Autologous Mesenchymal Stem Cell (MSC) Transplantation in MS
Primary Purpose
Relapsing-Remitting Multiple Sclerosis, Secondary Progressive Multiple Sclerosis, Progressive Relapsing Multiple Sclerosis
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Autologous mesenchymal stem cell transplantation
Sponsored by
About this trial
This is an interventional treatment trial for Relapsing-Remitting Multiple Sclerosis focused on measuring Mesenchymal Stem Cell, MSC, Autologous, Multiple Sclerosis
Eligibility Criteria
Inclusion Criteria:
- Age 18 to 55, inclusive.
- Diagnosis of MS
- Relapsing form of MS (relapsing-remitting, secondary progressive, or progressive-relapsing course).
- EDSS score 3.0-6.5, inclusive. (Must be able to walk)
- Active disease during prior 24 months.
- Documented evidence of involvement of the anterior afferent visual system: previous optic neuritis, optic atrophy or an afferent pupillary defect on exam, RNFL thickness on OCT <LLN in at least one eye OR documented VEP latency in at least 1 eye.
- Cranial MRI scan demonstrating T2-hyperintense lesions satisfying diagnostic criteria for MS
- Ability to perform the component tests of the MSFC (T25FW, 9HPT, PASAT3).
- Ability to perform SLCLA.
- Has given written informed consent to participate in the study.
Exclusion Criteria:
- A clinically significant infectious illness (e.g., cellulitis, abscess, pneumonia, septicemia) within 30 days of the Screening Visit.
- History of cancer other than basal cell carcinoma of the skin.
- History or laboratory results indicative of any significant cardiac, endocrine, hematologic, hepatic, immunologic, infectious, metabolic, urologic, pulmonary, gastrointestinal, dermatologic, psychiatric, renal, neoplastic, or other disorder that in the opinion of the Principal Investigator would preclude the safe performance of BM aspiration, infusion of autologous MSCs, or performance of any of the planned study assessments.
- Abnormal blood tests which exceed designated limits.
- Positive screening tests for hepatitis B, hepatitis C, HIV 1&2, HTLV I/II, CMV, West Nile virus, syphilis, blood parasite infection.
- Clinically significant abnormality on chest X-ray.
- Clinically significant abnormality on EKG.
- Oxygen-saturation <90% on room air.
- History of alcohol or drug abuse within one year.
- Any metallic material or electronic device in the body, or condition that precludes the participant from undergoing MRI with Gd administration.
- Uncontrolled glaucoma or other ocular condition that precludes performing OCT or interpreting the results.
- MS relapse with onset within 30 days prior to the Screening Visit or the participant has not stabilized from a previous relapse at the time of the Screening Visit.
- Current treatment with an investigational MS disease therapy.
- Prior treatment with:
Total lymphoid irradiation. Cladribine. T-cell or T-cell receptor vaccination. Campath-1h (alemtuzumab). Rituxan (rituximab).
- Prior treatment within three months with:
Tysabri (natalizumab). Gilenya (Fingolimod/FTY720). Zenapax (daclizumab). Cytoxan (cyclophosphamide). Novantrone (mitoxantrone). Cyclosporine. CellCept (mycophenolate mofetil). Imuran (azathioprine). Rheumatrex (methotrexate). IV gamma globulin. Plasma exchange.
- Prior treatment within one month:
Systemic corticosteroids with daily dose equivalent to Prednisone 60 mg or greater.
- Female participants who are not post-menopausal for at least one year, not surgically sterile, or not willing to practice effective contraception.
- Nursing mothers, pregnant women, or women planning to become pregnant during the study.
- Male participants who are not willing to practice effective contraception.
- Unwillingness or inability to comply with the requirements of this protocol including the presence of any condition (physical, mental, or social) that, in the opinion of the Principal Investigator, is likely to affect the participant's ability to comply with the study protocol.
- Any other reason that, in the opinion of the Principal Investigator, makes the participant unsuitable for participation in the study.
Sites / Locations
- Cleveland Clinic Mellen Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Autologous MSC transplantation
Arm Description
Outcomes
Primary Outcome Measures
To evaluate the feasibility of culturing MSCs, and infusion-related safety and tolerability of autologous MSC transplantation over one month in patients with relapsing forms of MS
Secondary Outcome Measures
To evaluate effects on MS disease activity measured by the number of Gd-enhancing brain MRI lesions
To evaluate safety and tolerability of autologous MSC transplantation over 6 months
Full Information
NCT ID
NCT00813969
First Posted
December 22, 2008
Last Updated
March 28, 2016
Sponsor
The Cleveland Clinic
Collaborators
University Hospitals Cleveland Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT00813969
Brief Title
Autologous Mesenchymal Stem Cell (MSC) Transplantation in MS
Official Title
A Phase I Study to Assess the Feasibility, Safety, and Tolerability of Autologous Mesenchymal Stem Cell Transplantation in Patients With Relapsing Forms of Multiple Sclerosis
Study Type
Interventional
2. Study Status
Record Verification Date
March 2016
Overall Recruitment Status
Completed
Study Start Date
March 2011 (undefined)
Primary Completion Date
January 2014 (Actual)
Study Completion Date
May 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The Cleveland Clinic
Collaborators
University Hospitals Cleveland Medical Center
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The study is an investigator-run, open-label Phase 1 safety study of autologous mesenchymal stem cell transplantation, involving approximately 24 ambulatory participants with relapsing forms of MS (approximately equal numbers with relapsing-remitting and secondary progressive/ progressive relapsing MS) and evidence of involvement of the anterior afferent visual system.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsing-Remitting Multiple Sclerosis, Secondary Progressive Multiple Sclerosis, Progressive Relapsing Multiple Sclerosis
Keywords
Mesenchymal Stem Cell, MSC, Autologous, Multiple Sclerosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Autologous MSC transplantation
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
Autologous mesenchymal stem cell transplantation
Intervention Description
A single IV infusion of up to 2 million cells per kg based on the MSC numbers achieved after culture expansion
Primary Outcome Measure Information:
Title
To evaluate the feasibility of culturing MSCs, and infusion-related safety and tolerability of autologous MSC transplantation over one month in patients with relapsing forms of MS
Time Frame
1 month
Secondary Outcome Measure Information:
Title
To evaluate effects on MS disease activity measured by the number of Gd-enhancing brain MRI lesions
Time Frame
1 month
Title
To evaluate safety and tolerability of autologous MSC transplantation over 6 months
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age 18 to 55, inclusive.
Diagnosis of MS
Relapsing form of MS (relapsing-remitting, secondary progressive, or progressive-relapsing course).
EDSS score 3.0-6.5, inclusive. (Must be able to walk)
Active disease during prior 24 months.
Documented evidence of involvement of the anterior afferent visual system: previous optic neuritis, optic atrophy or an afferent pupillary defect on exam, RNFL thickness on OCT <LLN in at least one eye OR documented VEP latency in at least 1 eye.
Cranial MRI scan demonstrating T2-hyperintense lesions satisfying diagnostic criteria for MS
Ability to perform the component tests of the MSFC (T25FW, 9HPT, PASAT3).
Ability to perform SLCLA.
Has given written informed consent to participate in the study.
Exclusion Criteria:
A clinically significant infectious illness (e.g., cellulitis, abscess, pneumonia, septicemia) within 30 days of the Screening Visit.
History of cancer other than basal cell carcinoma of the skin.
History or laboratory results indicative of any significant cardiac, endocrine, hematologic, hepatic, immunologic, infectious, metabolic, urologic, pulmonary, gastrointestinal, dermatologic, psychiatric, renal, neoplastic, or other disorder that in the opinion of the Principal Investigator would preclude the safe performance of BM aspiration, infusion of autologous MSCs, or performance of any of the planned study assessments.
Abnormal blood tests which exceed designated limits.
Positive screening tests for hepatitis B, hepatitis C, HIV 1&2, HTLV I/II, CMV, West Nile virus, syphilis, blood parasite infection.
Clinically significant abnormality on chest X-ray.
Clinically significant abnormality on EKG.
Oxygen-saturation <90% on room air.
History of alcohol or drug abuse within one year.
Any metallic material or electronic device in the body, or condition that precludes the participant from undergoing MRI with Gd administration.
Uncontrolled glaucoma or other ocular condition that precludes performing OCT or interpreting the results.
MS relapse with onset within 30 days prior to the Screening Visit or the participant has not stabilized from a previous relapse at the time of the Screening Visit.
Current treatment with an investigational MS disease therapy.
Prior treatment with:
Total lymphoid irradiation. Cladribine. T-cell or T-cell receptor vaccination. Campath-1h (alemtuzumab). Rituxan (rituximab).
Prior treatment within three months with:
Tysabri (natalizumab). Gilenya (Fingolimod/FTY720). Zenapax (daclizumab). Cytoxan (cyclophosphamide). Novantrone (mitoxantrone). Cyclosporine. CellCept (mycophenolate mofetil). Imuran (azathioprine). Rheumatrex (methotrexate). IV gamma globulin. Plasma exchange.
Prior treatment within one month:
Systemic corticosteroids with daily dose equivalent to Prednisone 60 mg or greater.
Female participants who are not post-menopausal for at least one year, not surgically sterile, or not willing to practice effective contraception.
Nursing mothers, pregnant women, or women planning to become pregnant during the study.
Male participants who are not willing to practice effective contraception.
Unwillingness or inability to comply with the requirements of this protocol including the presence of any condition (physical, mental, or social) that, in the opinion of the Principal Investigator, is likely to affect the participant's ability to comply with the study protocol.
Any other reason that, in the opinion of the Principal Investigator, makes the participant unsuitable for participation in the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeffrey A Cohen, M.D.
Organizational Affiliation
The Cleveland Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cleveland Clinic Mellen Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
28381130
Citation
Cohen JA, Imrey PB, Planchon SM, Bermel RA, Fisher E, Fox RJ, Bar-Or A, Sharp SL, Skaramagas TT, Jagodnik P, Karafa M, Morrison S, Reese Koc J, Gerson SL, Lazarus HM. Pilot trial of intravenous autologous culture-expanded mesenchymal stem cell transplantation in multiple sclerosis. Mult Scler. 2018 Apr;24(4):501-511. doi: 10.1177/1352458517703802. Epub 2017 Apr 6.
Results Reference
derived
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Autologous Mesenchymal Stem Cell (MSC) Transplantation in MS
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