Preclinical Evaluation of Multimodal Therapeutic Strategies in Intestinal Irradiation and Inflammatory Bowel Disease From Organoids (INTRUST)

This study is carried out in patients with IBD and healthy subjects requiring ileocolonoscopy as part of routine care (disease monitoring or polyp/colon cancer screening). It aims the generation and culturing of organoids from digestive biopsies recovered from healthy and/or pathological (inflammatory) ileal and/or colonic mucosa during an ileo-colonoscopy. These cultures will make it possible to validate the organoid production method used in the context of the research (primary objective). In a second phase (secondary objectives), the study will aim to setup a screening tool by irradiating the organoids (step one) and then evaluate in vitro the regenerative activity of treatments dedicated to improve inflammatory bowel diseases and acute radiation enteritis (step two).

Study Overview

• Status: Recruiting
• Conditions: Inflammatory Bowel Diseases; Radiation Enteritis
• Intervention / Treatment: Other: biopsy

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Hauts-de-Seine
    • Neuilly-sur-Seine, Hauts-de-Seine, France, 92200
      • Recruiting
      • Groupe Hospitalier Ambroise Paré Hartmann
      • Contact: Xavier Treton, MD, PhD; Phone Number: +33146413178; Email: xavier.treton@institutdesmici.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

- Group 1: active IBD

• 18 years old or older
• Assured IBD diagnosis (Crohn's disease/ulcerative colitis) according to European Crohn's and Colitis Organisation (ECCO) 2019 consensus criteria
• Active IBD (Harvey-Bradshaw score of 4 or above for Crohn's disease or partial Mayo score of 3 or above for ulcerative colitis)
• Indication to perform a coloscopy
• Written consent for study participation obtained

Or

- Group 2: inactive IBD

• 18 years old or older
• Assured IBD diagnosis (Crohn's disease/ulcerative colitis) according to ECCO 2019 consensus criteria
• Inactive IBD (Harvey-Bradshaw score below 4 for Crohn's disease or partial Mayo score below 3 for ulcerative colitis)
• Indication to perform a coloscopy
• Written consent for study participation obtained

Or

- Group 3: Control

• 18 years old or older
• Indication to perform a coloscopy to detect polyp
• No known bowel disease
• Written consent for study participation obtained

Exclusion Criteria:

• Inability to understand, read, sign informed consent and/or express consent
• Person subject to legal protection (curator, guardianship or safeguard of justice),
• Deprivation of liberty by judicial or administrative decision,
• Non-affiliation to a social security scheme or non-beneficiary of such a scheme
• Pregnant, parturient, breastfeeding women
• Contraindication to performing biopsies
• Participation in other therapeutic research that may modify the behavior of intestinal cells (for example, drug research for the treatment of IBD)
• Anticoagulant treatment or bleeding disorder
• Person subject to a judicial safeguard measure
• People hospitalized without consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IBD; active or quiescent	Other: biopsy; endoscopy biopsies (6)
Active Comparator: control; polyp screening	Other: biopsy; endoscopy biopsies (6)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Validation of organoid-production method - quantity	Quantity of organoids created	Day 1
Validation of organoid-production method - size	Size of organoids created	Day 1
Validation of organoid-production method - cell growth	Cell-growth kinetics	Day 1
Validation of organoid-production method - cell composition	Cell composition assessed by immunofluorescence	Day 1
Validation of organoid-production method - cell composition	Cell composition compared to native-biopsy cell composition assessed by single-cell RNA sequencing	Day 1
Validation of organoid-production method - cell apoptosis	Cell-apoptosis level assessed by immunofluorescence	Day 1
Validation of organoid-production method - tight junctions	Number of tight junctions between cells assessed by immunofluorescence	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Screening-tool setup - quantity	Quantity of organoids after irradiation	Day 1
Screening-tool setup - size	Size of organoids after irradiation	Day 1
Screening-tool setup - cell growth	Cell-growth kinetics after irradiation	Day 1
Screening-tool setup - cell composition	Cell composition after irradiation assessed by immunofluorescence	Day 1
Screening-tool setup - cell apoptosis	Cell-apoptosis level after irradiation assessed by immunofluorescence	Day 1
Screening-tool setup - tight junctions	Number of tight junctions between cells after irradiation assessed by immunofluorescence	Day 1
Screening-tool setup - inflammatory cytokines	Level of inflammatory-cytokines produced after irradiation assessed by single-cell RNA sequencing	Day 1
In-vitro treatment evaluation - quantity	Quantity of organoids after irradiation and in presence of treatment	Day 1
In-vitro treatment evaluation - size	Size of organoids after irradiation and in presence of treatment	Day 1
In-vitro treatment evaluation - cell growth	Cell-growth kinetics after irradiation and in presence of treatment	Day 1
In-vitro treatment evaluation - cell composition	Cell composition after irradiation and in presence of treatment assessed by immunofluorescence	Day 1
In-vitro treatment evaluation - cell composition	Cell composition compared to native-biopsy cell composition assessed by single-cell RNA sequencing	Day 1
In-vitro treatment evaluation - cell apoptosis	Cell-apoptosis level after irradiation and in presence of treatment assessed by immunofluorescence	Day 1
In-vitro treatment evaluation - tight junction	Number of tight junctions between cells after irradiation and in presence of treatment assessed by immunofluorescence	Day 1
In-vitro treatment evaluation - inflammatory cytokines	Level of inflammatory-cytokines produced after irradiation and in presence of treatment assessed by single-cell RNA sequencing	Day 1

Collaborators and Investigators

• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France
• Collaborators: National Research Agency, France

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2022
• Primary Completion (Estimated): September 18, 2025
• Study Completion (Estimated): September 18, 2025

Study Registration Dates

• First Submitted: June 10, 2022
• First Submitted That Met QC Criteria: June 15, 2022
• First Posted (Actual): June 21, 2022

Study Record Updates

• Last Update Posted (Actual): June 22, 2023
• Last Update Submitted That Met QC Criteria: June 21, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: colonoscopy
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Intestinal Diseases; Enteritis
• Other Study ID Numbers: C20-53; 2021-A02973-38 (Registry Identifier: IDRCB)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No