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

• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05425901
• Collaborator: National Research Agency, France (Other)
• Enrollment: 80
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 43.1
• Patients Per Site Per Month: 1.9

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Radiation Enteritis; Inflammatory Bowel Diseases	Other: biopsy	N/A

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 80 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Preclinical Evaluation of Multimodal Therapeutic Strategies in Intestinal Irradiation and Inflammatory Bowel Disease From Organoids
• Anticipated Study Start Date: Jun 29, 2022
• Anticipated Primary Completion Date: Jun 29, 2025
• Anticipated Study Completion Date: Jan 31, 2026

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Validation of organoid-production method - quantity [Day 1]

   Quantity of organoids created

2. Validation of organoid-production method - size [Day 1]

   Size of organoids created

3. Validation of organoid-production method - cell growth [Day 1]

   Cell-growth kinetics

4. Validation of organoid-production method - cell composition [Day 1]

   Cell composition assessed by immunofluorescence

5. Validation of organoid-production method - cell composition [Day 1]

   Cell composition compared to native-biopsy cell composition assessed by single-cell RNA sequencing

6. Validation of organoid-production method - cell apoptosis [Day 1]

   Cell-apoptosis level assessed by immunofluorescence

7. Validation of organoid-production method - tight junctions [Day 1]

   Number of tight junctions between cells assessed by immunofluorescence

Secondary Outcome Measures

1. Screening-tool setup - quantity [Day 1]

   Quantity of organoids after irradiation

2. Screening-tool setup - size [Day 1]

   Size of organoids after irradiation

3. Screening-tool setup - cell growth [Day 1]

   Cell-growth kinetics after irradiation

4. Screening-tool setup - cell composition [Day 1]

   Cell composition after irradiation assessed by immunofluorescence

5. Screening-tool setup - cell apoptosis [Day 1]

   Cell-apoptosis level after irradiation assessed by immunofluorescence

6. Screening-tool setup - tight junctions [Day 1]

   Number of tight junctions between cells after irradiation assessed by immunofluorescence

7. Screening-tool setup - inflammatory cytokines [Day 1]

   Level of inflammatory-cytokines produced after irradiation assessed by single-cell RNA sequencing

8. In-vitro treatment evaluation - quantity [Day 1]

   Quantity of organoids after irradiation and in presence of treatment

9. In-vitro treatment evaluation - size [Day 1]

   Size of organoids after irradiation and in presence of treatment

10. In-vitro treatment evaluation - cell growth [Day 1]

    Cell-growth kinetics after irradiation and in presence of treatment

11. In-vitro treatment evaluation - cell composition [Day 1]

    Cell composition after irradiation and in presence of treatment assessed by immunofluorescence

12. In-vitro treatment evaluation - cell composition [Day 1]

    Cell composition compared to native-biopsy cell composition assessed by single-cell RNA sequencing

13. In-vitro treatment evaluation - cell apoptosis [Day 1]

    Cell-apoptosis level after irradiation and in presence of treatment assessed by immunofluorescence

14. In-vitro treatment evaluation - tight junction [Day 1]

    Number of tight junctions between cells after irradiation and in presence of treatment assessed by immunofluorescence

15. In-vitro treatment evaluation - inflammatory cytokines [Day 1]

    Level of inflammatory-cytokines produced after irradiation and in presence of treatment assessed by single-cell RNA sequencing

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hopital Beaujon	Clichy	Hauts De Seine	France	92120

Sponsors and Collaborators

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

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Institut National de la Santé Et de la Recherche Médicale, France
• ClinicalTrials.gov Identifier: NCT05425901
• Other Study ID Numbers: C20-53; 2021-A02973-38
• First Posted: Jun 21, 2022
• Last Update Posted: Jun 21, 2022
• Last Verified: Jun 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Institut National de la Santé Et de la Recherche Médicale, France: colonoscopy
• Additional relevant MeSH terms: Intestinal Diseases; Inflammatory Bowel Diseases; Enteritis

Study Results

No Results Posted as of Jun 21, 2022