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

Multiple Sclerosis (MS) Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02166021
• Other study ID #: MSC-MS-001-IL
• Status: Completed
• Phase: Phase 2
• Start date: January 29, 2015
• Est. completion date: December 24, 2018

Study information

• Verified date: July 2019
• Source: Hadassah Medical Organization
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: December 24, 2018
• Est. primary completion date: June 15, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis (MS)
• Sclerosis

Intervention

Biological:
• Mesenchymal stem cells
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.

Locations

Country	Name	City	State
Israel	Hadassah Medical Organization	Jerusalem

Sponsors (1)

Lead Sponsor	Collaborator
Dimitrios Karussis

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety Assessment	The proportions of the patients in the three treatment-groups (MSC-IV, MSC-IT and placebo) who experienced any adverse event.	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
Primary	Neurological efficacy	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.	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	EDSS score	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].	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	Ambulation score	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].	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	Functional scores	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].	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	Single injection vs. repeated MSCs injection	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
Secondary	Relapse rate	Annualized MS-Relapse rate during the 6 months of each treatment cycle, in the three treatment groups.	12 months: ie the total duration of the trial
Secondary	T2-weighted flair lesions load in MRI	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].	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	Total brain volume in MRI	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].	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	Gadolinium enhancing lesions in MRI	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].	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	Functional MRI	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
Secondary	25-feet timed walking	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].	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	9-hole peg test	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].	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	Paced Auditory Serial Addition Test (PASAT)	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]	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	Cognitive function: Controlled Oral Word Association Test (COWAT)	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
Secondary	Optical coherence tomography (OCT)	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
Secondary	Immunology	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