Clinical trial NCT06362174: Capsule & Omics for pRedicting Exacerbation of Crohn's Disease
Official title: Capsule & Omics for pRedicting Exacerbation of Crohn's Disease (CORE-CD)
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Crohn's Disease
Lead sponsor: Sheba Medical Center
Sponsor class: OTHER_GOV
First posted: 2024-04-12
Enrollment: 62
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Eligible patients will consist of adult CD patients \>16YO in clinical remission, as determined by the validated Crohn's disease activity index (CDAI) of \<150 and whose disease is known to involve the small bowel as either small bowel CD or ileo-colonic CD. Patients will have to be in steroid-free remission, whether induced medically or surgically, for at least 3 months before inclusion. Patients will be included regardless of the medication used for their treatment, but the dose of medication will be required to be stable before enrollment (60 days for thiopurines, Methotrexate, infliximab, vedolizumab, adalimumab and ustekinumab, 30 days for all other agents).

Brief summary: The research group have previously evaluated the benefit of serial consecutive capsule endoscopy as monitoring tool for Crohn's disease in remission, demonstrating its superior accuracy for disclosing inflammation and for prediction of flares in comparison to other diagnostic modalities such as magnetic resonance enterography and inflammatory biomarkers. Subsequently, deep learning algorithms had developed to provide excellent accuracy for identification and grading of ulcers and intestinal strictures on capsule endoscopy still images. The investigators will advance this knowledge using a parallel two-parts approach.

Detailed description: Part I - A retrospective study will use stored capsule and clinical datasets from 120 previously enrolled CD patients in remission, who underwent capsule based 24-months monitoring as part of two prior similar research projects (60 in each of the Israeli Inflammatory bowel disease Research Nucleus (IIRN), IIRN-I and IIRN-II-CURE- projects), aiming to predict and prevent flares based on capsule studies. The investigators will now utilize the accumulated visual data to develop AI-based complete film readouts and integrate the resultant visual omics data with previously derived microbiome and biomarker data, to serve as a discovery cohort for machine learning models predicting clinical exacerbation in patients in remission, which was witnessed in 27% of IIRN-I cohort within the 24m study.

Part II - A prospective observational study will enroll a new IIRN-III cohort of 60 (+6 attrition-considered) Crohn's Disease patients\>16 years old in clinical remission. The investigators will deliberately use similar inclusion, monitoring design and outcome definitions as IIRN-I \& II studies, to allow cross-cohort comparative validity. Procedures will include baseline colonoscopy, pan-enteric capsule and magnetic resonance enterography/Intestinal ultrasound, and thereafter serial capsule studies or every 6 months for 24 months. Newly acquired Omics will include baseline mucosal +colonic wash transcriptomics obtained during the baseline colonoscopy, serial dense stool microbiome and blood metabolomics, and a computerized frequency questionnaire, diet omics data. A densely sampled 24 months stool will be used to develop novel multi-omics tools predicting flares. The investigators will also use the datasets to explore the mechanisms and pathways involved in triggering remission transition into a clinical flare.

Follow- up can optionally extend to 36 months.

Eligibility criteria: Inclusion Criteria:

* Age above 16
* Established Crohn's disease (CD) for at least 3 months
* Steroid free remission whether induced medically or surgically, for at least 3 months before inclusion
* CDAI\<150
* Stable dose before enrollment:

  60 days for thiopurines, Methotrexate, Infliximab and Vedolizumab; 30 days for all other agents.

Exclusion Criteria:

* Corticosteroid use within the last 3 months
* Severe co-morbidities: liver, kidney, neurologic, metabolic or cardio-respiratory disorders not controlled at the time of enrollment
* Difficulty swallowing / history of aspirations or dysphagia
* Implanted metal objects precluding performance of MRI
* Cardiac pace-maker
* Known or suspected intestinal obstruction/stricture
* Pregnancy
* Alcohol / drug dependency
* Use of NSAIDs (including aspirin) for more than 3 continuous days, or during the 4 weeks preceding baseline visit.

Primary outcomes:
measure: Crohn's Disease Activity Index score (CDAI)
timeFrame: Score will be calculated every 3 months assessed up to 36 months. If score above 150 and a rise above 70 points from baseline patient will be withdrawn with clinical flare
measure: Disease related complications
timeFrame: During hospitalization or after evaluation of tests results every 3 months, assessed up to 36 months
measure: disease related hospitalization
timeFrame: During hospitalization or after evaluation of tests results every 3 months, assessed up to 36 months.
measure: Change of crohn's disease medications
timeFrame: Every 3 months, assessed up to 36 months.
measure: opinion of the principle investigator (PI) or the treating physician
timeFrame: Every 3 months, assessed up to 36 months.
Secondary outcomes:
measure: The rate of clinical flare accompanied by objective signs of mucosal inflammation.
timeFrame: through study completion, an average of 2 years.
measure: The rate of inflammatory worsening with/without accompanying clinical symptoms
timeFrame: through study completion, an average of 2 years.
Other outcomes:
Locations:
city: Tel-Hashomer
country: Israel
facility: Sheba Medical Center
Study officials:
affiliation: Sheba Medical Center
name: Shomron Ben- Horin, PhD
role: PRINCIPAL_INVESTIGATOR
References: