Intestinal Stem Cells Characterization

Not Applicable

Completed

• Conditions: Inflammatory Bowel Diseases
• Interventions: Procedure: Endoscopic biopsies

• Registration Number: NCT02874365
• Lead Sponsor: University Hospital, Toulouse

Brief Summary

A monocentric pilot studying intestinal organoids from endoscopic biopsies of IBD (Crohn and ulcerative colitis), FAP patients and healthy controls. Investigate the morphological characteristics of organoids, the expression of genes and proteins of the Wnt/APC/beta-catenin pathway within both ISC.

Detailed Description

Intestinal organoids are 3D mini-guts produced in vitro based on intestinal stem cell (ISC) capabilities. These organoids contain all of the intestinal epithelial cells. The renewal of the two kinds of ISCs, which are present at the bottom of intestinal crypts, is controlled by Wnt/APC/beta-catenin pathway. Mutations of genes involved in this pathway are found in intestinal polyposes like familial adenomatous polyposis (FAP, APC gene).

This model is of interest to study early pathophysiological events occurring within intestinal epithelium, in the context of FAP and inflammatory bowel diseases (IBD). An excessive proliferation or an abnormal healing is found in FAP and IBD respectively. Investigators hypothesized that it could specifically involved one of the 2 ISCs. Columnar basal cells (CBC) and ISC located at the +4 position from the bottom of the crypt (ISC+4) can both differentiate into absorptive or secretory intestinal epithelial cells. However, CBC and ISC+4 could have different metabolic, migratory functions, or stress survival.

Investigators designed a monocentric pilot study to develop intestinal organoids from endoscopic biopsies of IBD (Crohn and ulcerative colitis), FAP patients and healthy controls. Investigators plan to investigate the morphological characteristics of organoids, the expression of genes and proteins of the Wnt/APC/beta-catenin pathway within both ISC. Will also be studied the expression of key genes of tumor initiation (PTEN, BMPR1A, p53 and KRAS) and inflammatory parameters (cytokines and lipid mediators).

The results of this study could improve the understanding of intestine renewal. Later on, the development of new drugs could beneficiate to IBD and FAP patients.

Study Timeline

• Study First Submitted: 2016-05-13
• Study First Submitted QC: 2016-08-16
• Study First Posted: 2016-08-22
• Study Start: 2016-09
• Primary Completion: 2022-12
• Study Completion: 2023-12-27
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-09
• Last Update Posted: 2024-12-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 110

Inclusion Criteria

patient must have a coloscopy for intestinal pain -

Exclusion Criteria

cancer

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
FAP (familial adenomatous polyposis )	Endoscopic biopsies	arm composed by 30 patients with FAP disorder
ulcerative colitis	Endoscopic biopsies	arm composed by 30 patients with ulcerative colitis
witness	Endoscopic biopsies	arm composed by 30 patients with no intestinal disorders
Crohn disorder	Endoscopic biopsies	arm composed by 30 patients with Crohn disorder

Primary Outcome Measures

Name	Time	Method
number of organoids	2 days	number of organoids in culture wells during the follow-up

Secondary Outcome Measures

Name	Time	Method
mean size of organoids	2 days	mean diameter of organoids in culture wells during the follow-up
percentage of different types of organoids	2 days	organoids are differentiated by the size of the epithelial cell border and by the presence or absence of buds

Trial Locations

Locations (1)

Hopital des Enfants; 🇫🇷 Toulouse, France