Intestinal Mesenchymal Stem Stells and Inflammatory Bowel Diseases (COSMIC)

Characterization of Mesenchymal Stem Cells From the Colon and Small Intestine of Patients With Inflammatory Bowel Disease - The COSMIC Study

The exact origin of inflammatory bowel disease (IBD) is still unknown. The current hypothesis is that IBD is secondary to an abnormal intestinal immun response directed to all or part of the intestinal flora in genetically predisposed individuals. Several experimental studies have demonstrated the ability of mesenchymal stem cells (MSCs) from bone marrow or adipose tissue origin to control intestinal inflammation in animal models. However, to date, there are no data regarding the functions of resident MSCs in the colon and small intestine of IBD patients. We hypothesize that dysfunction of resident intestinal MSCs contributes to the disruption of intestinal homeostasis in patients with IBD causing the development of intestinal inflammation. The aim of this research project is to identify, describe and characterize at the molecular and functional level MSCs of the colon and small intestine of patients with Crohn's disease and ulcerative colitis and to compare them with a control population.

Study Overview

• Status: Terminated
• Conditions: Inflammatory Bowel Diseases
• Intervention / Treatment: Other: Intestinal biopsies during colonoscopy; Other: Biopsies taken on surgical specimen

Detailed Description

Primary and secondary objectives:

Main Objective: Characterize morphologically, molecularly and functionally the MSCs of colon and small intestine of patients with IBD and compared to MSCs of colon and small intestine of control patients.

Secondary objectives: To study the reaction of colon and small intestine MHC in patients with IBD following stimulation with bacterial compounds.

Methodology:

Clinical study exploratory translational physiopathological. Two groups of patients with Crohn's disease and ulcerative colitis who require colonoscopy or surgery for intestinal resection will be included. These two groups will be compared to a control group consisting of patients requiring colonoscopy for screening or intestinal resection for colorectal cancer or diverticulum.

Intestinal sampling by biopsy during the colonoscopy or with surgical specimen during the surgery will be performed to isolate the MSCs.

The outcome measures will be a qualitative and quantitative analysis of MSCs by immunohistochemistry, immunofluorescence, cell proliferation and differentiation, production of pro- and anti-inflammatory cytokines in the basal state and after bacterial stimulation.

Total of 60 patients (20 in groups, 15 with colonoscopy and 5 with surgical specimens).

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Montpellier, France, 34080
    • Hôpital St Eloi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• For IBD patients :

  • Age between 18 and 75 year old
  • Diagnosis of Crohn's disease or ulcertaive colitis according to internationla guidelines
  • Endoscopically active disease
  • Indication for colonoscopy or intestinal resection according to standard of care
  • Written inform consent

• For control patients :

  • Age between 18 and 75 year old
  • Indication for screening colonoscopy for irritable bowel syndrome, diverticulum or colorectal cancer surveillance according to standard of care
  • Indication for intestinal resection for diverticulum or colorectal cancer according to standard of care
  • Written inform consent

Exclusion criteria:

• For IBD patients :

  • Active intestinal infection
  • Confirmed intestinal parasitosis
  • Intestinal stoma

• For control patients :

  • Active intestinal infection
  • Confirmed intestinal parasitosis
  • Intestinal inflammation at colonoscopy
  • Chronic intestinal inflammation on biopsies
  • Absence of healthy tissue on surgical specimen

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Crohn's disease patient group; Intestinal biopsies during colonoscopy or biopsies taken on surgical specimen after intestinal resection	Other: Intestinal biopsies during colonoscopy; Intestinal biopsies during colonoscopy; Other: Biopsies taken on surgical specimen; biopsies taken on surgical specimen after intestinal resection
Other: Ulcerative colitis patient group; Intestinal biopsies during colonoscopy or biopsies taken on surgical specimen after intestinal resection	Other: Intestinal biopsies during colonoscopy; Intestinal biopsies during colonoscopy; Other: Biopsies taken on surgical specimen; biopsies taken on surgical specimen after intestinal resection
Other: Control group; Intestinal biopsies during colonoscopy or biopsies taken on surgical specimen after intestinal resection	Other: Intestinal biopsies during colonoscopy; Intestinal biopsies during colonoscopy; Other: Biopsies taken on surgical specimen; biopsies taken on surgical specimen after intestinal resection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proliferation and differentiation of intestinal MSCs in IBD patients.	Proliferation and differentiation of intestinal MSCs in IBD patients.	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of MSCs between IBD patients and control patients	Comparison of MSCs between IBD patients and control patients using mmunohistochemistry, immunofluorescence, quantification of pro- and anti-inflammatory cytokines production.	1 month

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Investigators: Principal Investigator: Guillaume Pineton de Chambrun, University Hospital, Montpellier

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2018
• Primary Completion (Actual): February 13, 2019
• Study Completion (Actual): February 13, 2019

Study Registration Dates

• First Submitted: April 10, 2017
• First Submitted That Met QC Criteria: April 10, 2017
• First Posted (Actual): April 14, 2017

Study Record Updates

• Last Update Posted (Actual): December 28, 2021
• Last Update Submitted That Met QC Criteria: December 27, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Crohn's disease; ulcerative colitis; mesenchymal stem cells; intestinal inflammation
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Intestinal Diseases
• Other Study ID Numbers: 9755 (Other Identifier: UK Clinical Research Network)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No