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

NCT ID: NCT02166021

Last Updated: 2019-08-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-29
• Study Completion Date: 2018-12-24

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.

Conditions

Multiple Sclerosis (MS)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Mesenchymal stem cells

Intervention Type: 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.

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.

Group Type: EXPERIMENTAL

Mesenchymal stem cells

Intervention Type: 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.

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.

Group Type: PLACEBO_COMPARATOR

Mesenchymal stem cells

Intervention Type: 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.

Interventions

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.

Intervention Type: BIOLOGICAL

Other Intervention Names

Autologous MSC

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Dimitrios Karussis

OTHER

Sponsor Role: lead

Responsible Party

Dimitrios Karussis

Head of The Center for Multiple Sclerosis & Unit of Neuroimmunology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Hadas Lemberg, PhD

Role: STUDY_CHAIR

Director, R&D Division

Locations

Hadassah Medical Organization

Jerusalem, , Israel

Countries

Israel

References

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.

Reference Type: DERIVED

PMID: 35641166 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33253391 (View on PubMed)

Other Identifiers

MSC-MS-001-IL

Identifier Type: -

Identifier Source: org_study_id