Clinical trial NCT01738529: Characterization of Crohn's Disease at Confocal Laser Endomicroscopy (CLE) and Related to Disease Activity
Official title: Characterization of Crohn's Disease at Confocal Laser Endomicroscopy and Related to Disease Activity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Crohn Disease
Keywords: confocal laser endomicroscopy
Crohn´disease
Lead sponsor: Herlev Hospital
Sponsor class: OTHER
First posted: 2012-11-30
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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.

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

Primary outcomes:
measure: CLE (CLE score) vs WL colonoscopy (SES-CD)
timeFrame: 1 year
measure: CLE (CLE-score) vs pathology score for inflammation
timeFrame: 1 year
measure: CLE findings (CLE-score) and Intra-and inter-observer agreement
timeFrame: 1 year
Secondary outcomes:
measure: Registering time of the procedure.
timeFrame: 1 year
measure: Number of Adverse Events
timeFrame: 1 year
Other outcomes:
Locations:
city: Herlev
country: Denmark
facility: Copenhagen University Hospital Herlev
Study officials:
affiliation: Department of Gastroenterology
name: john g Karstensen, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Gastroenterology
name: peter vilmann, Prof.
role: STUDY_CHAIR
References:
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citation: Karstensen JG, Saftoiu A, Brynskov J, Hendel J, Klausen P, Cartana T, Klausen TW, Riis LB, Vilmann P. Confocal laser endomicroscopy: a novel method for prediction of relapse in Crohn's disease. Endoscopy. 2016 Apr;48(4):364-72. doi: 10.1055/s-0034-1393314. Epub 2015 Nov 19.