Clinical trial NCT02193802: Role of Capsule Endoscopy in the Evaluation of Mucosal Changes During Treatment of Patients With Active Crohn's Disease
Official title: Role of Capsule Endoscopy in the Evaluation of Mucosal Changes During Treatment of Patients With Active Crohn's Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Crohn's Disease
Keywords: Crohn's disease
small bowel (SB)
capsule endoscopy
ileocolonoscopy
anti-TNF-alpha antibodies
Lead sponsor: Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives
Sponsor class: OTHER
First posted: 2014-07-18
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: The utility of capsule endoscopy in diagnosing small bowel (SB) Crohn's disease has been demonstrated in a number of studies.

Mucosal healing is a good predictor of long term remission. Unfortunately, the assessment of small bowel mucosal healing by conventional colonoscopy is an invasive technique which is not complete since it does not allow exploration of the small bowel beyond the terminal ileum (TI). Thus, direct evidence of the healing of the majority of the small bowel is lacking.

Detailed description: Crohn's disease is a chronic, inflammatory disorder affecting any part of the gastrointestinal tract but the terminal ileum is the most frequent location involved alone or in combination with other locations. While about one half of patients have involvement of the ileum and large bowel, another third have disease limited to the small bowel.

The disease affects populations around the globe and occurs at any age but tends to have a peak incidence between the ages of 15 and 35. Typical presenting symptoms include abdominal pain and diarrhea. The clinical presentation of Crohn's disease fluctuates throughout the course of the disease. Symptoms and signs usually correlate with mucosal inflammation. The pattern of Crohn's disease viewed on endoscopy has been characterized and is associated with a number of mucosal characteristics such as erythema, swelling, nodularity, strictures, aphthoid ulceration and ulcers of variable size and depth.

The utility of capsule endoscopy in diagnosing small bowel (SB) Crohn's disease has been demonstrated in a number of studies. Diagnostic yields of 70% have been reported in suspected SB Crohn's disease. In patients with a known Crohn's disease, the superiority of the capsule to detect mucosal lesions of the SB in comparison to any other radiologic technique has also been clearly demonstrated.

A number of studies indicate that mucosal healing is a good predictor of long term remission. In particular, intense therapeutic regimens including purine analogues and biologic therapies like infliximab have been associated with endoscopic mucosal healing. The recently published SONIC trial evaluated the efficacy of infliximab monotherapy, azathioprine monotherapy and the two drugs combined in moderate to severe Crohn's disease patients. Patients who were treated with infliximab monotherapy and with the combination therapy had significantly longer corticosteroid-free clinical remission than those receiving azathioprine alone. Furthermore, mucosal healing, defined as the absence of mucosal ulcerations at week 26, was greater for the combination therapy than each of the monotherapies alone. Based on the results of these studies, obtaining a mucosal healing becomes in clinical practice a new therapeutic objective especially in patients treated by immunosuppressors or anti-TNF-alpha antibodies. In most of the studies, a complete mucosal healing was assessed by the complete disappearance of ulceration. An endoscopic response could be evaluated by the variation of several endoscopic scores of severity, that are either dedicated to the terminal ileon (TI) more the colon i.e. the Crohn's disease endoscopic severity index (CDEIS) or to the SB i.e. the Lewis score. Concerning the evaluation of the mucosal lesions of the SB by the capsule, a new index of severity is being developed in a study conducted by the different centers of the GETAID i.e. the CE-CDEIS. This score will be available in the first semester of 2013 and would be usable for the present study.

Unfortunately, the assessment of mucosal healing by conventional ileocolonoscopy is not complete since it does not allow exploration of the small bowel beyond TI. Thus, while mucosal changes and symptomatic improvement in subjects with SB Crohn's disease (with or without colonic involvement) can be inferred from studies like ACCENT I, direct evidence of the healing of the majority of the small bowel is lacking. In addition, correlation between evidence of mucosal healing and symptoms, as measured by the Crohn's Disease Activity Index (CDAI), has not been found reliable. This may reflect the limitation of viewing the full extent of small bowel ulcerations on the limited examination which is possible with ileocolonoscopy. This may potentially be overcome with the use of capsule endoscopy of the small bowel.

Until now, no study has evaluated the potential treatment-induced changes of the mucosal lesions located in the SB with a capsule and no comparison between the capsule and the ileocolonoscopy has been conducted in the evaluation of the TI which is the segment analyzable by both techniques. For the patients, demonstrate that the capsule is usable to evaluate the mucosal healing, would be a considerable benefit knowing that the capsule do not necessitate an arduous bowel cleansing and a sedation or a general anesthesia.

The proposed study is designed as a pilot study to evaluate the role of capsule endoscopy in Crohn's disease patients, in monitoring the changes in the terminal ileum and small bowel mucosa during Crohn's disease treatment for induction of remission in active Crohn's disease with ileal involvement. Success in this trial may lead to a larger trial to validate the findings.

Eligibility criteria: Inclusion Criteria:

* Subject aged more than 18 years
* Subject with at least ileal lesions of Crohn's disease
* Subject with moderate to severe Crohn's disease at baseline, as defined by CDAI \> 150,
* Subject accepting to undergo two capsules endoscopy and Ileocolonoscopy procedures
* Proven patency by Agile capsule or another approach deemed clinically acceptable by the investigator, e.g. CT enterography or MRI enterography, performed within the 6 months prior to enrollment

Exclusion Criteria:

* Known gastrointestinal obstruction or strictures based on the clinical picture or pre procedure testing and profile
* Cardiac pacemakers or other implanted electromedical devices
* Swallowing disorders.
* Subject with known slow gastric emptying
* Contraindications to ileocolonoscopy or general anasthesia
* Subject with any condition, which precludes compliance with study and/or device instructions
* Women who are either pregnant or nursing at the time of screening, who intend to be during the study period, or are of child-bearing potential and do not practice medically acceptable methods of contraception.
* Subject suffers from life threatening conditions
* Subject currently participating in another clinical study
* Subject has taken NSAID medications less than one month before enrollment

Primary outcomes:
measure: Evaluate the agreement between capsule and ileocolonoscopy in the change of physician global assessment (PGA) as visualized in the TI in patients under treatment.
timeFrame: week 0 and after 6 at 12 months
Secondary outcomes:
measure: Lewis score
timeFrame: week 0 and after 6 at 12 months
measure: Segmental ileal and global CDEIS score
timeFrame: week 0 and after 6 at 12 months
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU Amiens
city: Caen
country: France
facility: CHU CAEN
city: Clermont-Ferrand
country: France
facility: CHU Clermont Ferrand
city: Clichy
country: France
facility: Hôpital Beaujon
city: Le Kremlin-Bicêtre
country: France
facility: CHU Kremlin Bicêtre
city: Lille
country: France
facility: Hôpital Huriez
city: Nancy
country: France
facility: Hôpital Brabois
city: Nantes
country: France
facility: Hôpital Hôtel Dieu
city: Nice
country: France
facility: Hôpital Archet 2
city: Paris
country: France
facility: Hôpital St Louis
city: Barcelona
country: Spain
facility: Hospital Clinic
Study officials:
affiliation: CHU Nantes, Service Hépato-gastro-entérologie 1, place Alexis Ricordeau 44093 Nantes Cedex 1
name: Dr Arnaud Bourreille, MD
role: PRINCIPAL_INVESTIGATOR
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