Phase 2 Trial to Investigate the Clinical Efficacy & the Optimal Administration (Based on the Immunological, Clinical & Neuroradiological Effects) of Autologous Mesenchymal Bone Marrow Stem Cells in Active & Progressive Multiple Sclerosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 48
- 试验地点
- 2
- 主要终点
- Safety Assessment
研究概览
简要总结
The purpose of this study is to evaluate the clinical efficacy and the optimal way of administration of autologous mesenchymal bone marrow stem cells (MSC) compering intravenous injection and intrathecal injection vs. placebo, in active-progressive Multiple Sclerosis patients.
详细描述
Mesenchymal stem cells (MSC) induce immune-modulatory and neurotrophic effects and were shown to have an acceptable safety profile for clinical applications. We aimed to evaluate the safety and efficacy of MSC transplantation in active progressive MS and investigate possible neuroprotective effects.
Methods: This single-center double-blind crossover trial enrolled 48 patients with progressive MS (expanded disability status scale (EDSS) range: 3.5-6.5, mean: 5.6+/-0.8). Patients were randomised into three groups and treated intrathecally (IT) or intravenously (IV) with autologous MSCs (1x106/Kg) or placebo. At 6-months, treatment groups were crossed over and patients re-treated with either MSC or placebo. During the 2-months run-in period and the 12-months after treatment, participants were followed using EDSS, 25-foot timed walking, 9-hole peg test, neurocognitive tests, quantitative magnetic resonance imaging (MRI), functional MRI, optic coherence tomography (OCT), visual evoked potentials (VEP), and dynamic visual tests.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Consenting patients fulfilling the Poser's clinical criteria for definite MS
- •Age: 18-65, males and females
- •Duration of disease: >3 years
- •Progressive form of MS: PPMS, SPMS (with/without relapses)
- •EDSS score of 3.5 - 6.5
- •Failure to currently available, registered - first and second line immunomodulatory treatments (at least one).
- •Evidence for new activity of MS during the 3 months before the injection of MSC.
排除标准
- •Patients who were treated with cytotoxic medications during the last 3 months prior to the inclusion.
- •Patients suffering from significant cardiac, renal or hepatic failure or any other disease that may risk the patient or interfere with the ability to interpret the results
- •Patients with active infections
- •Patients with severe cognitive decline or inability to understand and sign the informed consent
- •Patients who received any cellular treatment in the past
研究组 & 干预措施
Placebo
Placebo at the first injection (group 3). After 6 months, 8 patients (group 3A) will be treated with MSC in IT, and 8 additional patients (group 3B) will be treated with MSC in IV.
干预措施: Mesenchymal stem cells (Biological)
IV - Treated
Injection to IV (Group 2). After 6 months, 8 patients (group 2A) will be treated with MSC once again in IV, and 8 additional patients (group 2B) will receive a placebo.
干预措施: Mesenchymal stem cells (Biological)
IT- Treated
Injection to IT (Group 1). After 6 months, 8 patients (group 1A) will be treated with MSC once again in IT, and 8 additional patients (group 1B) will receive a placebo.
干预措施: Mesenchymal stem cells (Biological)
结局指标
主要结局
Safety Assessment
时间窗: 6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group
The proportions of the patients in the three treatment-groups (MSC-IV, MSC-IT and placebo) who experienced any adverse event.
Neurological efficacy
时间窗: 6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group
The proportions of the patients with treatment failure (increase of the EDSS by 1 point for patients with baseline values of 5.0 or less and of 0.5 degree for baseline EDSS of more than 5.0), confirmed by two consecutive evaluations, in the three treatment-groups.
次要结局
- EDSS score(6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group)
- Ambulation score(6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group)
- T2-weighted flair lesions load in MRI(6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group)
- Functional scores(6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group)
- Single injection vs. repeated MSCs injection(12 months: ie the total duration of the trial)
- Gadolinium enhancing lesions in MRI(6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group)
- 25-feet timed walking(6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group)
- 9-hole peg test(6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group)
- Relapse rate(12 months: ie the total duration of the trial)
- Total brain volume in MRI(6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group)
- Functional MRI(6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group)
- Paced Auditory Serial Addition Test (PASAT)(6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group)
- Optical coherence tomography (OCT)(6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group)
- Immunology(6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group)
- Cognitive function: Controlled Oral Word Association Test (COWAT)(6 months for each treatment cycle; the two cycles (each of 6 months duration) will be combined together and provide a single measurement for each group)
研究者
Dimitrios Karussis
Head of The Center for Multiple Sclerosis & Unit of Neuroimmunology
Hadassah Medical Organization