Autologous Mesenchymal Stem Cells for the Treatment of Progressive and Refractory Neuromyelitis Optica Spectrum Disorders: an Open-label Phase 2a Proof-of-concept Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- EDSS
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Autologous mesenchymal stem cells (Biological)
Control group
Patients with progressive and refractory NMO treated with regular methods
干预措施: Autologous mesenchymal stem cells (Biological)
结局指标
主要结局
EDSS
时间窗: change from baseline to one year
Compare EDSS change before and one year after mesenchymal stem cells (MSC) infusion
次要结局
- Lesion load(1 year after infusion)
- Annual relapse rate(1 year after infusion)
- Cognition(1 year after infusion)
- Retinal nerve fiber layer (RNFL)(1 year after infusion)
- cerebral volume(1 year after infusion)
- Immunological assessments(1 year after infusion)
研究者
Fu-Dong Shi
Head of Neurology Department
Tianjin Medical University General Hospital