Long Term Clinical and Immunological Effects of Repeated Mesenchymal Stem Cells (MSC) Injections in Patients With Progressive Forms 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
- Appearance of adverse events
研究概览
简要总结
An open prospective study with multiple (every 6-12 months) intrathecal or intravenous injections of autologous MSC in patients with progressive forms of MS (secondary progressive, primary progressive or relapsing-progressive), who failed to respond to first and second lines of immunomodulatory treatments and deteriorated (at least 0.5 degree in the EDSS scale) during the year preceding their inclusion to our study or had at least one major relapse without sufficient recovery.
详细描述
An open prospective study with multiple intrathecal or intravenous injections of autologous MSC in 24 patients with progressive forms of MS (secondary progressive, primary progressive or relapsing-progressive), who failed to respond to first and second lines of immunomodulatory treatments and deteriorated (at least 0.5 degree in the EDSS scale) during the year preceding their inclusion to our study or had at least one major relapse without sufficient recovery. Patients will be treated with 1x10 million MSC per kg of body weight, intrathecally and intravenously and subsequently with up to 8 courses of IT- or IV-injections of MSC (at the same dose), at intervals of 6-12 months. The duration of the trial is 4 years.
Patients will be followed up every 3 months for the whole duration of the trial, for safety assessment and changes in the disability scores (EDSS).
Immunological analysis will be performed at 4 time points (day 1, month 1, month 3 and month 6) following the first MSC-treatment and will include a fluorescent cell sorter (FACS) analysis to evaluate the proportions of the lymphocytes expressing markers of immune activation or of regulatory cell phenotype.
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
- •Consenting patients fulfilling the Poser's criteria for definite MS
- •Male and female
- •EDSS rate 5.5-7.5 (moderate to high disability)
- •Failure to two lines of the currently available registered immunomodulatory treatments for MS. The lack of response to these treatments was determined by either an increase in EDSS or the appearance of at least two relapses of MS during the year prior to inclusion.
排除标准
- •Patients who were treated with cytotoxic medications during the last three months prior to the infusion.
- •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 cognitive decline or inability to understand and sign the informed consent.
结局指标
主要结局
Appearance of adverse events
时间窗: 48 months following first treatment
To evaluate the safety and tolerability of MSCs repeated treatment in progressive MS patients
The changes in Expanded Disability Status Scale (EDSS) score 0-10 scale, higher scores show worsening of disability)
时间窗: 48 months
To evaluate the changes in Expanded Disability Status Scale (EDSS) score after repeated MSC treatments compared to run-in period.
次要结局
- Changes in the percentage of CD3+CD69+ cells (activated lymphocytes), following MSC-treatment(up to 6 months)
- Changes in the proliferation ability of mononuclear cells to PHA, following MSC-treatment(up to 6 months)
- Changes in the percentage of CD4/CD25/FoxP3 triple positive stained cells (T regulatory cells), following MSC-treatment(up to 6 months)
- Changes in the percentage of CD11c+/CD86+/Lin- cells (dendritic cells and antigen-presenting macrophages), following MSC-treatment(up to 6 months)