Autologous Mesenchymal Stem Cells for the Treatment of Neuromyelitis Optica Spectrum Disorders

Study Overview
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Brief Summary
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Neuromyelitis optica (NMO) is a demyelinating and degenerative disorder of the central nervous system affecting vision and brain and spinal cord function which leads to accumulating disability with a 5 year-mortality of approximately 30%. Survivors are typically left with severe morbidity secondary to blindness, quadriparesis and respiratory failure. No agent has been found to be highly effective in halting disease activity.Based on recent outcomes of Multipotent mesenchymal stromal cells in autoimmune diseases including multiple sclerosis, and based on the mechanisms of neuromyelitis optica, the investigators anticipate that mesenchymal stem cells transplantation may provide lasting disease stability for neuromyelitis optica patients.

Detailed Description
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Primary objective was to assess feasibility and safety; the investigators compared adverse events from up to 3months before treatment until up to 12 months after the infusion. As a secondary objective, the investigators chose efficacy outcomes to assess the Expanded Disability Status (EDSS)、annual relapse rate (ARR) and time to next relapse after transplant. Third objective anterior visual pathway and pyramidal tract as a model of wider disease. Masked endpoint analyses was used for electrophysiological and selected imaging outcomes.

Official Title
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Autologous Mesenchymal Stem Cells for the Treatment of Progressive and Refractory Neuromyelitis Optica Spectrum Disorders: an Open-label Phase 2a Proof-of-concept Study

Conditions
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Devic's Syndrome, Devic's Neuromyelitis Optica, Devic Syndrome, Devic's Disease, Devic Disease

Intervention / Treatment
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* Biological: Autologous mesenchymal stem cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinically definite neuromyelitis optica or neuromyelitis optica spectrum disorder Age > 18 year EDSS > 3 Progression continued relapses or worsening MRI after at least a year of attempted therapy as evidenced by one or more of the following: Increase of 1 EDSS point (if baseline EDSS<5.0) or 0.5 EDSS points (if baseline EDSS >5.5) Moderate-severe relapses in past 18 months Gadolinium enhancing lesions (double or triple dose Gd) 1 new T2 lesion Evidence of recent inflammatory disease, as evidenced by any one of the following: 1 moderate-severe relapses in past 18 months 1 Gd-enhancing lesions (single, double or triple dose Gd) 1 new T2 lesion Exclusion Criteria: Received Immune inhibitors immunomodulator during the three months before the trial Significant cardiac, renal, or hepatic failure or any other disease that may affect the results of the study Allergies Pregnant or possibly pregnant Cognitive decline to understand or sign the informed consent Brain tumor, HIV (+) tumor marker (+), blood pressure (BP): 200 /110 mmHg Judged not suitable by doctors

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Autologous mesenchymal stem cells group<br>Generated clinical-grade MSC 10 mg chlorpheniramine Po.;100 mg hydrocortisone iv.;10 mg metoclopramide im.;30 min before administration of the cells . MSC a day-case 2·0×106 cells/kg i.v. 15min Infused normal saline 500 Ml over 4 h i.v. | Biological: Autologous mesenchymal stem cells<br>* Autologous mesenchymal stem cells<br>* Other names: MSC;|
| Placebo Comparator: Control group<br>Patients with progressive and refractory NMO treated with regular methods | Biological: Autologous mesenchymal stem cells<br>* Autologous mesenchymal stem cells<br>* Other names: MSC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EDSS | Compare EDSS change before and one year after mesenchymal stem cells (MSC) infusion | change from baseline to one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annual relapse rate | Compare annual relapse rate before and one year after MSC infusion | 1 year after infusion | 
| Lesion load | Compared lesion load before and one year after MSC infusion | 1 year after infusion | 
| Retinal nerve fiber layer (RNFL) | Compared RNFL before and one year after MSC infusion | 1 year after infusion | 
| Cognition | Compare cognition questionnaire scale before and one year after MSC infusion | 1 year after infusion | 
| Immunological assessments | Compare anti-aquaporin4-ab before and one year after MSC infusion. | 1 year after infusion | 
| Immunological assessments | Compare immune cell subpopulation before and one year after MSC infusion. | 1 year after infusion | 
| Immunological assessments | Compare cytokine kinetics before and one year after MSC infusion. | 1 year after infusion | 
| cerebral volume | Compare cerebral volume before and one year after MSC infusion | 1 year after infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autologous mesenchymal stem cells, neuromyelitis optica, treatment