A Dose-escalation Safety Trial for Intrathecal Autologous Mesenchymal Stem Cell Therapy in Amyotrophic Lateral Sclerosis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 27
- 试验地点
- 2
- 主要终点
- Number of patients with dose-limiting toxicities
研究概览
简要总结
The purpose of this study is to determine determine the safety of intraspinal delivery of mesenchymal stem cells (MSCs) to the cerebral spinal fluid of patients with Amyotrophic Lateral Sclerosis (ALS) using a dose-escalation study.
详细描述
The primary objective of this study is to determine the safety of intrathecal delivery of autologous mesenchymal stem cells (MSCs) to the cerebrospinal fluid (CSF) of patients with ALS using a dose-escalation study. The trial will include 25 adult, non-ventilator-dependent patients with clinically definite amyotrophic lateral sclerosis (ALS). Cells will be isolated from adipose tissue, expanded ex vivo and then, after ~8 weeks, intrathecal (IT) autologous delivery of MSCs will be performed. There will be 5 treatment groups of up to 5 patients each. Groups 1, 2, and 4 will receive a single dose of cells. Groups 3 and 5 will receive 2 doses of cells separated by 1 month. Groups will be completed sequentially so that patients will not be enrolled into the next treatment group until at least 3 patients in the preceding group have completed the treatment and 1 month of additional observation without significant toxicity. All patients will be followed on a regular basis until death or for a minimum of 2 years after completion of the final infusion. Initial clinical follow-up will be weekly with scheduled blood, CSF and magnetic resonance imaging (MRI) evaluations. After 1 month, patients will have clinical evaluations at 3 month intervals, or earlier if indicated by clinical status.
Addendum: Five subjects from the Group 5 dosing level will received additional injections of MSCs in an extension of the original study, if tolerated.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All patients must have clinically-defined ALS as defined by the World Federation of Neurology criteria
- •Age greater than 18 years
- •If female, must be post-menopausal or had a hysterectomy
- •Permanent resident or citizen of the United States
- •History of a chronic onset of a progressive motor weakness of greater than one year, but less than two years duration
- •Must have vital capacity greater than 65% of predicated for age, gender, and body type
- •Able to comply with protocol requirements, including MRI testing
- •Can provide written informed consent
排除标准
- •Any clinically significant medical condition (e.g., within six months of baseline, had myocardial infarction, angina pectoris, and/or congestive heart failure) that, in the opinion of the investigator, would compromise the safety of patient.
- •Autoimmunity, including Crohn's disease, rheumatoid arthritis, psoriasis
- •Malignancy including melanoma with the exception of localized skin cancers (with no evidence of metastasis, significant invasion, or re-occurrence within three years of baseline). Any other malignancy will not be allowed.
- •Active systemic or local infection near the lumbar puncture site
- •Other active systemic disease as defined by laboratory abnormalities
- •Use of herbal medications or other unapproved drugs
- •Enrolled in an investigational drug trial within 30 days of baseline visit
- •Kokmen Short Test of Mental Status score <32
- •Beck's Depression Inventory score >18
- •Presence of a tracheostomy
- •Ventilator dependent
研究组 & 干预措施
Autologous Mesenchymal Stem Cells
干预措施: autologous mesenchymal stem cells (Biological)
结局指标
主要结局
Number of patients with dose-limiting toxicities
时间窗: baseline -2 years after completion of the final infusion
次要结局
- Number of patients with adverse events(baseline -2 years after completion of the final infusion)
- Change in C-reactive protein levels(baseline, 2 years after completion of the final infusion)
- Change in serum sedimentation rate(baseline, 2 years after completion of the final infusion)
- Change in complete blood counts(baseline, 2 years after completion of the final infusion)
- Change in total nucleated cell count in cerebrospinal fluid (CSF)(baseline, 2 years after completion of the final infusion)
- Change in protein level in cerebrospinal fluid (CSF)(baseline, 2 years after completion of the final infusion)
- Number of patients with presence of cancer cells in their cerebrospinal fluid (CSF)(baseline -2 years after completion of the final infusion)
研究者
Anthony J. Windebank
Principal Investigator
Mayo Clinic