MSC Intratissular Injection in Crohn Disease Patients (MSC)

Treatment of Refractory Crohn's Disease Lesions by Local Injection of Mesenchymal Stem Cells

The main objective is to assess the efficacy of local injection of MSC on the healing of refractory intestinal and perianal lesions in crohn disease. The second co-primary endpoint is safety.

Study Overview

• Status: Recruiting
• Conditions: Efficacy and Safety
• Intervention / Treatment: Biological: Mesenchymal Stromal Cells

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Edouard Louis, Prof; Phone Number: 0032 043667256; Email: edouard.louis@uliege.be
• Study Contact Backup: Name: Chantal Lechanteur; Phone Number: 0032 043668390; Email: c.lechanteur@chuliege.be

Study Locations

• Belgium
  • Liège, Belgium, 4000
    • Recruiting
    • Chu De Liège
    • Contact: Edouard Louis, Prof; Phone Number: 043667256 043667256; Email: edouard.louis@uliege.be
    • Contact: Layla Boutaffala; Phone Number: 0032 043668065; Email: lboutaffala@chuliege.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients ≥ 18 years of age
• Signing the informed consent
• Diagnosis of Crohn Disease for more than 6 months
• Presence of at least one Crohn Disease lesion refractory to conventional therapies (azathioprine, 6-mercaptopurine or methotrexate) and to biologic treatments (anti-Tumor Necrosis Factor therapies, vedolizumab, or ustekinumab).
• Refractory lesion defined by (1) a stricture with a length of 2 to 5cm of the colon or the ileum accessible by ileocolonoscopy (i.e. a lesion identified during a colonoscopy with a lumen narrowing non passable by the colonoscope), (2) unhealed deep ulcer of the colon or the ileum accessible to ileocolonoscopy, or (3) actively draining perianal fistula(s).
• Twenty patients with stricture(s), 20 patients with unhealed deep ulcer(s), and 20 patients with an actively draining perianal fistula(s) will be included

Exclusion Criteria:

• Indication for immediate luminal surgery
• Intestinal obstruction
• Intra-abdominal fistulas or abscess
• Intestinal/colonic stricture or deep unhealed ulcer not accessible to ileocolonoscopy
• Undrained peri-anal abscess
• Pregnant women or planning pregnancy within one year
• Positive stool culture/toxin for clostridium difficile pathogen or other pathogens
• Renal failure (anuria, serious fluid overload, Glomerular Filtration Rate < 30 ml/min, dialysis) or hepatic failure (Fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin >3 mg/dL)
• documented human immunodeficiency virus infection; active hepatitis B, C, or tuberculosis
• an opportunistic infection within 6 months before screening or a serious infection in the previous 3 months
• malignancy within the past 5 years; or a history of lymphoproliferative disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mesenchymal Stromal Cells	Biological: Mesenchymal Stromal Cells; Suspension of mesenchymal stromal cells for intratissular injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with deep ulcer healing	Complete deep ulcer healing is defined by the disappearance of the ulcer; partial healing is defined by a decrease in the depth or the diameter of the ulcer.	Week 12
Proportion of patients with stricture healing	Complete stricture healing is defined by the ability to pass the ileocolonoscope through the stricture; partial healing is defined by the increase in the diameter of the stricture.	Week 12
Proportion of patients with complex perianal fistula healing	Complete complex perianal fistula healing is defined by the complete closure of the external fistula opening, no drainage upon gentle pressure, no abscess. And by looking at the size of the fistulous track, presence of collection, and gadolinium enhancement by MRI	Week 12
Safety assessed by the incidence of treatment-emergent adverse events during the study period	Assessment of the incidence of adverse and serious adverse events over the 48 weeks study period. Toxicity grade of adverse events is determined using the Common Terminology Criteria for Adverse Events (version 4.0). Relationship to the therapeutic procedure will systematically be assessed.	from week 0 to week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evolution of clinical disease activity index	Assess disease activity in Crohn's disease over 7 days using the Crohn's disease activity index	week 0, 12 and 48
Evolution of Short health scale (quality of life)	min : 0 - max : 10 (worse)	week 0, 12 and 48
Evolution of the Lemann Index (measuring cumulated intestinal damage in Crohn's disease)	which incorporates clinical, surgical, endoscopic, and imaging findings from all segments of the digestive tract into one composite score	week 0, 12 and 48
Evolution of the " Group of Therapeutic Study of Inflammatory Disorders of the Digestive Tube" obstructive score for Crohn Disease strictures	Grade : from 0 to higher value 6	weeks 0, 12 and 48

Collaborators and Investigators

• Sponsor: University of Liege
• Collaborators: Centre Hospitalier Universitaire de Liege
• Investigators: Principal Investigator: Edouard Louis, Prof, Centre Hospitalier Universitaire de Liège

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2018
• Primary Completion (Anticipated): December 31, 2025
• Study Completion (Anticipated): December 31, 2026

Study Registration Dates

• First Submitted: March 4, 2019
• First Submitted That Met QC Criteria: April 2, 2019
• First Posted (Actual): April 3, 2019

Study Record Updates

• Last Update Posted (Actual): May 10, 2023
• Last Update Submitted That Met QC Criteria: May 9, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: TJT1707P1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No