Clinical trial NCT06505304: AI-enabled Endoscopic Prediction of Post-operative Recurrence in Crohn's Disease
Official title: Endoscopic Multimodal Assessment Using Advanced Imaging Integrated AI to Predict Recurrence in pOSt-oPerativE CRohn's Disease - PROSPER Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Crohn Disease
Keywords: Crohn's disease
Artificial Intelligence
Virtual Chromoendoscopy
Confocal laser endomicroscopy
OMIC
Machine Learning
Post-operative recurrence
Lead sponsor: University College Cork
Sponsor class: OTHER
Collaborators: name: The Leona M. and Harry B. Helmsley Charitable Trust
First posted: 2024-07-17
Enrollment: 225
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Males and females aged between 18 and 75 years old and with an established diagnosis of CD, who have undergone surgery no more than three months before study entry, or have surgery planned, will be consecutively recruited after obtaining written consent. The sample size for the study is 225

Brief summary: This is a multicentre prospective international observational study. This study aims to introduce a novel multidimensional approach to precision imaging, enabling the identification and stratification of high-risk patients who can potentially benefit from early treatments to halt the progression of Crohn's disease (CD). The investigators will develop a novel endoscopic assessment system using endoscopic enhanced imaging (EEI) to evaluate early post-surgical changes and predict post-operative CD recurrence (POCr). By integrating with immune marker profiling, clinical data, and AI assessment of EEI and histology, the investigators further plan to improve risk stratification and reduce interobserver variability.

Detailed description: Background:

Up to 70% of Crohn's disease (CD) patients will undergo a surgical resection in their lifetime. However, surgery is non-curative since 50% of patients have a recurrence, and about one-third need repeat surgery. The tools currently used to assess CD recurrences, such as faecal calprotectin (FCP), cross-sectional imaging (small bowel ultrasound, MRI scan) and conventional endoscopy, have a limited role in predicting early Post-Operative CD recurrence (POCr). Distinguishing inflammatory disease recurrence from post-surgical ischemic or suture-related alterations poses a significant challenge. Endoscopic Enhanced imaging (EEI) techniques like virtual electronic chromoendoscopy (VCE) and biopsy-like probe-based confocal laser endomicroscopy (pCLE) combined with artificial intelligence, can improve the detection of mucosal/vascular changes before major alterations become evident. VCE is available simply by switching a button. The pCLE probe will be passed through the endoscope channel like a biopsy forceps, enabling real-time, histology-like images of the intestine's lining and the gut barrier.

Study summary:

This is a multicentre prospective international observational study. This study aims to introduce a novel multidimensional approach to precision imaging, enabling the identification and stratification of high-risk patients who can potentially benefit from early treatments to halt the progression of CD.

The investigators will develop a novel endoscopic assessment system using EEI to evaluate early post-surgical changes and predict POCr. By integrating with immune marker profiling, clinical data, and AI assessment of EEI and histology, the investigators further plan to improve risk stratification and reduce interobserver variability. A detailed exploratory analysis will only be done in a cohort of patients in Ireland. The correlation between the new scoring system and established endoscopic and histologic scores, cross-sectional imaging, and non-invasive markers of inflammation will be evaluated. A multimodal machine learning model will be developed on EEI videos, histology, clinical data and immune molecular analysis to stratify patients' risk of early recurrence and long-term outcomes. The study will be divided into three phases:

* In the first phase, descriptor criteria for the assessment of post-operative Crohn's Disease will be defined. Gastroenterologists experienced in IBD endoscopy will review images and videos from an existing library showing the different grade of inflammation of the modified Rutgeerts score. These will be used for a stepwise discussion. A round table discussion using modified Delphi method will be conducted to ensure equal participation and identify the best component descriptors of endoscopic recurrence of CD. The components that achieved 100% consensus will be selected and the most important endoscopy predictive variables will be confirmed by using a machine learning technique. Finally, a new endoscopic score will be generated. Further, the investigators will first validate the new endoscopic score using the first 30 consecutive VCE and pCLE videos of POCr patients recruited in the multicenter PROSPER study. A structured consensus will be conducted with experts in Inflammatory Bowel Disease, endoscopy and histology to define the endoscopic findings of mucosal, vascular and intestinal barrier function. Subsequently, the investigators will prospectively validate the score in a large cohort of POCr patients enrolled in the PROSPER study and assess the diagnostic accuracy of the new scoring system in predicting post-surgical recurrence. Clinical information, blood, saliva, stool, and bowel specimens will be taken. Cross-sectional imaging (magnetic resonance imaging -MRI-, intestinal ultrasound -IUS-), endoscopy VCE and pCLE (in equipped centres) will be performed according to stool calprotectin 3 months after surgery. Patients will be followed up for 24 months and the results of the follow-up colonoscopy performed, as standard of care, within 18 months from the index colonoscopy, will be collected.
* In the second phase, the investigators will externally validate and reproduce the new scoring system by gastroenterologists using a computerized training module.
* In the third phase, an advanced computer-aided quantitative analysis of videos, images from VCE and pCLE, and digital histology will be developed and validated to enhance the prediction of POCr. Additionally, further machine learning models will be developed, utilizing comprehensive data from blood, stool, cross-sectional imaging, endoscopy, histology, immune markers, and OMICs to predict POCr and long-term outcomes.

Eligibility criteria: Inclusion Criteria:

* Patients aged between 18 years and 75 years.
* Established diagnosis of CD at least six months prior to study.
* Patients who have undergone intestinal resection within 3 months before study entry or have surgery planned.

Exclusion Criteria:

* Inability to provide consent.
* Presence of serious co-morbidities (clinical contraindication).
* Presence of ostomy.
* Pregnancy or breastfeeding.
* Contraindication for colonoscopy or biopsies.
* Boston Bowel Preparation Scale Score \<2 in the rectum plus left-sided colon.

Exclusion criteria for pCLE only:

* Allergy to nuts or shellfish.
* Severe or uncontrolled asthma.
* Use of beta blockers.
* Previous history of reaction to fluorescein.

Patients excluded from pCLE can still enter the study and undergo only standard-of-care endoscopy.

Primary outcomes:
measure: Early post-operative endoscopic recurrence
timeFrame: 3 months or 6 months
measure: Early post-operative clinical recurrence
timeFrame: 3 months and 6 months
Secondary outcomes:
measure: Post-operative clinical recurrence
timeFrame: 1 year and 2 years
measure: Early post-operative histological recurrence
timeFrame: 3 months or 6 months
measure: Early post-operative IUS recurrence
timeFrame: 3 months or 6 months
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: University of Leuven
city: Calgary
country: Canada
facility: University of Calgary
city: Erlangen
country: Germany
facility: University Hospital Erlangen
city: Cork
country: Ireland
facility: Cork University Hospital
city: Cork
country: Ireland
facility: Mercy University Hospital
city: Dublin
country: Ireland
facility: University College Dublin
city: Galway
country: Ireland
facility: University College Hospitals Galway
city: Tel Aviv
country: Israel
facility: Rabin Medical Centre
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: Milan
city: Brescia
country: Italy
facility: ASST Spedali Civili
city: Milan
country: Italy
facility: ASST Fatebenefratelli Sacco
city: Milan
country: Italy
facility: IRCCS Cà Granda Ospedale Maggiore
city: Milan
country: Italy
facility: University Vita-Salute San Raffaele
city: Naples
country: Italy
facility: University Federico II
city: Pavia
country: Italy
facility: IRCCS San Matteo
Study officials:
affiliation: APC Microbiome Ireland, University College Cork
name: Marietta Iacucci, Professor
role: STUDY_CHAIR
References:
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citation: Gionchetti P, Dignass A, Danese S, Magro Dias FJ, Rogler G, Lakatos PL, Adamina M, Ardizzone S, Buskens CJ, Sebastian S, Laureti S, Sampietro GM, Vucelic B, van der Woude CJ, Barreiro-de Acosta M, Maaser C, Portela F, Vavricka SR, Gomollon F; ECCO. 3rd European Evidence-based Consensus on the Diagnosis and Management of Crohn's Disease 2016: Part 2: Surgical Management and Special Situations. J Crohns Colitis. 2017 Feb;11(2):135-149. doi: 10.1093/ecco-jcc/jjw169. Epub 2016 Sep 22.
citation: Iacucci M, Ghosh S, Daperno M. Post-operative Recurrence of Crohn's Disease: There Is More to It than Meets the Eye. J Crohns Colitis. 2016 Sep;10(9):999-1000. doi: 10.1093/ecco-jcc/jjw094. Epub 2016 May 4. No abstract available.
citation: Riviere P, Vermeire S, Irles-Depe M, Van Assche G, Rutgeerts P, de Buck van Overstraeten A, Denost Q, Wolthuis A, D'Hoore A, Laharie D, Ferrante M. No Change in Determining Crohn's Disease Recurrence or Need for Endoscopic or Surgical Intervention With Modification of the Rutgeerts' Scoring System. Clin Gastroenterol Hepatol. 2019 Jul;17(8):1643-1645. doi: 10.1016/j.cgh.2018.09.047. Epub 2018 Oct 4.
citation: Auzoux J, Boschetti G, Anon B, Aubourg A, Caulet M, Poisson L, Besson P, Lecomte T, Roger S, Picon L, Nancey S, Moussata D, Flourie B. Usefulness of confocal laser endomicroscopy for predicting postoperative recurrence in patients with Crohn's disease: a pilot study. Gastrointest Endosc. 2019 Jul;90(1):151-157. doi: 10.1016/j.gie.2019.02.030. Epub 2019 Mar 5.
citation: Rispo A, Imperatore N, Testa A, Nardone OM, Luglio G, Caporaso N, Castiglione F. Diagnostic Accuracy of Ultrasonography in the Detection of Postsurgical Recurrence in Crohn's Disease: A Systematic Review with Meta-analysis. Inflamm Bowel Dis. 2018 Apr 23;24(5):977-988. doi: 10.1093/ibd/izy012.
citation: Iacucci M, Cannatelli R, Parigi TL, Nardone OM, Tontini GE, Labarile N, Buda A, Rimondi A, Bazarova A, Bisschops R, Del Amor R, Meseguer P, Naranjo V, Ghosh S, Grisan E; PICaSSO group. A virtual chromoendoscopy artificial intelligence system to detect endoscopic and histologic activity/remission and predict clinical outcomes in ulcerative colitis. Endoscopy. 2023 Apr;55(4):332-341. doi: 10.1055/a-1960-3645. Epub 2022 Oct 13.