Mesenchymal Stem Cells in Multiple Sclerosis (MSCIMS)

Study Overview
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Brief Summary
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Hypothesis: Intravenous administration of bone marrow-derived autologous adult human mesenchymal stem cells is a safe novel therapeutic approach for patients with multiple sclerosis. Mesenchymal Stem Cells in Multiple Sclerosis (MSCIMS) is a phase I/IIA trial designed to establish the safety of intravenous administration of bone marrow-derived autologous adult human mesenchymal stem cells to patients with multiple sclerosis.

Detailed Description
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Disease under investigation: Multiple Sclerosis Phase: I/IIA Number of patients: 10 Design: 18 month cross over, single treatment at 6 months Intervention: Administration of bone marrow-derived autologous mesenchymal stem cells Route of administration: Intravenous Dose: Up to 2,000,000 Mesenchymal Stem Cells per kilogram Source of patients: Referrals accepted from Neurologists in East Anglia and North London, UK Referral Criteria: (all 3 required) Clinically definite multiple sclerosis Expanded Kurtzke Disability Status Score 2.0 - 6.5 (inclusive) Evidence of optic nerve damage by history of optic neuritis, or relative afferent pupillary defect, or optic atrophy on fundoscopy, or abnormal visual evoked potential from either or both eyes suggestive of demyelination Primary Objective: Establish the safety of intravenously administered bone marrow-derived autologous mesenchymal stem cells at a dose of up to 2,000,000 cells/kg over 12 months by monitoring adverse reactions. Secondary Objectives: Explore the efficacy of intravenously administered bone marrow-derived autologous mesenchymal stem cells at a dose of up to 2,000,000 cells/kg over 12 months on visual function by clinical, neurophysiological, and imaging assessments. Outcome Measures: Primary Adverse events Secondary Visual function (acuity and colour) Visual evoked potential latency Optic nerve Magnetisation Transfer Ratio Retinal nerve fibre layer thickness (by optical coherence tomography) Brain lesion Magnetisation Transfer Ratio MRI brain T1 hypointensity load T cell response suppression Tertiary Multiple Sclerosis Functional Composite Score Expanded Kurtzke Disability Status Score

Official Title
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Autologous Adult Human Mesenchymal Stem Cells: a Neuroprotective Therapy for Multiple Sclerosis

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Procedure: MSC Treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinically definite multiple sclerosis Expanded Kurtzke Disability Status Score 2.0 - 6.5 (inclusive) Evidence of optic nerve damage by: history of optic neuritis, or relative afferent pupillary defect, or optic atrophy on fundoscopy, or abnormal visual evoked potential from either or both eyes suggestive of demyelination Prolonged visual evoked potential P100 latency with preserved waveform T2 lesion on MRI optic nerve Retinal nerve fibre layer thickness on optical coherence tomography > 40 microns Exclusion Criteria: Age < 18 years Age > 65 years Patient lacks capacity to give informed consent Presence of a severe bleeding disorder Planning a pregnancy during the trial period Current MS disease modifying therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MSC Treatment<br> | Procedure: MSC Treatment<br>* Intravenous administration of up to 2x10^6 autologous MSCs per kg<br>* Other names: Multipotent Mesenchymal Stromal Cells;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events |  | 0,1,2,3,4,12 and 52 weeks post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual function (acuity and colour) |  | 12 and 52 weeks post treatment | 
| Visual evoked potential latency |  | 12 and 52 weeks post treatment | 
| Optic nerve Magnetisation Transfer Ratio |  | 12 and 52 weeks post treatment | 
| Retinal nerve fibre layer thickness (by optical coherence tomography) |  | 12 and 52 weeks post treatment | 
| Brain lesion Magnetisation Transfer Ratio |  | 12 and 52 weeks post treatment | 
| MRI brain T1 hypointensity load |  | 12 and 52 weeks post treatment | 
| Multiple Sclerosis Functional Composite Score |  | 12 and 52 weeks post treatment | 
| Expanded Kurtzke Disability Status Score |  | 12 and 52 weeks post treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Sclerosis, Safety, Therapeutics, Mesenchymal Stem Cells, Multipotent Mesenchymal Stromal Cells, Optic Neuritis