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

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

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.

Study Overview

• Status: Completed
• Conditions: Devic's Disease; Devic's Syndrome; Devic's Neuromyelitis Optica; Devic Syndrome; Devic Disease
• Intervention / Treatment: Biological: Autologous mesenchymal stem cells

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 Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300052
      • Tianjin Medical University General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Autologous mesenchymal stem cells group; 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; Autologous mesenchymal stem cells; Other Names: MSC
PLACEBO_COMPARATOR: Control group; Patients with progressive and refractory NMO treated with regular methods	Biological: Autologous mesenchymal stem cells; Autologous mesenchymal stem cells; Other Names: MSC

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Tianjin Medical University General Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2013
• Primary Completion (ACTUAL): December 31, 2014
• Study Completion (ACTUAL): December 31, 2014

Study Registration Dates

• First Submitted: September 15, 2014
• First Submitted That Met QC Criteria: September 22, 2014
• First Posted (ESTIMATE): September 25, 2014

Study Record Updates

• Last Update Posted (ACTUAL): October 17, 2018
• Last Update Submitted That Met QC Criteria: October 15, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: treatment; neuromyelitis optica; Autologous mesenchymal stem cells
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Eye Diseases; Disease; Optic Nerve Diseases; Cranial Nerve Diseases; Myelitis, Transverse; Optic Neuritis; Syndrome; Neuromyelitis Optica
• Other Study ID Numbers: IRB2013-055-02