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Endomicroscopy in IBD Patients (EARLY)

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: NCT01417728
Recruitment Status : Unknown
Verified November 2012 by University of Erlangen-Nürnberg Medical School.
Recruitment status was:  Recruiting
First Posted : August 16, 2011
Last Update Posted : November 30, 2012
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
University of Erlangen-Nürnberg Medical School

Brief Summary:
The aim of the study is to analyze the mechanism of action of infliximab at the endomicroscopic level and to analyze mucosal healing - i.e. structural and functional changes in the mucosa in IBD patients - and associated processes such as permeability and bacterial invasion of the mucosa. In this study the role of the above mentioned parameters and further the establishment of endomicroscopic scores will serve to define new prognostic markers in view of long term remission upon infliximab treatment.

Condition or disease
Crohn's Disease Ulcerative Colitis

Detailed Description:

The main goal of treatment for Crohn's disease and ulcerative colitis has always been the induction and maintenance of symptomatic improvement or at best remission. There is recent evidence that with immunosuppression and treatment with infliximab a long-term healing of the bowel can be achieved and that this affects the clinical outcome of both Crohn's disease and ulcerative colitis. Chronic idiopathic inflammatory bowel diseases (IBDs) including Crohn's disease, ulcerative colitis and indeterminate colitis are characterised by the presence of extensive areas of ulceration and inflammation in the gut. These ulcerations are the origin of several complications e.g fistulas, toxic megacolon, perforation and bleeding or developing neoplasias.

Therefore effective treatment of IBD should imply thoroughly and, if possible, complete healing of bowel ulcerations in parallel with clinical remission. There is evidence that infliximab, an immunoglobulin G1 monoclonal antibody against tumour necrosis factor, not only rapidly improves symptoms in patients with refractory IBDs, but also induces mucosal healing of ileocolonic lesions by week 4 after intravenous administration. The key question of course is whether healing of the mucosa of the bowel improves also the microstructural level of the mucosa and submucosa and perhaps translocation of commensal bacteria and barrier function as well. The validity of healing and maintain microscopic healing of the bowel mucosa and submucosa still has to be shown. Clinical studies showed that infliximab heals the mucosa of the colon in up to 60% by 8 weeks and maintains this healing for al long period of time. Unfortunately treatments that heal the mucosa do not cure Crohn's disease or ulcerative colitis; however, they are associated with a prolongation of the symptom free interval in comparison with the non-healed bowel. This fact suggests that the disease mechanism in the mucosa does not disappear with macroscopic healing of the ulcers and that the intraluminal trigger ends up damaging the mucosa again. For the purpose of clinical trials mucosal healing was defined so far by macroscopic view on the mucosa during white light endoscopy.

A microscopic analysis of the microstructure for assessment of healing seems to be necessary, especially to define objective end points for infliximab therapy to prevent relapses and complications. It is known that mucosal healing does not always correlate with clinical remission, therefore a microscopic diagnosis of ongoing inflammation is necessary.

Recently, a miniaturized confocal microscope was developed which could be integrated in the distal tip of a conventional colonoscope. This new diagnostic technology for gastrointestinal endoscopy, denoted confocal endomicroscopy, allowed in vivo histology of the mucosal layer during ongoing colonoscopy. Furthermore, in patients screened for sporadic colorectal cancer, surface and subsurface analysis at cellular and subcellular resolution could be used to predict intraepithelial neoplasias (INs) with high accuracy. Endomicroscopic image acquisition is performed by placing the tip of the colonoscope in direct contact with the targeted tissue site and providing in this manner surface and subsurface imaging at the time of ongoing video colonoscopy. It allows the detailed analysis of colorectal crypt architecture, deep vascular net structure and detailed mucosal / submucosal analysis. Studies in patients with ulcerative colitis showed that this novel endoscopic approach allowed to diagnose flat intraepithelial neoplasias with a high degree of accuracy and thus emerges as a crucial innovative imaging technology in the colon. Here, we propose to analyze the mucosa of patients with Crohn´s disease and ulcerative colitis before and after infliximab therapy using endomicroscopy for analysing microscopic healing processes during ongoing endoscopy.

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Study Type : Observational
Estimated Enrollment : 50 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Endomicroscopy for Assessment of Structural and Functional Changes in IBD Patients Treated With Anti-TNFalpha - Insights in the Process in Mucosal Healing
Study Start Date : May 2011
Estimated Primary Completion Date : April 2013
Estimated Study Completion Date : August 2013

Resource links provided by the National Library of Medicine

Primary Outcome Measures :
  1. Assessment of mucosal healing changes by confocal laser endomicroscopy [ Time Frame: 1 year ]

    Endomicroscopy will be used to assess the mucosal structure before and after treatment.

    Further Parameters:

    • assessment of mucosal barrier function in vivo during ongoing endoscopy
    • epithelial cell structure (development of new tools to differentiate mucosal structures and cells), e.g. crypt distortion, crypt lumen
    • infiltration of mononuclear cells
    • translocation of bacteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
trusted IBD diagnosis (Crohn's disease of ulcerative colitis)

Inclusion criteria:

  • Indication for therapy with infliximab according to the current guidelines.

Exclusion criteria:

  • Inability to provide written informed consent
  • Pregnancy or breast-feeding
  • Severe uncontrolled coagulopathy
  • Impaired renal function
  • Known allergy to fluorescein

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): NCT01417728

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Department of Medicine I, University of Erlangen-Nuremberg Recruiting
Erlangen, Germany, 91054
Contact: Jonas Mudter, MD    004991318545017   
Principal Investigator: Jonas Mudter, MD         
Sponsors and Collaborators
University of Erlangen-Nürnberg Medical School
Merck Sharp & Dohme Corp.
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: University of Erlangen-Nürnberg Medical School Identifier: NCT01417728    
Other Study ID Numbers: Mudter2011
First Posted: August 16, 2011    Key Record Dates
Last Update Posted: November 30, 2012
Last Verified: November 2012
Keywords provided by University of Erlangen-Nürnberg Medical School:
inflammatory bowel disease
mucosal healing
Additional relevant MeSH terms:
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Crohn Disease
Colitis, Ulcerative
Inflammatory Bowel Diseases
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Colonic Diseases