Endomicroscopy in IBD Patients
Condition: Crohn's Disease; Ulcerative Colitis
MeSH terms: Crohn Disease
Study type: Observational

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.
    

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.
    

Observational model: Case-Only
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        trusted IBD diagnosis (Crohn's disease of ulcerative colitis)
      
Keywords: endomicroscopy; inflammatory bowel disease; mucosal healing; infliximab