Endomicroscopy in IBD Patients

NCT ID: NCT01417728

Last Updated: 2020-12-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

50 participants

Study Classification

OBSERVATIONAL

Study Start Date

2011-05-31

Study Completion Date

2013-08-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Crohn's Disease Ulcerative Colitis

Keywords

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endomicroscopy inflammatory bowel disease mucosal healing infliximab

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

PROSPECTIVE

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

University of Erlangen-Nürnberg Medical School

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Department of Medicine I, University of Erlangen-Nuremberg

Erlangen, , Germany

Site Status

Countries

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Germany

References

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Hundorfean G, Chiriac MT, Mihai S, Hartmann A, Mudter J, Neurath MF. Development and Validation of a Confocal Laser Endomicroscopy-Based Score for In Vivo Assessment of Mucosal Healing in Ulcerative Colitis Patients. Inflamm Bowel Dis. 2017 Dec 19;24(1):35-44. doi: 10.1093/ibd/izx012.

Reference Type DERIVED
PMID: 29272480 (View on PubMed)

Other Identifiers

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Mudter2011

Identifier Type: -

Identifier Source: org_study_id