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

NCT ID: NCT06505304

Last Updated: 2024-07-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

225 participants

Study Classification

OBSERVATIONAL

Study Start Date

2024-05-01

Study Completion Date

2026-05-31

Brief Summary

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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

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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.

Conditions

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Crohn Disease

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Post-operative CD

Patients undergoing surgery or with a previous (within 3 months from the enrolment) surgery for CD

Colonoscopy

Intervention Type PROCEDURE

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.

Intestinal biopsies

Intervention Type PROCEDURE

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.

Confocal laser endomicroscopy

Intervention Type PROCEDURE

pCLE with fluorescein injection will be performed during index colonoscopy, in centres where is available, to assess early alteration of the barrier function.

Intestinal ultrasound

Intervention Type PROCEDURE

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.

Stool

Intervention Type DIAGNOSTIC_TEST

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).

Blood

Intervention Type DIAGNOSTIC_TEST

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).

Saliva

Intervention Type DIAGNOSTIC_TEST

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)

Clinical follow-up

Intervention Type OTHER

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.

Interventions

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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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type PROCEDURE

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).

Intervention Type 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).

Intervention Type 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)

Intervention Type DIAGNOSTIC_TEST

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.

Intervention Type OTHER

Eligibility Criteria

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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.


* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The Leona M. and Harry B. Helmsley Charitable Trust

OTHER

Sponsor Role collaborator

University College Cork

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Marietta Iacucci, Professor

Role: STUDY_CHAIR

APC Microbiome Ireland, University College Cork

Locations

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University of Leuven

Leuven, , Belgium

Site Status ACTIVE_NOT_RECRUITING

University of Calgary

Calgary, , Canada

Site Status RECRUITING

University Hospital Erlangen

Erlangen, , Germany

Site Status ACTIVE_NOT_RECRUITING

Cork University Hospital

Cork, , Ireland

Site Status ACTIVE_NOT_RECRUITING

Mercy University Hospital

Cork, , Ireland

Site Status ACTIVE_NOT_RECRUITING

University College Dublin

Dublin, , Ireland

Site Status RECRUITING

University College Hospitals Galway

Galway, , Ireland

Site Status ACTIVE_NOT_RECRUITING

Rabin Medical Centre

Tel Aviv, , Israel

Site Status RECRUITING

Istituto Clinico Humanitas

Rozzano, Milan, Italy

Site Status ACTIVE_NOT_RECRUITING

ASST Spedali Civili

Brescia, , Italy

Site Status ACTIVE_NOT_RECRUITING

ASST Fatebenefratelli Sacco

Milan, , Italy

Site Status RECRUITING

IRCCS Cà Granda Ospedale Maggiore

Milan, , Italy

Site Status RECRUITING

University Vita-Salute San Raffaele

Milan, , Italy

Site Status ACTIVE_NOT_RECRUITING

University Federico II

Naples, , Italy

Site Status RECRUITING

IRCCS San Matteo

Pavia, , Italy

Site Status RECRUITING

Countries

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Belgium Canada Germany Ireland Israel Italy

Central Contacts

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Michelle O'Riordan

Role: CONTACT

+353 (0)21 4901759

Facility Contacts

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Cathy Liu

Role: primary

Janet Rebollos

Role: primary

Shaked Cohen

Role: primary

Rosanna Cannatelli

Role: primary

Gianeugenio Tontini, Professor

Role: primary

Olga Maria Nardone, Dr

Role: primary

Mariangela Delliponti

Role: primary

References

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Rutgeerts P, Geboes K, Vantrappen G, Beyls J, Kerremans R, Hiele M. Predictability of the postoperative course of Crohn's disease. Gastroenterology. 1990 Oct;99(4):956-63. doi: 10.1016/0016-5085(90)90613-6.

Reference Type BACKGROUND
PMID: 2394349 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27660342 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27147451 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30291910 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30849396 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29688470 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 36228649 (View on PubMed)

Other Identifiers

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APC188

Identifier Type: -

Identifier Source: org_study_id

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