Explorative Trial to Investigate the Safety and Clinical Effects of Autologous Mesenchymal Bone Marrow Stem Cells (MSC) Following Their Intrathecal and Intravenous Administration in Severe Cases of Multiple Sclerosis (MS)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 主要终点
- Safety of one or multiple intrathecaland intravenous injections of autologous MSC in Multiple sclerosis
研究概览
简要总结
Although, effective immunotherapies for MS exist which downregulate the anti-myelin reactivity and reduce the rate of relapses of the disease, there is no effective means today to stop the progression of disability and induce remyelination. Neuronal stem cells were shown to possess the ability to restore neuronal activity and produce new neurons through transdifferentiation. Various other types of stem cells were tested in animal models with promising results, revealing a potential for restoration of the neurological function in neuroimmune and neurodegenerative conditions. Adult bone marrow derived stromal cells (MSC) were shown to induce similar (to neuronal stem cells) immunomodulatory and neuroregenerative effects and were shown in our laboratory to induce neuroprotection in the animal model of chronic experimental autoimmune encephalomyelitis (EAE). MSCs offer practical advantages for clinical therapeutic applications, since they can be obtained from the adult bone marrow and therefore the patient can be the donor for himself, without any danger for rejection of the cells. In addition, MSCs carry a safer profile and are less prone to malignant transformation.
Our initial clinical experience with 10 patients with ALS and 10 with multiple sclerosis show that intravenous and intrathecal administration of MSCs is feasible and safe.
In this study we propose an explorative protocol with the injection of MSCs (both intrathecally and intravenously) in patients with MS, in an effort to prevent further neurodegeneration through neuroprotective mechanisms and induce neuroregeneration and restoration of neuronal function.
The primary endpoint will be to further evaluate the safety and feasibility of the treatment with MSC infusions, in MS patients. Additionally, the migration ability of the transplanted cells will be evaluated by tagging MSCs with the superparamagnetic iron oxide particle (Feridex) for detection by MRI. Clinically the patients will be followed by monthly evaluations of the MS functional rating scale (EDSS) scale. The MRI, will be also used to evaluate changes in the total volume of lesions in the brain and the degree of atrophy.
Significance: This project may provide information for possible therapeutic uses of this type of bone marrow adult stem cells in MS but may also serve as a pilot platform and pave the path for future applications of various types of stem cells in neurodegerative diseases, in general.
详细描述
This study, is designed as a phase 1/2 open-safety clinical trial. At its first phase, 15 consenting patients with MS are included.
Inclusion Criteria:
Consenting patients fulfilled the following 4 inclusion criteria for this study:
- the clinical criteria of Poser et alfor definite MS;
- men and nonpregnant women aged 25 to 65 years;
- duration of disease longer than 5 years; and
- failure to respond to the currently available and registered agents for MS (ie, interferons, glatiramer acetate [Copaxone], and immuno-suppressors), as manifested by an increase of at least 1 degree in the EDSS score during the past year or the appearance of at least 2 major MS relapses during the same period.
Exclusion criteria:
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
- 35 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: 35-65, males and females
- •Duration of disease: >5 years
- •Failure to the currently available -registered- for MS immunomodulatory treatments (ie interferons, Copaxone, immunosuppression): the lack of response to (at least two) of these treatments will be determined/defined by either an increase (deterioration) of at least one degree in the EDSS score during the last year or the appearance of at least two major relapses of MS during the same period of time (under treatment).
- •Exclusion criteria
- •Patients who were treated with cytotoxic medications (cyclophosphamide, Mitoxanthrobne etc) 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
排除标准
- 未提供
结局指标
主要结局
Safety of one or multiple intrathecaland intravenous injections of autologous MSC in Multiple sclerosis
时间窗: One year for the first phase; 4 years for the extension phase
Appearance of adverse events during the 1-4 years of follow up after one or multiple treatments with MSC
次要结局
- Immunological effects of treatment with MSC in MS(1-6 months after the first treatment with MSC)
- Clinical effects in terms of changes in the expended disability status scale (EDSS) at 3-6 month intervals(One year for the first phase; 4 years for the extension phase)
研究者
Dimitrios Karussis
Head of The Center for Multiple Sclerosis & Unit of Neuroimmunology
Hadassah Medical Organization