A Prospective, Non-randomized, Open Label Study to Assess the Safety and the Efficacy of Autologous Multipotent Mesenchymal Stromal Cells in the Treatment of Amyotrophic Lateral Sclerosis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 26
- 主要终点
- Safety: Complications related to the medicinal product application - new neurological deficit and occurrence of other adverse events
研究概览
简要总结
Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that targets motor neurons. Prognosis is invariably fatal within 3-5 years since manifestation of the disease. Despite improved understanding of the mechanisms underlying ALS, the treatment remains essentially only supportive and focused on symptoms relief. Over the past few years, stem cell research has expanded greatly as a tool for developing new therapies to treat incurable diseases. Stem cell therapy has been shown as promising in several animal ALS models and human clinical trials.
详细描述
Subjects will be assigned to autologous mesenchymal stromal cell (AMSC) treatment according to inclusion and exclusion criteria (see below) screened four times prior to administration. Then the subjects will be observed for three consecutive yearsAfter a half year of screening period, the autologous multipotent mesenchymal stromal cells from bone marrow will be isolated. The cells will be cultivated for 3 passages (3 - 4 weeks) in order to get sufficient amount for therapy, cell suspension for intrathecal application will be prepared and introduced intrathecally through lumbar puncture. Subsequently, all the subjects will be observed at the range of standard medical care used at these types of interventions.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •established diagnosis of definite ALS according to El Escorial criteria
- •riluzole naive or stable dose for at least 2 months,
- •life expectancy more than 2 years
- •patients able to provide written informed consent.
排除标准
- •FVC less than 70%
- •in case of primary bulbar paralysis less than 15 points on Norris bulbar scale,
- •less than 15 points on Norris spinal scale,
- •pregnancy, breastfeeding
- •coagulopathy,
- •skin infection at the site of bone marrow aspiration or application of the cell product,
- •gastrostomy,
- •any significant medical condition that would compromise the safety of the patient (e.g. recent myocardial infarction, congestive heart failure, renal failure, liver failure, cancer, systemic infection, recurrent thromboembolic disease .....),
- •alcohol or drug abuse
- •women of childbearing potential not using effective contraception (established oral contraception, intrauterine device, ligation of the uterine tube) including proven contraceptive measures taken by their sexual partners
- •fertile men not using proven contraceptive measures including effective contraception of their partner (established oral contraception, intrauterine device, ligation of the uterine tube)
研究组 & 干预措施
Autologous Multipotent MSC
Patients with intrathecal administration of Suspension of human autologous MSC 3P in 1.5 ml
干预措施: Suspension of human autologous MSC 3P in 1.5 ml (Biological)
结局指标
主要结局
Safety: Complications related to the medicinal product application - new neurological deficit and occurrence of other adverse events
时间窗: 1 year
Complications at the site of intrathecal infusion of the medicinal product and no new neurological deficit (meningism, paraplegia, urinary incontinence) not attributed to the natural progression of the ALS disease will be recorded at Visits I, III, IV, V, VI, and IX. Occurrence of other potential adverse events, including headache, respiratory failure, leukocytosis, cervical spine stenosis, cystitis and hyperhydrosis will be evaluated on the severity scale (1=mild, 2=moderate, 3=severe). Brain and spinal cord MRI will be performed at Visits I and IX to exclude treatment-related tumor formation, pathological contrast enhancement or other structural pathology.
次要结局
- Efficacy: Inhibition of the disease progression - ALS functional rating scale(18 months)
- Efficacy: Inhibition of the disease progression - Norris scale(18 months)
- Efficacy: Inhibition of the disease progression - Forced vital capacity (FVC)(18 months)