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

Study Overview
=================
Brief 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).

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

Conditions
-----------------
Radiation Enteritis, Inflammatory Bowel Diseases

Intervention / Treatment
-----------------
* Other: biopsy


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IBD<br>active or quiescent | Other: biopsy<br>* endoscopy biopsies (6)<br>|
| Active Comparator: control<br>polyp screening | Other: biopsy<br>* endoscopy biopsies (6)<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
colonoscopy