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

Dimitrios Karussis

Status and phase: Completed; Phase 2

Conditions: Multiple Sclerosis (MS)

Treatments: Biological: Mesenchymal stem cells

Study type: Interventional

Funder types: Other

Identifiers

NCT02166021

MSC-MS-001-IL

Details and patient eligibility

About

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.

Full 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.

Enrollment: 48 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

---

48 participants in 3 patient groups, including a placebo group

IT- Treated

Experimental group

Description:

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.

Treatment:

Biological: Mesenchymal stem cells

IV - Treated

Experimental group

Description:

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.

Treatment:

Biological: Mesenchymal stem cells

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Biological: Mesenchymal stem cells