Mucosal Gene Expression Defects in IBD

Inflammatory Bowel Diseases Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00639821
• Other study ID #: Array study IBD 1
• Status: Completed
• Phase: N/A
• First received: March 14, 2008
• Last updated: October 19, 2012
• Start date: July 2004
• Est. completion date: February 2008

Study information

• Verified date: October 2012
• Source: Katholieke Universiteit Leuven
• Contact: n/a
• Is FDA regulated: No
• Health authority: European Union: European Medicines AgencyBelgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 73
• Est. completion date: February 2008
• Est. primary completion date: February 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Inflammatory Bowel Diseases
• Intestinal Diseases

Locations

Country	Name	City	State
Belgium	Department of Gastroenterology	Leuven

Sponsors (2)

Lead Sponsor	Collaborator
Katholieke Universiteit Leuven	Fund for Scientific Research, Flanders, Belgium

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Gene expression profiles assessed with microarray		before and after infliximab treatment (4-6 wks)	No