Clinical trial NCT02166021: Clinical Efficacy of Autologous Mesenchymal Bone Marrow Stem Cells in Active & Progressive Multiple Sclerosis
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Sclerosis (MS)
Keywords: Multiple Sclerosis (MS)
Stem Cells
Lead sponsor: Hadassah Medical Organization
Sponsor class: OTHER
First posted: 2014-06-18
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Patients were randomised into three groups and treated intrathecally (IT) or intravenously (IV) with autologous MSCs or placebo. At 6-months, treatment groups were crossed over and patients re-treated with either MSC or placebo
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: Inclusion Criteria:

1. Consenting patients fulfilling the Poser's clinical criteria for definite MS
2. Age: 18-65, males and females
3. Duration of disease: \>3 years
4. Progressive form of MS: PPMS, SPMS (with/without relapses)
5. EDSS score of 3.5 - 6.5
6. Failure to currently available, registered - first and second line immunomodulatory treatments (at least one).
7. Evidence for new activity of MS during the 3 months before the injection of MSC.

Exclusion Criteria:

1. Patients who were treated with cytotoxic medications during the last 3 months prior to the inclusion.
2. 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
3. Patients with active infections
4. Patients with severe cognitive decline or inability to understand and sign the informed consent
5. Patients who received any cellular treatment in the past

Primary outcomes:
measure: Safety Assessment
timeFrame: 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
measure: Neurological efficacy
timeFrame: 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
Secondary outcomes:
measure: EDSS score
timeFrame: 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
measure: Ambulation score
timeFrame: 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
measure: Functional scores
timeFrame: 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
measure: Single injection vs. repeated MSCs injection
timeFrame: 12 months: ie the total duration of the trial
measure: Relapse rate
timeFrame: 12 months: ie the total duration of the trial
measure: T2-weighted flair lesions load in MRI
timeFrame: 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
measure: Total brain volume in MRI
timeFrame: 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
measure: Gadolinium enhancing lesions in MRI
timeFrame: 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
measure: Functional MRI
timeFrame: 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
measure: 25-feet timed walking
timeFrame: 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
measure: 9-hole peg test
timeFrame: 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
measure: Paced Auditory Serial Addition Test (PASAT)
timeFrame: 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
measure: Cognitive function: Controlled Oral Word Association Test (COWAT)
timeFrame: 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
measure: Optical coherence tomography (OCT)
timeFrame: 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
measure: Immunology
timeFrame: 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
Other outcomes:
Locations:
city: Jerusalem
country: Israel
facility: Hadassah Medical Organization
Study officials:
affiliation: Director, R&D Division
name: Hadas Lemberg, PhD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.