Back to resultsStudy of Mesenchymal Stem Cells for Pediatric Perianal Fistulizing Crohn's Disease
Primary Purpose
Perianal Fistula Due to Crohn's Disease (Disorder)
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Mesenchymal stem cells
Sponsored by
About this trial
This is an interventional treatment trial for Perianal Fistula Due to Crohn's Disease (Disorder) focused on measuring perianal, fistula, pediatric, crohn's disease
Eligibility Criteria
Inclusion Criteria
- Males and females aged 13-17 with a diagnosis of Crohn's disease for at least six months duration.
- Single and Multi-tract Perianal fistula, with or without previous failed surgical repair.
- Have no contraindications to MR evaluations: e.g. pacemaker or magnetically active metal fragments, claustrophobia
- Ability to comply with protocol
- Competent and able to provide written informed consent
- Concurrent Crohn's-related therapies with stable doses corticosteroids, 5- ASA drugs, immunomodulators, anti-TNF therapy, anti-integrin and anti-interleukin therapies are permitted.
- Agree to use birth control or abstinence to avoid pregnancy during the study
Exclusion Criteria
- Inability to give informed consent.
- 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.
Specific exclusions:
- Hepatitis B or C
- HIV
- Abnormal AST or ALT at screening (defined as >/+2x ULN)
- History of colon cancer in the past two years, or treatment for other cancers within the last 6 months.
- Investigational drug within one month of treatment
- Pregnant or breast feeding or trying to become pregnant.
- Presence of a rectovaginal or perineal body fistula
- Change in Crohn's immunosuppressive regimen within the 2 months prior to enrollment
- Uncontrolled intestinal Crohn's disease which will require escalation for medical therapy or surgery within 2 months of enrollment
- Severe anal canal disease that is stenotic and requires dilation
- Female participant unwilling to agree to use acceptable contraception methods during participation in study
Sites / Locations
- Cleveland ClinicRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Mesenchymal stem cells
Arm Description
allogeneic bone marrow derived mesenchymal stem cells
Outcomes
Primary Outcome Measures
Treatment related adverse events
Number of participants with treatment related adverse events post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease as assessed by protocol
Treatment related adverse events
Number of participants with treatment related adverse events post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease as assessed by protocol
Secondary Outcome Measures
Complete clinical healing
Number of participants with complete clinical healing post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease.
Complete Healing is defined as:
Radiographic Healing: MRI with an absence of a fluid collection >2 cm in 3 of 3 dimensions, lack of edema, inflammation or sign of active inflammatory response. A remnant scar of a fistula tract may remain
Clinical Healing: 100% cessation of drainage on both clinical exam with deep palpation and per patient report and epithelization of the external fistula opening
Complete clinical healing
Number of participants with complete clinical healing post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease.
Complete Healing is defined as:
Radiographic Healing: MRI with an absence of a fluid collection >2 cm in 3 of 3 dimensions, lack of edema, inflammation or sign of active inflammatory response. A remnant scar of a fistula tract may remain
Clinical Healing: 100% cessation of drainage on both clinical exam with deep palpation and per patient report and epithelization of the external fistula opening
Partial clinical healing
Number of participants with partial clinical healing post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease
Partial clinical healing is defined as:
Radiographic Healing: MRI with an absence of a fluid collection >2 cm in 2 of 3 dimensions, lack of edema, inflammation or sign of active inflammatory response. A remnant scar of a fistula tract may remain
Clinical healing: Greater than or equal to 50 % cessation of drainage on both clinical exam with deep palpation and per patient report and epithelization of the external fistula opening
Partial clinical healing
Number of participants with partial clinical healing post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease
Partial clinical healing is defined as:
Radiographic Healing: MRI with an absence of a fluid collection >2 cm in 2 of 3 dimensions, lack of edema, inflammation or sign of active inflammatory response. A remnant scar of a fistula tract may remain
Clinical healing: Greater than or equal to 50 % cessation of drainage on both clinical exam with deep palpation and per patient report and epithelization of the external fistula opening
Lack of response
Number of participants with lack of response post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease
Lack of response is defined as:
Radiographic and Clinical healing which does not meet the threshold for Partial Healing
Lack of response
Number of participants with lack of response post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease
Lack of response is defined as:
Radiographic and Clinical healing which does not meet the threshold for Partial Healing
Worsening of disease
Number of participants with worsening of disease post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease
Worsening disease is defined as:
Radiographic: MRI with a fluid collection >2 cm in 2 of 3 dimensions, edema, inflammation or sign of active inflammatory response. An increased number of tracts may be seen, or increased branching from the primary tract,
Clinical: Increased drainage per patient report and on clinical exam
Worsening of disease
Number of participants with worsening of disease post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease
Worsening disease is defined as:
Radiographic: MRI with a fluid collection >2 cm in 2 of 3 dimensions, edema, inflammation or sign of active inflammatory response. An increased number of tracts may be seen, or increased branching from the primary tract,
Clinical: Increased drainage per patient report and on clinical exam
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04791878
Brief Title
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
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Recruiting
Study Start Date
April 1, 2021 (Actual)
Primary Completion Date
April 1, 2023 (Anticipated)
Study Completion Date
April 1, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Amy Lightner
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Perianal Fistula Due to Crohn's Disease (Disorder)
Keywords
perianal, fistula, pediatric, crohn's disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Mesenchymal stem cells
Arm Type
Experimental
Arm Description
allogeneic bone marrow derived mesenchymal stem cells
Intervention Type
Drug
Intervention Name(s)
Mesenchymal stem cells
Intervention Description
Direct injection of 75 million allogeneic bone marrow derived mesenchymal stem cells at baseline and again after 3 months if not completely healed
Primary Outcome Measure Information:
Title
Treatment related adverse events
Description
Number of participants with treatment related adverse events post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease as assessed by protocol
Time Frame
Month 3
Title
Treatment related adverse events
Description
Number of participants with treatment related adverse events post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease as assessed by protocol
Time Frame
Month 12
Secondary Outcome Measure Information:
Title
Complete clinical healing
Description
Number of participants with complete clinical healing post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease.
Complete Healing is defined as:
Radiographic Healing: MRI with an absence of a fluid collection >2 cm in 3 of 3 dimensions, lack of edema, inflammation or sign of active inflammatory response. A remnant scar of a fistula tract may remain
Clinical Healing: 100% cessation of drainage on both clinical exam with deep palpation and per patient report and epithelization of the external fistula opening
Time Frame
Month 3
Title
Complete clinical healing
Description
Number of participants with complete clinical healing post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease.
Complete Healing is defined as:
Radiographic Healing: MRI with an absence of a fluid collection >2 cm in 3 of 3 dimensions, lack of edema, inflammation or sign of active inflammatory response. A remnant scar of a fistula tract may remain
Clinical Healing: 100% cessation of drainage on both clinical exam with deep palpation and per patient report and epithelization of the external fistula opening
Time Frame
Month 12
Title
Partial clinical healing
Description
Number of participants with partial clinical healing post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease
Partial clinical healing is defined as:
Radiographic Healing: MRI with an absence of a fluid collection >2 cm in 2 of 3 dimensions, lack of edema, inflammation or sign of active inflammatory response. A remnant scar of a fistula tract may remain
Clinical healing: Greater than or equal to 50 % cessation of drainage on both clinical exam with deep palpation and per patient report and epithelization of the external fistula opening
Time Frame
Month 3
Title
Partial clinical healing
Description
Number of participants with partial clinical healing post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease
Partial clinical healing is defined as:
Radiographic Healing: MRI with an absence of a fluid collection >2 cm in 2 of 3 dimensions, lack of edema, inflammation or sign of active inflammatory response. A remnant scar of a fistula tract may remain
Clinical healing: Greater than or equal to 50 % cessation of drainage on both clinical exam with deep palpation and per patient report and epithelization of the external fistula opening
Time Frame
Month 12
Title
Lack of response
Description
Number of participants with lack of response post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease
Lack of response is defined as:
Radiographic and Clinical healing which does not meet the threshold for Partial Healing
Time Frame
Month 3
Title
Lack of response
Description
Number of participants with lack of response post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease
Lack of response is defined as:
Radiographic and Clinical healing which does not meet the threshold for Partial Healing
Time Frame
Month 12
Title
Worsening of disease
Description
Number of participants with worsening of disease post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease
Worsening disease is defined as:
Radiographic: MRI with a fluid collection >2 cm in 2 of 3 dimensions, edema, inflammation or sign of active inflammatory response. An increased number of tracts may be seen, or increased branching from the primary tract,
Clinical: Increased drainage per patient report and on clinical exam
Time Frame
Month 3
Title
Worsening of disease
Description
Number of participants with worsening of disease post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease
Worsening disease is defined as:
Radiographic: MRI with a fluid collection >2 cm in 2 of 3 dimensions, edema, inflammation or sign of active inflammatory response. An increased number of tracts may be seen, or increased branching from the primary tract,
Clinical: Increased drainage per patient report and on clinical exam
Time Frame
Month 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
13 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria
Males and females aged 13-17 with a diagnosis of Crohn's disease for at least six months duration.
Single and Multi-tract Perianal fistula, with or without previous failed surgical repair.
Have no contraindications to MR evaluations: e.g. pacemaker or magnetically active metal fragments, claustrophobia
Ability to comply with protocol
Competent and able to provide written informed consent
Concurrent Crohn's-related therapies with stable doses corticosteroids, 5- ASA drugs, immunomodulators, anti-TNF therapy, anti-integrin and anti-interleukin therapies are permitted.
Agree to use birth control or abstinence to avoid pregnancy during the study
Exclusion Criteria
Inability to give informed consent.
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.
Specific exclusions:
Hepatitis B or C
HIV
Abnormal AST or ALT at screening (defined as >/+2x ULN)
History of colon cancer in the past two years, or treatment for other cancers within the last 6 months.
Investigational drug within one month of treatment
Pregnant or breast feeding or trying to become pregnant.
Presence of a rectovaginal or perineal body fistula
Change in Crohn's immunosuppressive regimen within the 2 months prior to enrollment
Uncontrolled intestinal Crohn's disease which will require escalation for medical therapy or surgery within 2 months of enrollment
Severe anal canal disease that is stenotic and requires dilation
Female participant unwilling to agree to use acceptable contraception methods during participation in study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Allison Bayles
Phone
216-444-0887
Email
ibdstemcelltherapy@ccf.org
First Name & Middle Initial & Last Name or Official Title & Degree
Alex VanDenBossche, BSN
Phone
215-370=0307
Email
ibdstemcelltherapy@ccf.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amy Lightner, MD
Organizational Affiliation
The Cleveland Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Allison Bayles
Phone
216-444-0887
Email
ibdstemcelltherapy@ccf.org
First Name & Middle Initial & Last Name & Degree
Amy Lightner, MD
12. IPD Sharing Statement
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Study of Mesenchymal Stem Cells for Pediatric Perianal Fistulizing Crohn's Disease
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