Clinical trial NCT03901235: MSC Intratissular Injection in Crohn Disease Patients
Official title: Treatment of Refractory Crohn's Disease Lesions by Local Injection of Mesenchymal Stem Cells
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Efficacy and Safety
Lead sponsor: University of Liege
Sponsor class: OTHER
Collaborators: name: Centre Hospitalier Universitaire de Liege
First posted: 2019-04-03
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Non-controlled, non-randomized, open label study
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Proportion of patients with deep ulcer healing
timeFrame: Week 12
measure: Proportion of patients with stricture healing
timeFrame: Week 12
measure: Proportion of patients with complex perianal fistula healing
timeFrame: Week 12
measure: Safety assessed by the incidence of treatment-emergent adverse events during the study period
timeFrame: from week 0 to week 48
Secondary outcomes:
measure: Evolution of clinical disease activity index
timeFrame: week 0, 12 and 48
measure: Evolution of Short health scale (quality of life)
timeFrame: week 0, 12 and 48
measure: Evolution of the Lemann Index (measuring cumulated intestinal damage in Crohn's disease)
timeFrame: week 0, 12 and 48
measure: Evolution of the " Group of Therapeutic Study of Inflammatory Disorders of the Digestive Tube" obstructive score for Crohn Disease strictures
timeFrame: weeks 0, 12 and 48
Other outcomes:
Locations:
city: Liège
country: Belgium
facility: CHU de Liège
Study officials:
affiliation: Centre Hospitalier Universitaire de Liege
name: Edouard Louis, Prof
role: PRINCIPAL_INVESTIGATOR
References: