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

Phase 2

Completed

• Conditions: Devic Syndrome; Devic's Disease; Devic's Syndrome; Devic's Neuromyelitis Optica; Devic Disease
• Interventions: Biological: Autologous mesenchymal stem cells

• Registration Number: NCT02249676
• Lead Sponsor: Tianjin Medical University General Hospital

Brief Summary

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

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.

Study Timeline

• Study Start: 2013-01
• Study First Submitted: 2014-09-15
• Study First Submitted QC: 2014-09-22
• Study First Posted: 2014-09-25
• Primary Completion: 2014-12-31
• Study Completion: 2014-12-31
• Status Verified: 2018-10
• Last Update Submitted: 2018-10-15
• Last Update Posted: 2018-10-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Autologous mesenchymal stem cells group	Autologous mesenchymal stem cells	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.
Control group	Autologous mesenchymal stem cells	Patients with progressive and refractory NMO treated with regular methods

Primary Outcome Measures

Name	Time	Method
EDSS	change from baseline to one year	Compare EDSS change before and one year after mesenchymal stem cells (MSC) infusion

Secondary Outcome Measures

Name	Time	Method
Lesion load	1 year after infusion	Compared lesion load before and one year after MSC infusion
Annual relapse rate	1 year after infusion	Compare annual relapse rate before and one year after MSC infusion
Cognition	1 year after infusion	Compare cognition questionnaire scale before and one year after MSC infusion
Immunological assessments	1 year after infusion	Compare cytokine kinetics before and one year after MSC infusion.
Retinal nerve fiber layer (RNFL)	1 year after infusion	Compared RNFL before and one year after MSC infusion
cerebral volume	1 year after infusion	Compare cerebral volume before and one year after MSC infusion

Trial Locations

Locations (1)

Tianjin Medical University General Hospital; 🇨🇳 Tianjin, Tianjin, China