Treatment of refractory Crohn's disease lesions by local injection of mesenchymal stem cells

Phase 1/2

Suspended

Conditions: Crohn's Disease

Registration Number: 2024-514033-37-00

Lead Sponsor: Centre hospitalier universitaire de Liege

Brief Summary: To assess the safety and efficacy of local injection of mesenchymal stem cells on healing of refractory intestinal and perianal lesions in Crohn’s disease

Detailed Description: Not available

Recruitment & Eligibility

Status: Temporarily halted

Sex: Not specified

Target Recruitment: 70

Inclusion Criteria

Patients ≥ 18 years of age

Patients signing the informed consent

Diagnosis of Crohn's Disease for more than 6 months

Presence of at least one CD lesion refractory to conventional therapies (azathioprine, 6- mercaptopurine or methotrexate) and to biologic treatments (anti-TNF 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)

15 patients with stricture(s), 5 patients with unhealed deep ulcer(s), and 50 patients with an actively draining perianal fistula(s) will be included.

Exclusion Criteria

Indication for immediate luminal surgery

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

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, GFR < 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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
The first co-primary endpoint will be the complete or partial healing of the refractory lesion at 12 weeks.		The first co-primary endpoint will be the complete or partial healing of the refractory lesion at 12 weeks.
The second co-primary endpoint is safety, assessed by monitoring for adverse and serious adverse events and changes in vital signs at the day of treatment and at all follow-up visits.		The second co-primary endpoint is safety, assessed by monitoring for adverse and serious adverse events and changes in vital signs at the day of treatment and at all follow-up visits.

Secondary Outcome Measures

Name	Time	Method
Complete or partial healing of the refractory lesion at 48 weeks		Complete or partial healing of the refractory lesion at 48 weeks
Evolution of the Patient Reported Outcomes (PRO), between week 0, 12 and 48, including pain, general well-being and number of stools per day		Evolution of the Patient Reported Outcomes (PRO), between week 0, 12 and 48, including pain, general well-being and number of stools per day
Evolution of Crohn's Disease Activity Index (CDAI) between weeks 0, 12 and 48		Evolution of Crohn's Disease Activity Index (CDAI) between weeks 0, 12 and 48
Evolution of the Short health scale SHS (quality of life) between week 0, 12 and 48		Evolution of the Short health scale SHS (quality of life) between week 0, 12 and 48
Evolution of the Lemann Index between week 0, 12 and 48		Evolution of the Lemann Index between week 0, 12 and 48
Evolution of the GETAID obstructive score for Crohn's Disease strictures between weeks 0, 12 and 48		Evolution of the GETAID obstructive score for Crohn's Disease strictures between weeks 0, 12 and 48
Disappearance or improvement of intestinal or colonic ulcers/stricture at MRI at 12 and 48 weeks		Disappearance or improvement of intestinal or colonic ulcers/stricture at MRI at 12 and 48 weeks
Incidence of specific safety outcomes all over the study period and more specifically at week 0, 4, 12, 24, and 48: (1) the occurrence of an obstruction requiring hospitalisation and fasting for at least 24 hours, (2) the occurrence of an intestinal perforation, (3) the development of an intra-abdominal fistula and/or abscess, (4) perianal abscess, (5) new perianal fistulous track.		Incidence of specific safety outcomes all over the study period and more specifically at week 0, 4, 12, 24, and 48: (1) the occurrence of an obstruction requiring hospitalisation and fasting for at least 24 hours, (2) the occurrence of an intestinal perforation, (3) the development of an intra-abdominal fistula and/or abscess, (4) perianal abscess, (5) new perianal fistulous track.

Trial Locations

Locations (1): Centre Hospitalier Universitaire De Liege
🇧🇪
Liege, Belgium
Centre Hospitalier Universitaire De Liege
🇧🇪Liege, Belgium
Edouard Louis
Site contact
+3243237256
edouard.louis@uliege.be