AI-enabled Endoscopic Prediction of Post-operative Recurrence in Crohn's Disease (PROSPER)

July 16, 2024 updated by: University College Cork

Endoscopic Multimodal Assessment Using Advanced Imaging Integrated AI to Predict Recurrence in pOSt-oPerativE CRohn's Disease - PROSPER Study

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Estimated)

225

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Michelle O'Riordan
  • Phone Number: +353 (0)21 4901759
  • Email: moriordan@ucc.ie

Study Locations

  • Belgium
      • Leuven, Belgium
        • Active, not recruiting
        • University of Leuven
  • Canada
      • Calgary, Canada
        • Recruiting
        • University of Calgary
        • Contact:
        • Principal Investigator:
          • Remo Panaccione, Professor
  • Germany
      • Erlangen, Germany
        • Active, not recruiting
        • University Hospital Erlangen
  • Ireland
      • Cork, Ireland
        • Active, not recruiting
        • Cork University Hospital
      • Cork, Ireland
        • Active, not recruiting
        • Mercy University Hospital
      • Dublin, Ireland
        • Recruiting
        • University College Dublin
        • Contact:
        • Principal Investigator:
          • Glen Doherty, Professor
      • Galway, Ireland
        • Active, not recruiting
        • University College Hospitals Galway
  • Israel
      • Tel Aviv, Israel
        • Recruiting
        • Rabin Medical Centre
        • Contact:
        • Principal Investigator:
          • Henit Yanai, Professor
  • Italy
      • Brescia, Italy
        • Active, not recruiting
        • ASST Spedali Civili
      • Milan, Italy
      • Milan, Italy
        • Recruiting
        • IRCCS Cà Granda Ospedale Maggiore
        • Contact:
        • Principal Investigator:
          • Gianeugenio Tontini, Professor
      • Milan, Italy
        • Active, not recruiting
        • University Vita-Salute San Raffaele
      • Naples, Italy
        • Recruiting
        • University Federico II
        • Contact:
        • Principal Investigator:
          • Fabiana Castiglione, Professor
      • Pavia, Italy
        • Recruiting
        • IRCCS San Matteo
        • Contact:
        • Principal Investigator:
          • Antonio Di Sabatino, Professor
    • Milan
      • Rozzano, Milan, Italy
        • Active, not recruiting
        • Istituto Clinico Humanitas

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

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

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Post-operative CD
Patients undergoing surgery or with a previous (within 3 months from the enrolment) surgery for CD
Procedure: Colonoscopy

The colonoscopy will be performed at 3 or 6 months after surgery according to FC:

  • In patients with FCP >=150µg/g at around 3 months after surgery, a colonoscopy will be immediately performed
  • In patients with FCP <150µg/g at around 3 months after surgery, the colonoscopy will be organized at 6 months after surgery

Colonoscopy will be performed using high definition white-light endoscopy (HD-WLE) followed by virtual chromoendoscopy (VCE). The neoterminal ileum, ileocolic anastomosis and right colon will be assessed.

A follow-up colonoscopy will be performed within 18 months after index colonoscopy, as standard of care.

Procedure: Intestinal biopsies
During index colonoscopy, at least 2 biopsies from each of the segments will be taken as standard of practice to assess inflammation in post-operative CD. Only in Irish sites, twelve biopsies - four in the area of ileocolonic anastomosis, four in the neo-terminal ileum and four in the colon just distal to the anastomosis- will be taken for research purposes, in addition to standard-of-care biopsies.
Procedure: Confocal laser endomicroscopy
pCLE with fluorescein injection will be performed during index colonoscopy, in centres where is available, to assess early alteration of the barrier function.
Procedure: Intestinal ultrasound
All patients will undergo a cross-sectional imaging test as part of their standard of care at 3 and 6 months after surgery. A follow-up IUS will be performed within 18 months after index colonoscopy, as standard of care.
Diagnostic test: Stool
Stool samples will be collected at 3 and 6 months after surgery and used for faecal calprotectin analysis. Research stool will be collected during the visit of index colonoscopy and at 12 months after index colonoscopy for metagenomics (only in Irish sites).
Diagnostic test: Blood
Blood will be collected at 3 and 6 months after surgery and used as standard of care. Research blood will be collected during the visit of index colonoscopy and at 12 months after index colonoscopy for research - i.e. proteomic, genomic, cell experiments (only in Irish sites).
Diagnostic test: Saliva
Saliva will be collected during the visit of index colonoscopy and at 12 months after surgery for research - i.e. optical spectroscopy (only in Irish site)
Other: Clinical follow-up
Patients will be followed-up at 6, 12 and 24 months after index endoscopy. Patients will be evaluated in clinic or by telephone call and the disease will be reassessed. The following scores will be repeated: Harvey Bradshaw Index (HBI) and CD Activity Index score (CDAI). Participants will give an update on their medication use.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Early post-operative endoscopic recurrence
Time Frame: 3 months or 6 months
Post surgical endoscopic recurrence will be defined as Simple Endoscopic Score for Crohn's Disease (SES-CD) > 2 and Rutgeerts score > i2a
3 months or 6 months
Early post-operative clinical recurrence
Time Frame: 3 months and 6 months

Post surgical clinical recurrence will be defined as:

  • CD Activity Index score (CDAI) >200 and a >70-point increase from baseline, or
  • development of a new or re-draining fistula or abscess, or
  • requiring steroids, endoscopic dilatation, or hospitalization
3 months and 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Post-operative clinical recurrence
Time Frame: 1 year and 2 years

Post surgical clinical recurrence will be defined as:

  • CD Activity Index score (CDAI) >200 and a >70-point increase from baseline, or
  • development of a new or re-draining fistula or abscess, or
  • requiring steroids, endoscopic dilatation, or hospitalization and
  • new surgery at 12 and 24 months after colonoscopy.
1 year and 2 years
Early post-operative histological recurrence
Time Frame: 3 months or 6 months
Post surgical histologic recurrence will be defined as Robarts histopathology index (RHI) >3 and PICaSSO Histological remission Index (PHRI) > 0
3 months or 6 months
Early post-operative IUS recurrence
Time Frame: 3 months or 6 months

Post surgical IUS recurrence will be assessed according to:

  • Anastomotic bowel wall thickness (BWT)
  • Bowel wall stratification (BWS)
  • Lesion length
  • Presence of mesenteric lymphadenopathy
  • Proliferation of inflammatory mesenteric fat (iFat).
  • Presence of free fluid within the peritoneal cavity
  • Presence of strictures
  • Presence of fistulae
  • Presence of abscesses
  • Limberg score
3 months or 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University College Cork

Collaborators

The Leona M. and Harry B. Helmsley Charitable Trust

Investigators

  • Study Chair: Marietta Iacucci, Professor, APC Microbiome Ireland, University College Cork

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2024

Primary Completion (Estimated)

October 31, 2025

Study Completion (Estimated)

May 31, 2026

Study Registration Dates

First Submitted

July 10, 2024

First Submitted That Met QC Criteria

July 10, 2024

First Posted (Actual)

July 17, 2024

Study Record Updates

Last Update Posted (Actual)

July 18, 2024

Last Update Submitted That Met QC Criteria

July 16, 2024

Last Verified

July 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • APC188

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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