Characterization of Crohn's Disease at Confocal Laser Endomicroscopy (CLE) and Related to Disease Activity

Study Overview
=================
Brief Summary
-----------------
A blinded prospective observation and methodology study with Confocal Laser Endomicroscopy (CLE) together with standard white light colonoscopy including inter- and intra-observation of patients with Crohn's disease.

Detailed Description
-----------------
Introduction: Crohn's disease is a well-characterized disease, and treatment is carried out according to international guidelines. Despite this, the disease often show an individual, unpredictable course, and more than half of patients experience significant complications of the disease. Endoscopy is important for the assessment of disease dissemination and severity of Crohn's disease, which is complemented by biochemical and clinical indices, including CDAI or Simple Index (SI) (Harwey-Bradshaw), which is internationally recognized. By CDAI, there is shown a good correlation with the biochemical activity markers such as CRP, and serum albumin, and in practice the simplified version (SI). Is often used. Knowledge about the use of CLE in Crohn's disease is very low. We will on the basis of parameters suggested in smaller studies and our personal CLE experience determine which parameters are useful for a precise estimation of the severity of Crohn's disease. Since the disease is most commonly seen in the terminal ileum, the parameters should apply to both the ileum and colon. A group Crohn patients have long been in prolonged biochemical and conventional endoscopic remission, including patients treated with the biologic drug infliximab. These patients are also included in the study as a particularly interesting subgroup as CLE in a small study has suggested to contribute to the safe discontinuation of immunosuppressive therapy. The degree of healing of the mucous membrane including an intact barrier function is one of the most important prognostic factors for patients to develop a recurrence. Thus it will be of great clinical importance to clarify whether CLE can help to distinguish those patients who have an apparently normal endoscopy, yet unrealized discrete activity and defective barrier function from patients where there is no activity evaluated endoscopically and by CLE. Furthermore, a small number of patients will be included as a control group. Hypothesis: CLE can characterize Crohn's disease and activity precisely in the ileum and colon compared with conventional ileocolonoscopy, including detecting slight degrees and wider dissemination of inflammation that would otherwise not be recognized. Design: A blinded prospective observation and method study of patients with subsequent calculation of intra-and inter-observer variability. Method: The patients enrolled including the control group, will be investigated respectively, by conventional colonoscopy and CLE in both the terminal ileum as colon. The degree and extent of Crohn's disease are assessed by conventional ileocolonoscopy (SI), CLE (selected parameters) and histology biopsies. Terminal ileum and each colonic segment (caecum, ascending colon, transversal colon, descending colon, colon sigmoid and rectum) are assessed as described above. Then, the correlation between histology (gold standard), SI and CLE is calculated. An intra-and inter-observer study follows on CLE parameters, where 3 observers are blinded with respect to each other. The pathologist is blinded to conventional and CLE parameters. CLE results are stratified in order to identify which of the recorded CLE parameters that correlate best with the two other methods, and thus are most suitable for the characterization and activity of Crohn's disease. Statistical method: To calculate the CLE-finding in relation to respectively, SI and histology we use Spearman correlation analysis. At the inter-and intra-observer study used weighted Kappa. Patient: A complete sample-size calculation has been made for the inter-and intra-observer study of the individual CLE parameters by 3 observers. For, if possible, to achieve a kappa value of 0.9 with a confidence interval of 0.05, there must be 122 observations. If we succeed in registering SI score, CLE parameters and taking tissue samples for pathology in all the above intestinal segments, there will be 7 observations for each patient who subsequently are assessed in relation to each of the parameters used in the study. If all ileocolonoscopy are completed and all CLE observations are possible to analyze just 18 patients need to be enrolled in the study. It is assumed, however, that there will only be 50% of the expected observations as some CLE observations will be unsatisfactory and some procedures will be interrupted. Thus, 36 patients shall be included in the study to achieve the desired strength, 10 of which are in the control group.

Official Title
-----------------
Characterization of Crohn's Disease at Confocal Laser Endomicroscopy and Related to Disease Activity

Conditions
-----------------
Crohn Disease

Intervention / Treatment
-----------------
* Device: CLE ileocolonoscopy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with Crohn's disease and involvement of the ileum and / or colon Patients must be of legal age Shall be given written consent Both patients with the activity of their disease patients in remission on biological treatment including can be included The control group will consist of patients without known or suspected IBD Exclusion Criteria: Increased p-creatinine Demonstrated allergy to fluorescein Pregnant woman Lactating woman

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CLE ileocolonoscopy on Crohn patients<br>Patients known with Crohn´s disease | Device: CLE ileocolonoscopy<br>* The patients enrolled including the control group, will be investigated respectively, by conventional colonoscopy and CLE in both the terminal ileum as colon. The degree and extent of Crohn's disease are assessed by conventional ileocolonoscopy (SI), CLE (selected parameters) and histology biopsies. Then, the correlation between histology (gold standard), SI and CLE is calculated. An intra-and inter-observer study follows on CLE parameters, where 3 observers are blinded with respect to each other. The pathologist is blinded to conventional and CLE parameters. CLE results are stratified in order to identify which of the recorded CLE parameters that correlate best with the two other methods.<br>* Other names: confocal laser endomiscoscopy colonoscopy;|
| Sham Comparator: CLE ileocolonoscopy on control patients<br>CLE ileocolonoscopy on patients without known IBD | Device: CLE ileocolonoscopy<br>* The patients enrolled including the control group, will be investigated respectively, by conventional colonoscopy and CLE in both the terminal ileum as colon. The degree and extent of Crohn's disease are assessed by conventional ileocolonoscopy (SI), CLE (selected parameters) and histology biopsies. Then, the correlation between histology (gold standard), SI and CLE is calculated. An intra-and inter-observer study follows on CLE parameters, where 3 observers are blinded with respect to each other. The pathologist is blinded to conventional and CLE parameters. CLE results are stratified in order to identify which of the recorded CLE parameters that correlate best with the two other methods.<br>* Other names: confocal laser endomiscoscopy colonoscopy;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CLE (CLE score) vs WL colonoscopy (SES-CD) | Findings in CLE are recorded regarding inflammation (crypt architecture, vessel architecture, barrier dysfunction and inflammatory cell invasion 1-3 points each) and compared with the findings of conventional colonoscopy ted Simple endoscopic score - Crohn´s disease (SES-CD), including observations for the control group | 1 year | 
| CLE (CLE-score) vs pathology score for inflammation | CLE (crypt architecture, vessel architecture, barrier dysfunction and inflammatory cell invasion 1-3 points each) and colonoscopy findings are compared with the pathological evaluation of the inflammation in the tissue samples (points from 1-3 by the severity). | 1 year | 
| CLE findings (CLE-score) and Intra-and inter-observer agreement | Intra-and inter-observer agreements between 3 operators at CLE findings are calculated by kappa statistics (crypt architecture, vessel architecture, barrier dysfunction and inflammatory cell invasion). | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Registering time of the procedure. | Registering time of the procedure. | 1 year | 
| Number of Adverse Events | Number of Adverse Events related to the procedure is registered | 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
confocal laser endomicroscopy, Crohn´disease