Phase 1b Trial of stem cells in ALS

干细胞治疗 ALS 的 1b 期试验

• 批准号: 8994888
• 负责人: NICHOLAS M BOULIS
• 金额: $ 3.65万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-30 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8994888
• 关键词: Address; Adverse event; Alzheimer' s Disease; American; Amyotrophic Lateral Sclerosis; Animals; Autopsy; Bilateral; Brain Diseases; Breathing; Calculi; Cause of Death; Cell Count; Cell Therapy; Cells; Cervical; Cervical spinal cord structure; Cessation of life; Characteristics; Clinical Data; Clinical Trials; Communities; Consensus; Data; Devices; Disease; Dose; Future; Goals; Graft Survival; Growth Factor; Human; Huntington Disease; Injection of therapeutic agent; Life; Lumbar spinal cord structure; Maintenance; Maximum Tolerated Dose; Measures; Miniature Swine; Motor Neurons; Multiple Sclerosis; Muscle; Myography; Nervous System Physiology; Neurodegenerative Disorders; Neuroglia; Neurologic; Neurons; Operative Surgical Procedures; Pain; Parkinson Disease; Pathogenesis; Patients; Phase; Phase II/III Trial; Preparation; Protocols documentation; Quality of life; Research; Research Personnel; Respiratory Diaphragm; Respiratory physiology; Risk; Rodent; Safety; Scheme; Spinal; Spinal Cord; Spinal Cord Diseases; Spinal Muscular Atrophy; Spinal cord injury; Stem cell transplant; Stem cells; Stroke; Testing; Therapeutic; Therapeutic Trials; Time; Transplantation; Treatment Efficacy; Universities; Work; attenuation; cell type; density; design; effective therapy; efficacy testing; efficacy trial; electric impedance; follow-up; high risk; improved; innovation; muscle strength; nervous system disorder; neuroprotection; novel; novel therapeutic intervention; phase 2 study; pre-clinical; prevent; programs; respiratory; safety testing; therapeutic target; trial design

DESCRIPTION (provided by applicant): This proposal outlines a plan for a Phase 1b clinical trial for the injection of human spinal cord derived stem cells (HSSCs) into the cervical spinal cord of patients with ALS. This trial is a follow up to a trial already underway at Emory University, where 12 ALS patients have been injected with the same HSSCs into the lumbar spinal cord. In order to move this therapeutic approach closer to a clinical trial to determine if t is effective in ameliorating disease, we are proposing to test the safety of HSSC injection into the cervical spinal cord. Motor neurons in the cervical spinal cord innervate the respiratory diaphragm, the loss of which is typically the cause of death in ALS patients. We propose that the protection of these neurons is likely to prolong life by preserving respiratory function. This safety trial will employ progressive dose escalation to determine the maximum tolerated dose that can be used for the long term goal of performing Phase 2 and Phase 3 efficacy trials. There are two specific aims. In Aim 1 we propose to sequentially escalate the dose of delivery as defined by 1) the number of cells/injection, 2) the number of injections into the cord, and 3) either unilateral or bilateral injections. This dose escalation scheme is designed to safely and efficiently test our ability to achieve a pre-defined target therapeutic dose, which can be used in the next phase of testing therapeutic efficacy. Aim 2 of this proposal is to examine several exploratory endpoints that may be used to test the efficacy of this therapy in future Phase 2 and Phase 3 trials. These include measures of respiratory function, diaphragm function, muscle strength, and electrical characteristics of muscle (Electrical Impedance Myography). Successful completion of this Phase 1b trial will allow for testing of this highly innovative approach to the treatment of ALS. The impact will extend beyond patients with ALS since this novel trial will provide data on surgical approach and safety, as well as trial design that will be highly relevant to cellular therapeutics for spinal cord injury, multiple sclerosis, spinal muscular atrophies, as well as other neurological diseases.

描述（由申请人提供）：该提案概述了一项 1b 期临床试验计划，该试验将人类脊髓衍生干细胞 (HSSC) 注射到 ALS 患者的颈脊髓中。该试验是埃默里大学正在进行的一项试验的后续试验，该试验已向 12 名 ALS 患者的腰部脊髓注射了相同的 HSSC。为了使这种治疗方法更接近临床试验，以确定是否能有效改善疾病，我们建议测试 HSSC 注射到颈髓中的安全性。颈脊髓中的运动神经元支配呼吸膈肌，呼吸膈肌的丧失通常是 ALS 患者死亡的原因。我们认为，保护这些神经元可能通过保留呼吸功能来延长寿命。该安全性试验将采用渐进剂量递增来确定可用于进行 2 期和 3 期疗效试验的长期目标的最大耐受剂量。有两个具体目标。在目标 1 中，我们建议按顺序递增递送剂量，定义为 1）细胞/注射数量，2）注射到脊髓的数量，以及 3）单侧或双侧注射。这种剂量递增方案旨在安全有效地测试我们达到预定目标治疗剂量的能力，该剂量可用于 下一阶段测试治疗效果。该提案的目标 2 是检查几个探索性终点，这些终点可用于在未来的 2 期和 3 期试验中测试该疗法的疗效。其中包括呼吸功能、膈肌功能、肌肉力量和肌肉电特性（电阻抗肌动描记）的测量。该 1b 期试验的成功完成将有助于测试这种高度创新的 ALS 治疗方法。其影响将不仅仅限于 ALS 患者，因为这项新颖的试验将提供有关手术方法和安全性的数据，以及与脊髓损伤、多发性硬化症、脊髓性肌萎缩症以及其他疾病的细胞疗法高度相关的试验设计。神经系统疾病。