholieke Universiteit Leuven:

Primary Outcome Measures:
  • Gene expression profiles assessed with microarray [ Time Frame: before and after infliximab treatment (4-6 wks) ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples Without DNA

Ileal/colonic mucosal biopsies from patiens with inflammatory bowel disease refractory to corticosteroids and/or immunosuppression and from 12 control individuals


Enrollment: 73
Study Start Date: July 2004
Study Completion Date: February 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Groups/Cohorts
inflammatory bowel disease
Patients with refractory inflammatory bowel disease (ulcerative colitis and Crohn's disease) before and after treatment with infliximab.

Detailed Description:

Infliximab, a monoclonal IgG1 antibody to the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α), was the first efficacious biological therapy for IBD. Infliximab dramatically improved the quality of life in IBD patients. Besides inducing and maintaining remission in refractory IBD patients, infliximab has achieved new treatment goals such as intestinal mucosal healing and a reduction in hospitalizations and surgeries on the long-term. However, up to 30% of IBD patients do not respond to this costly therapy and potentially harmful therapy, and in an extra 20-30% response is incomplete. The mechanism of resistance to infliximab is unknown and predictors of response to infliximab are currently lacking.

The aim of this study was to investigate the mucosal gene expression defects associated with active Crohn's disease (CD)and ulcerative colitis (UC), and to study the effect of infliximab induced downregulation of inflammation and mucosal healing on these abnormalities, using whole genome gene expression microarray technology on endoscopic-derived intestinal mucosal biopsies from control individuals and patients with active IBD, and this before and after their first infliximab treatment.

Sixty-one patients with inflammatory bowel disease, 19 with Crohn's colitis, 18 with Crohn's ileitis and 24 with UC, undergo a colonoscopy with biopsies before and 4-6 weeks after the first infliximab treatment. Response to infliximab was defined based on endoscopic and histologic findings. A control group of 12 individuals was also included.Total RNA was isolated from biopsies, labelled and hybridized to Affymetrix HGU133plus2.0 Array. Microarray data were analyzed using Bioconductor software and Ingenuity Pathway Analysis software. Quantitative real time RT-PCR and immunohistochemistry were used to confirm microarray data.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Colonic mucosal biopsies from patients with refractory inflammatory bowel disease who had never been treated with biological therapy.

Criteria

Inclusion Criteria:

  • Clinical diagnosis of inflammatory bowel disease (Crohn's disease or ulcerative colitis)
  • Patients with inflammatory bowel disease refractory to corticosteroids and/or immunosuppression who had never been treated with biological therapy (anti-TNF treatment).

Exclusion Criteria:

-

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00639821

Locations
Belgium
Department of Gastroenterology
Leuven, Belgium, 3000
Sponsors and Collaborators
Katholieke Universiteit Leuven
Fund for Scientific Research, Flanders, Belgium
Investigators
Study Director: Paul Rutgeerts, MD, PhD University of Leuven
  More Information

No publications provided by Katholieke Universiteit Leuven

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Paul Rutgeerts, MD, PhD, Katholieke Universiteit Leuven
ClinicalTrials.gov Identifier: NCT00639821     History of Changes
Other Study ID Numbers: Array study IBD 1
Study First Received: March 14, 2008
Last Updated: October 19, 2012
Health Authority: European Union: European Medicines Agency
Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment

Keywords provided by Katholieke Universiteit Leuven:
Gene expression microarray
Inflammatory bowel disease
Infliximab

Additional relevant MeSH terms:
Inflammatory Bowel Diseases
Intestinal Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Infliximab
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Dermatologic Agents
Gastrointestinal Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 21, 2014