Clinical trial NCT04791878: Study of Mesenchymal Stem Cells for Pediatric Perianal Fistulizing Crohn's Disease
Official title: A Phase I Study of Adult Allogeneic Bone Marrow Derived Mesenchymal Stem Cells for Pediatric Perianal Fistulizing Crohn's Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Perianal Fistula Due to Crohn's Disease (Disorder)
Keywords: perianal
fistula
pediatric
crohn's disease
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
First posted: 2021-03-10
Enrollment: 10
Sex: ALL
Minimum age (years): 13
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study plans to enroll 10 patients aged 13-17 years of age with refractory perianal fistulizing disease. Patients will be treated by direct injection to the fistula tract(s) with 75 million allogeneic bone marrow derived mesenchymal stem cells at baseline and again after 3 months if not completely healed.

Detailed description: Crohn's disease (CD), a chronic transmural inflammatory disease of the gastrointestinal tract, continues to increase in incidence for unknown reasons. According to population based studies, at least 26% of patients with CD will develop perianal fistulas in the first two decades following diagnosis, particularly those with colonic and rectal involvement. These patients experience significant morbidity due to pain, persistent drainage, recurrent perianal sepsis, and ongoing need to access medical care resulting in increased costs and impaired quality of life. Onset of Crohn's disease in childhood is associated with even more aggressive perianal fistula development, with fistulas occurring in as many as 20-31% of children within 5-7 years after Crohn's disease diagnosis. Based on national estimates of pediatric Crohn's disease prevalence, this suggests that there are more than 10,000 children with perianal fistulas due to Crohn's disease in the United States.

This study plans to enroll 10 patients (aged 13-17 years) with refractory perianal fistulizing disease. The next step in management for these patients would be a mucosal tissue flap, temporary stoma, or proctectomy with permanent ostomy.

Patients will be treated by direct injection of 75 million allogeneic bone marrow derived mesenchymal stem cells at baseline and again after 3 months if not completely healed. Patients will be followed for a total of 12 months post initial injection.

Eligibility criteria: Inclusion Criteria

1. Males and females aged 13-17 with a diagnosis of Crohn's disease for at least six months duration.
2. Single and Multi-tract Perianal fistula, with or without previous failed surgical repair.
3. Have no contraindications to MR evaluations: e.g. pacemaker or magnetically active metal fragments, claustrophobia
4. Ability to comply with protocol
5. Competent and able to provide written informed consent
6. Concurrent Crohn's-related therapies with stable doses corticosteroids, 5- ASA drugs, immunomodulators, anti-TNF therapy, anti-integrin and anti-interleukin therapies are permitted.
7. Agree to use birth control or abstinence to avoid pregnancy during the study

Exclusion Criteria

1. Inability to give informed consent.
2. Clinically significant medical conditions within the six months before administration of MSCs: e.g. myocardial infarction, active angina, congestive heart failure or other conditions that would, in the opinion of the investigators, compromise the safety of the subject.
3. Specific exclusions:

   1. Hepatitis B or C
   2. HIV
   3. Abnormal AST or ALT at screening (defined as \>/+2x ULN)
4. History of colon cancer in the past two years, or treatment for other cancers within the last 6 months.
5. Investigational drug within one month of treatment
6. Pregnant or breast feeding or trying to become pregnant.
7. Presence of a rectovaginal or perineal body fistula
8. Change in Crohn's immunosuppressive regimen within the 2 months prior to enrollment
9. Uncontrolled intestinal Crohn's disease which will require escalation for medical therapy or surgery within 2 months of enrollment
10. Severe anal canal disease that is stenotic and requires dilation
11. Female participant unwilling to agree to use acceptable contraception methods during participation in study

Primary outcomes:
measure: Treatment related adverse events
timeFrame: Month 3
measure: Treatment related adverse events
timeFrame: Month 12
Secondary outcomes:
measure: Complete clinical healing
timeFrame: Month 3
measure: Complete clinical healing
timeFrame: Month 12
measure: Partial clinical healing
timeFrame: Month 3
measure: Partial clinical healing
timeFrame: Month 12
measure: Lack of response
timeFrame: Month 3
measure: Lack of response
timeFrame: Month 12
measure: Worsening of disease
timeFrame: Month 3
measure: Worsening of disease
timeFrame: Month 12
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
Study officials:
affiliation: The Cleveland Clinic
name: Amy Lightner, MD
role: PRINCIPAL_INVESTIGATOR
References:
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