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

Inflammatory Bowel Diseases Clinical Trial

— INTRUST  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05425901
• Other study ID #: C20-53
• Secondary ID: 2021-A02973-38
• Status: Recruiting
• Phase: N/A
• Start date: September 19, 2022
• Est. completion date: September 18, 2025

Study information

• Verified date: June 2023
• Source: Institut National de la Santé Et de la Recherche Médicale, France
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: September 18, 2025
• Est. primary completion date: September 18, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Enteritis
• Inflammatory Bowel Diseases
• Intestinal Diseases
• Radiation Enteritis

Intervention

Other:
• biopsy
endoscopy biopsies (6)

Locations

Country	Name	City	State
France	Groupe Hospitalier Ambroise Paré Hartmann	Neuilly-sur-Seine	Hauts-de-Seine

Sponsors (2)

Lead Sponsor	Collaborator
Institut National de la Santé Et de la Recherche Médicale, France	National Research Agency, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Validation of organoid-production method - quantity	Quantity of organoids created	Day 1
Primary	Validation of organoid-production method - size	Size of organoids created	Day 1
Primary	Validation of organoid-production method - cell growth	Cell-growth kinetics	Day 1
Primary	Validation of organoid-production method - cell composition	Cell composition assessed by immunofluorescence	Day 1
Primary	Validation of organoid-production method - cell composition	Cell composition compared to native-biopsy cell composition assessed by single-cell RNA sequencing	Day 1
Primary	Validation of organoid-production method - cell apoptosis	Cell-apoptosis level assessed by immunofluorescence	Day 1
Primary	Validation of organoid-production method - tight junctions	Number of tight junctions between cells assessed by immunofluorescence	Day 1
Secondary	Screening-tool setup - quantity	Quantity of organoids after irradiation	Day 1
Secondary	Screening-tool setup - size	Size of organoids after irradiation	Day 1
Secondary	Screening-tool setup - cell growth	Cell-growth kinetics after irradiation	Day 1
Secondary	Screening-tool setup - cell composition	Cell composition after irradiation assessed by immunofluorescence	Day 1
Secondary	Screening-tool setup - cell apoptosis	Cell-apoptosis level after irradiation assessed by immunofluorescence	Day 1
Secondary	Screening-tool setup - tight junctions	Number of tight junctions between cells after irradiation assessed by immunofluorescence	Day 1
Secondary	Screening-tool setup - inflammatory cytokines	Level of inflammatory-cytokines produced after irradiation assessed by single-cell RNA sequencing	Day 1
Secondary	In-vitro treatment evaluation - quantity	Quantity of organoids after irradiation and in presence of treatment	Day 1
Secondary	In-vitro treatment evaluation - size	Size of organoids after irradiation and in presence of treatment	Day 1
Secondary	In-vitro treatment evaluation - cell growth	Cell-growth kinetics after irradiation and in presence of treatment	Day 1
Secondary	In-vitro treatment evaluation - cell composition	Cell composition after irradiation and in presence of treatment assessed by immunofluorescence	Day 1
Secondary	In-vitro treatment evaluation - cell composition	Cell composition compared to native-biopsy cell composition assessed by single-cell RNA sequencing	Day 1
Secondary	In-vitro treatment evaluation - cell apoptosis	Cell-apoptosis level after irradiation and in presence of treatment assessed by immunofluorescence	Day 1
Secondary	In-vitro treatment evaluation - tight junction	Number of tight junctions between cells after irradiation and in presence of treatment assessed by immunofluorescence	Day 1
Secondary	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