Study of Tissue Repair in Inflammatory Bowel Disease Exploiting Organoid Technology

NCT ID: NCT06805890

Last Updated: 2025-08-22

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-07-24
• Study Completion Date: 2027-03-24

Brief Summary

Inflammatory Bowel Diseases (IBD) are chronic inflammations of the gastrointestinal tract. Regardless of the etiology, a common trait of IBD pathogenesis is the inflammatory damage inflicted on the intestinal mucosa and the loss of intestinal epithelial barrier integrity. Therefore, understanding the mechanisms that govern IEC's capacity to maintain barrier function and to orchestrate mucosal healing is considered a major goal in translational research. The investigators are interested in understanding how the inflammatory environment present in the intestinal mucosa, of IBD patients influences epithelial cells capacity to govern repair. The complexities of the cytokine and metabolic milieu present in IBD patients render the study of the contribution of each cytokine, metabolite, and intracellular pathway extremely complicated. Therefore, most of the processes that govern tissue regeneration are studied with the use of mouse models that recapitulate one or multiple features of IBD and allow for genetical modifications of the gene and pathway of interest. While mouse models are uniquely suited to study the complex crosstalk between the immune system, the microbiota, and the intestinal epithelia, they introduce the important problem of species-specific differences, which can hamper the translational value of mouse studies.

To overcome these shortcomings, the investigators propose to explore the influence of cytokines and metabolites in digestive organoids derived from patients and controls. Importantly, it was demonstrated that gene expression and innate immune responses are altered in primary organoids derived from patients with IBD, including altered ability to proliferate, respond to cytokines, metabolic capacity, and efficiently form organoids suggesting that major differences between patient's and control's epithelial cell biology can be faithfully replicated in this system.

Given these premises, the investigators propose the following objectives:

Primary objective:

The main objective of this study is to establish that patient's epithelial cells from inflamed mucosae have decreased ability to repair the intestinal mucosa, as compared to epithelial cells from non-inflamed regions in the same patient, or to control subject with no inflammatory digestive diseases.

The investigators will explore this question both deriving organoids from clinical samples and exposing them to pro inflammatory cytokines and metabolites in vitro, as well as by analyzing repair responses from the aforementioned clinical samples ex vivo.

Secondary objective

The secondary goals of this study are:

• To compare organoids derived from: epithelia in inflamed mucosa of IBD patients, epithelia in non-inflamed mucosa of IBD patients, and epithelia from the mucosa of non-IBD controls in their capacity to mount a repair response in response to inflammatory cytokines or luminal metabolites.

Namely the investigators will evaluate the following parameters:

• Their capacity to proliferate.
• Their ability to survive treatment with pro-inflammatory cytokines
• The activation of intracellular pathways associated with cell death.
• Their overall metabolic activity.
• The balance between stem and differentiated epithelial cell types.
• The transcriptional activation of protective pathways such as those associated with proliferation, migration, differentiation and cell survival.
• To evaluate hallmarks of tissue repair in biopsies derived from epithelia in inflamed mucosa of IBD patients, epithelia in non-inflamed mucosa of IBD patients, and epithelia from the mucosa of non-IBD controls, and to correlate them to the levels of inflammatory cytokines, luminal metabolites and overall disease severity. Namely the investigators will evaluate the following parameters:
• The abundance of proliferating cells.
• The activation of intracellular pathways associated with cell death and survival.
• Their overall metabolic activity.
• The balance between stem and differentiated epithelial cell types.
• The transcriptional activation of protective pathways such as those associated with proliferation, migration, differentiation and cell survival.

Conditions

Crohn Disease; Inflammatory Bowel Diseases (IBD); Ulcerative Colitis (Disorder)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Control group

Patients of either sex aged 18 years or older and undergoing a screening colonoscopy in the context of a family history of colonic neoplasia, follow-up of colonic polyps or functional intestinal disorders OR undergoing intestinal resection for intestinal neoplasia, occlusive syndrome or colostomy

Group Type: SHAM_COMPARATOR

Colonoscopy - biopsies in healthy tissue

Intervention Type: PROCEDURE

Collection of 10 colonic biopsies in healthy tissue

Surgical resection - healthy mucous membrane

Intervention Type: PROCEDURE

Collection of a portion of healthy mucous membrane

IBD group

Patients of either sex aged 18 years or older with Crohn's Disease or ulcerative colitis in accordance with accepted clinical, endoscopic, histological and/or radiologic criteria, regardless of the level, severity of the disease or duration of disease progression or patients undergoing a screening colonoscopy in the context of IBD disease follow-up OR undergoing intestinal resection for IBD disease aggravation

Group Type: EXPERIMENTAL

Colonoscopy - IBD inflamed tissue

Intervention Type: PROCEDURE

Collection of 10 colonic biopsies in IBD inflamed tissue

Surgical resection - IBD inflamed mucous membrane

Intervention Type: PROCEDURE

Collection of a portion of IBD inflamed mucous membrane

Surgical resection - healthy mucous membrane

Intervention Type: PROCEDURE

Collection of a portion of healthy mucous membrane

Interventions

Colonoscopy - IBD inflamed tissue

Collection of 10 colonic biopsies in IBD inflamed tissue

Intervention Type: PROCEDURE

Surgical resection - IBD inflamed mucous membrane

Collection of a portion of IBD inflamed mucous membrane

Intervention Type: PROCEDURE

Colonoscopy - biopsies in healthy tissue

Collection of 10 colonic biopsies in healthy tissue

Intervention Type: PROCEDURE

Surgical resection - healthy mucous membrane

Collection of a portion of healthy mucous membrane

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Patients of either sex aged 18 years or older
• Patient that have read the information form and signed consent
• Patient covered with health insurance
• Patients with Crohn's Disease or ulcerative colitis in accordance with accepted clinical, endoscopic, histological and/or radiologic criteria, regardless of the level, severity of the disease or duration of disease progression.
• Patients with colonic involvement of Crohn's disease or ulcerative colitis
• Patients undergoing a screening colonoscopy in the context of IBD disease follow-up OR undergoing intestinal resection for IBD disease aggravation

• Patients of either sex aged 18 years or older
• Patient that have read the information form and signed consent
• Patient covered with health insurance
• Patients undergoing a screening colonoscopy in the context of a family history of colonic neoplasia, follow-up of colonic polyps or functional intestinal disorders OR undergoing intestinal resection for intestinal neoplasia, occlusive syndrome or colostomy

• Contraindication to the anaesthetic or colonoscopy procedure
• Patients without colonic involvement of Crohn's disease or ulcerative colitis
• Patients of Adults without legal capacity
• Patients in Health and Social Establishments
• Persons in emergency situations
• Persons deprived of their liberty
• Non-affiliated to a social security scheme
• Absence or refusal of the informed consent

• IBD disease revealed during colonoscopy or gastrointestinal resection
• Patient suffering from Immune-Mediated Inflammatory Diseases (IMIDs)
• Contraindication to the anaesthetic or colonoscopy procedure
• Patients of Adults without legal capacity
• Patients in Health and Social Establishments
• Persons in emergency situations
• Persons deprived of their liberty
• Non-affiliated to a social security scheme
• Absence or refusal of the informed consent

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique Hopitaux De Marseille

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Nord Hospital

Marseille, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Lucas GUILLO

Role: CONTACT

promotion.interne@ap-hm.fr

0491335817 ext. +33

Facility Contacts

Lucas GUILLO

Role: primary

promotion.interne@ap-hm.fr

0491335817 ext. +33

Other Identifiers

2024-A00510-47

Identifier Type: OTHER

Identifier Source: secondary_id

RCAPHM24_0062

Identifier Type: -

Identifier Source: org_study_id