- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02166021
Clinical Efficacy of Autologous Mesenchymal Bone Marrow Stem Cells in Active & Progressive Multiple Sclerosis
Phase 2 Trial to Investigate the Clinical Efficacy & the Optimal Administration (Based on the Immunological, Clinical & Neuroradiological Effects) of Autologous Mesenchymal Bone Marrow Stem Cells in Active & Progressive Multiple Sclerosis
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Mesenchymal stem cells (MSC) induce immune-modulatory and neurotrophic effects and were shown to have an acceptable safety profile for clinical applications. We aimed to evaluate the safety and efficacy of MSC transplantation in active progressive MS and investigate possible neuroprotective effects.
Methods: This single-center double-blind crossover trial enrolled 48 patients with progressive MS (expanded disability status scale (EDSS) range: 3.5-6.5, mean: 5.6+/-0.8). Patients were randomised into three groups and treated intrathecally (IT) or intravenously (IV) with autologous MSCs (1x106/Kg) or placebo. At 6-months, treatment groups were crossed over and patients re-treated with either MSC or placebo. During the 2-months run-in period and the 12-months after treatment, participants were followed using EDSS, 25-foot timed walking, 9-hole peg test, neurocognitive tests, quantitative magnetic resonance imaging (MRI), functional MRI, optic coherence tomography (OCT), visual evoked potentials (VEP), and dynamic visual tests.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Jerusalem, Israel, 91120
- Hadassah Medical Organization
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Consenting patients fulfilling the Poser's clinical criteria for definite MS
- Age: 18-65, males and females
- Duration of disease: >3 years
- Progressive form of MS: PPMS, SPMS (with/without relapses)
- EDSS score of 3.5 - 6.5
- Failure to currently available, registered - first and second line immunomodulatory treatments (at least one).
- Evidence for new activity of MS during the 3 months before the injection of MSC.
Exclusion Criteria:
- Patients who were treated with cytotoxic medications during the last 3 months prior to the inclusion.
- Patients suffering from significant cardiac, renal or hepatic failure or any other disease that may risk the patient or interfere with the ability to interpret the results
- Patients with active infections
- Patients with severe cognitive decline or inability to understand and sign the informed consent
- Patients who received any cellular treatment in the past
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: IT- Treated
Injection to IT (Group 1).
After 6 months, 8 patients (group 1A) will be treated with MSC once again in IT, and 8 additional patients (group 1B) will receive a placebo.
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A culture of purified MSCs was prepared under aseptic conditions, and cultured for 4 weeks, until they reached confluency, and were then harvested.
After sterility was confirmed, the cells resuspended in normal saline at a concentration of 10 × 106/mL to 15 × 106/mL.
Other Names:
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Experimental: IV - Treated
Injection to IV (Group 2).
After 6 months, 8 patients (group 2A) will be treated with MSC once again in IV, and 8 additional patients (group 2B) will receive a placebo.
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A culture of purified MSCs was prepared under aseptic conditions, and cultured for 4 weeks, until they reached confluency, and were then harvested.
After sterility was confirmed, the cells resuspended in normal saline at a concentration of 10 × 106/mL to 15 × 106/mL.
Other Names:
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Placebo Comparator: Placebo
Placebo at the first injection (group 3).
After 6 months, 8 patients (group 3A) will be treated with MSC in IT, and 8 additional patients (group 3B) will be treated with MSC in IV.
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A culture of purified MSCs was prepared under aseptic conditions, and cultured for 4 weeks, until they reached confluency, and were then harvested.
After sterility was confirmed, the cells resuspended in normal saline at a concentration of 10 × 106/mL to 15 × 106/mL.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety Assessment
Time Frame: 6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group
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The proportions of the patients in the three treatment-groups (MSC-IV, MSC-IT and placebo) who experienced any adverse event.
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6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group
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Neurological efficacy
Time Frame: 6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group
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The proportions of the patients with treatment failure (increase of the EDSS by 1 point for patients with baseline values of 5.0 or less and of 0.5 degree for baseline EDSS of more than 5.0), confirmed by two consecutive evaluations, in the three treatment-groups.
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6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
EDSS score
Time Frame: 6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group
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Change from baseline to 6 months visit post each treatment cycle in EDSS following treatment with intravenous or intrathecal MSC infusion, vs. placebo treatment in MS patients at 6 months post treatment.
[A decrease in EDSS indicates clinical improvement].
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6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group
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Ambulation score
Time Frame: 6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group
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Change from baseline to 6 months visit post each treatment cycle in ambulation score following treatment with intravenous or intrathecal MSC infusion, vs. placebo treatment in MS patients at 6 months post treatment.
[A decrease in ambulation score indicates clinical improvement].
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6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group
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Functional scores
Time Frame: 6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group
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Change from baseline to 6 months visit post each treatment cycle in the sum of all functional scores (from the EDSS scoring) following treatment with intravenous or intrathecal MSC infusion, vs. placebo treatment in MS patients at 6 months post treatment.
[A decrease in the sum of functional scores indicates clinical improvement].
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6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group
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Single injection vs. repeated MSCs injection
Time Frame: 12 months: ie the total duration of the trial
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Change from baseline to final 12-month visit, in EDSS following treatment of a single injection of MSCs vs. repeated MSCs injections treatment. [A decrease in EDSS indicates clinical improvement]. *similar comparison will be performed for the ambulation score and the sum of all functional systems' scores |
12 months: ie the total duration of the trial
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Relapse rate
Time Frame: 12 months: ie the total duration of the trial
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Annualized MS-Relapse rate during the 6 months of each treatment cycle, in the three treatment groups.
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12 months: ie the total duration of the trial
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T2-weighted flair lesions load in MRI
Time Frame: 6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group
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The annualized rate of change in the total lesions load of the T2-weighted MRI scans during the 6 months of each cycle of treatment versus the rate of change in the run-in period (before the treatment).
[An increase in the volume of lesions indicates progression of the disease].
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6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group
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Total brain volume in MRI
Time Frame: 6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group
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The annualized rate of change in total brain volume in MRI scans during the 6 months of each cycle of treatment versus the rate of change in the run-in period (before the treatment).
[A decrease in the brain volume indicates progression of the disease].
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6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group
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Gadolinium enhancing lesions in MRI
Time Frame: 6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group
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The mean annualized number of gadolinium-enhancing lesions during the 6 months of each treatment cycle, in the three treatment groups.
[The appearance of gadolinium-enhancing lesions in MRI indicates activity of the disease].
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6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group
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Functional MRI
Time Frame: 6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group
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The annualized rate of change in the z-scores of the motor networks in resting functional MRI during the 6 months of each cycle of treatment versus the rate of change in the run-in period (before the treatment). [An increase in the z-score indicates functional improvement]. * similar measurements will apply for the pyramidal and visual networks |
6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group
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25-feet timed walking
Time Frame: 6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group
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The mean time to walk 25-feet during the 6 months in each treatment cycle vs the mean time during the run-in pre-treatment period.
[A decrease in the value of timed walking indicates clinical improvement].
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6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group
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9-hole peg test
Time Frame: 6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group
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The mean time to perform the 9-hole peg test of hands dexterity during the 6 months in each treatment cycle vs the mean time during the run-in pre-treatment period.
[A decrease in the value of timed walking indicates clinical improvement].
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6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group
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Paced Auditory Serial Addition Test (PASAT)
Time Frame: 6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group
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The score given in this neuropsychological test reflects the assess capacity and rate of information processing and sustained and divided attention.
This perform during the 6 months in each treatment cycle vs the mean time during the run-in pre-treatment period.
[An increase in z score indicates clinical improvement]
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6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group
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Cognitive function: Controlled Oral Word Association Test (COWAT)
Time Frame: 6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group
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The annualized rate of change in the z-scores of the COWAT cognitive test during the 6 months of each cycle of treatment versus the rate of change in the run-in period (before the treatment). [An increase in the z-score indicates functional improvement]. * similar measurements will apply for other cognitive tests (SDMT) |
6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group
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Optical coherence tomography (OCT)
Time Frame: 6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group
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Change from baseline to 6 months visit, post each treatment cycle retinal nerve fiber layer (RNFL) thickness in OCT, following treatment with intravenous or intrathecal MSC infusion, vs. placebo treatment in MS patients at 6 months post treatment. [An increase in RNFL thickness indicates clinical improvement]. * similar measurements will apply for Macula thickness |
6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group
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Immunology
Time Frame: 6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group
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Change from baseline to 6 months visit post each treatment cycle in the proportion of the lymphocytes expressing the CD4+CD25+ markers (T-regulatory cells) following treatment with intravenous or intrathecal MSC infusion, vs. placebo treatment at 6 months post treatment. [An increase in the proportion may indicate beneficial effects]. * similar measurements (for evaluation of safety of the treatment) will be performed for additional white blood cell subpopulations |
6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group
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Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Hadas Lemberg, PhD, Director, R&D Division
Publications and helpful links
General Publications
- Petrou P, Kassis I, Ginzberg A, Hallimi M, Karussis D. Effects of Mesenchymal Stem Cell Transplantation on Cerebrospinal Fluid Biomarkers in Progressive Multiple Sclerosis. Stem Cells Transl Med. 2022 Mar 3;11(1):55-58. doi: 10.1093/stcltm/szab017.
- Petrou P, Kassis I, Levin N, Paul F, Backner Y, Benoliel T, Oertel FC, Scheel M, Hallimi M, Yaghmour N, Hur TB, Ginzberg A, Levy Y, Abramsky O, Karussis D. Beneficial effects of autologous mesenchymal stem cell transplantation in active progressive multiple sclerosis. Brain. 2020 Dec 1;143(12):3574-3588. doi: 10.1093/brain/awaa333.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- MSC-MS-001-IL
Drug and device information, study documents
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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