Mucosal Gene Expression Defects in IBD

Mucosal Gene Expression Defects in Patients With Inflammatory Bowel Disease Before and After First Infliximab Therapy

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.

Study Overview

• Status: Completed
• Conditions: Inflammatory Bowel Diseases

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.

• Study Type: Observational
• Enrollment (Actual): 73

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Department of Gastroenterology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• 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.

Description

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:

-

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
inflammatory bowel disease; Patients with refractory inflammatory bowel disease (ulcerative colitis and Crohn's disease) before and after treatment with infliximab.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Gene expression profiles assessed with microarray	before and after infliximab treatment (4-6 wks)

Collaborators and Investigators

• Sponsor: KU Leuven
• Collaborators: Fund for Scientific Research, Flanders, Belgium
• Investigators: Study Director: Paul Rutgeerts, MD, PhD, University of Leuven

Publications and helpful links

General Publications

• Arijs I, Li K, Toedter G, Quintens R, Van Lommel L, Van Steen K, Leemans P, De Hertogh G, Lemaire K, Ferrante M, Schnitzler F, Thorrez L, Ma K, Song XY, Marano C, Van Assche G, Vermeire S, Geboes K, Schuit F, Baribaud F, Rutgeerts P. Mucosal gene signatures to predict response to infliximab in patients with ulcerative colitis. Gut. 2009 Dec;58(12):1612-9. doi: 10.1136/gut.2009.178665. Epub 2009 Aug 20.

Study record dates

Study Major Dates

• Study Start: July 1, 2004
• Primary Completion (Actual): February 1, 2008
• Study Completion (Actual): February 1, 2008

Study Registration Dates

• First Submitted: March 14, 2008
• First Submitted That Met QC Criteria: March 19, 2008
• First Posted (Estimate): March 20, 2008

Study Record Updates

• Last Update Posted (Estimate): October 22, 2012
• Last Update Submitted That Met QC Criteria: October 19, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: Inflammatory bowel disease; Infliximab; Gene expression microarray
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Intestinal Diseases
• Other Study ID Numbers: Array study IBD 1