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NCT Number: NCT02166021

Clinical Efficacy of Autologous Mesenchymal Bone Marrow Stem Cells in Active & Progressive Multiple Sclerosis

The purpose of this study is to evaluate the clinical efficacy and the optimal way of administration of autologous mesenchymal bone marrow stem cells (MSC) compering intravenous injection and intrathecal injection vs. placebo, in active-progressive Multiple Sclerosis patients.

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Key information

Conditions

Multiple Sclerosis (MS) Autoimmune Diseases Autoimmune Diseases of the Nervous System Demyelinating Autoimmune Diseases, CNS Demyelinating Diseases Immune System Diseases Multiple Sclerosis Nervous System Diseases

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Hadassah Medical Organization

Jerusalem, 91120, Israel

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Mesenchymal stem cells

Biological

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: Autologous MSC

Primary outcomes

  1. 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

    The proportions of the patients in the three treatment-groups (MSC-IV, MSC-IT and placebo) who experienced any adverse event.

  2. 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

    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.

Secondary outcomes

  1. 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

    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].

  2. 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

    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].

  3. 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

    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].

  4. Single injection vs. repeated MSCs injection

    Time frame: 12 months: ie the total duration of the trial

    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

  5. Relapse rate

    Time frame: 12 months: ie the total duration of the trial

    Annualized MS-Relapse rate during the 6 months of each treatment cycle, in the three treatment groups.

  6. 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

    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].

  7. 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

    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].

  8. 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

    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].

  9. 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

    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

  10. 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

    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].

  11. 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

    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].

  12. 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

    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]

  13. 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

    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)

  14. 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

    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

  15. 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

    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

Sponsors and collaborators

Lead sponsor

Dimitrios Karussis

Other

Registry information

Official study title

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

Important dates

Study start
2015
Primary completion
2018
Study completion
2018
First posted
Jun 18, 2014
Registry last updated
Aug 1, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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