Remotely supervised transcranial direct current stimulation for slowing disease progression in amyotrophic lateral sclerosis (ALS)

远程监督经颅直流电刺激可减缓肌萎缩侧索硬化症 (ALS) 疾病进展

• 批准号: 10217806
• 负责人: Sangeetha Madhavan
• 金额: $ 23.01万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10217806
• 关键词: ALS pathology; Adherence; Adjuvant; Adjuvant Therapy; Affect; Aftercare; Amyotrophic Lateral Sclerosis; Anodes; Biological Markers; Brain; Caregiver research; Caregivers; Caring; Cerebral cortex; Clinic; Clinical; Clinical Management; Clinical Treatment; Control Groups; Development; Diagnosis; Disease; Disease Progression; Effectiveness; Ensure; Environment; Feasibility Studies; Functional disorder; Future; Goals; Home; Human Resources; Impairment; Individual; Intervention; Leg; Longevity; Longitudinal Studies; Lower Extremity; Measures; Motor; Motor Cortex; Motor Neurons; Movement; Muscle; Nerve; Neural Pathways; Neurodegenerative Disorders; Neurologic; Outcome; Participant; Patients; Peripheral Nerve Stimulation; Pharmaceutical Preparations; Plasma; Population; Procedures; Protocols documentation; Quality of life; Questionnaires; Randomized; Rehabilitation therapy; Research; Research Personnel; Riluzole; Risk; Serious Adverse Event; Spinal; Structure; Supervision; Symptoms; Synaptic Transmission; Testing; Therapeutic; Time; Transcranial magnetic stimulation; Transportation; Travel; United States; base; brain-derived growth factor; clinical translation; combat; cost effective; design; follow-up; group intervention; improved; indexing; motor neuron degeneration; motor neuron function; nervous system disorder; neuromechanism; neurophysiology; neuroregulation; neurotransmission; neurotrophic factor; new therapeutic target; noninvasive brain stimulation; novel; novel strategies; peroneal nerve; phenylmethylpyrazolone; portability; preservation; rate of change; recruit; rehabilitation service; remote delivery; repetitive transcranial magnetic stimulation; research facility; safety and feasibility; success; symptom management; telerehabilitation; tibialis anterior muscle; tool

PROJECT SUMMARY ALS affects as many as 30,000 individuals in the United States, with 5,600 new cases diagnosed each year. Riluzole and edaravone, the only drugs approved by the U.S. FDA for ALS, slow ALS progression; however, they do not demonstrate marked improvement in ALS symptoms and increase survival time only by a few months. Hence, most of the care is centered on patient support and symptom management, making rehabilitation an integral aspect for slowing disease progression, prolonging life span and increasing quality of life. Our long-term goal is to develop neuromodulation therapies for easy clinical management of ALS. Transcranial direct current stimulation (tDCS) has been increasingly explored as a promising neuromodulatory tool to prime motor function in several neurological disorders. Despite the emerging importance of cortical dysfunction as a pathophysiological biomarker in disease progression, the study of tDCS in ALS is limited. Here we propose a novel mechanism using remotely supervised tDCS (RS-tDCS) to target hypoexcitable neural pathways to preserve motor function in individuals with ALS. Due to its low risk, ease of use, and portability, tDCS is a candidate neuromodality to be administered in a home-based environment with remote supervision from qualified personnel. Remote supervision would ensure that the stimulation is delivered optimally in the comfort of a patient’s home, reducing burden on patients and caregivers to travel to the clinic or research facility and encourage protocol adherence. We aim to investigate the effectiveness and feasibility of long-term RS-tDCS in individuals with ALS. In a delayed-start design, 38 participants with ALS will be randomized into remotely supervised tDCS or delayed-start control group. The intervention group will receive 24 weeks of anodal tDCS (3 times/week; 72 sessions). The delayed-start group will first receive sham tDCS for 12 weeks followed by a switch to anodal tDCS for 12 weeks. Aim 1 will investigate the safety and feasibility of long-term treatment with anodal RS-tDCS in ALS. Aim 2 will determine the effects of 24-weeks of RS-tDCS on disease progression in individuals with ALS, using the ALS Functional Rating Scale (ALSFRS-R) and other clinical outcomes. As a secondary aim, we will explore the effectiveness of RS-tDCS on upper and lower motor neuron mechanisms in individuals with ALS, quantified using transcranial magnetic stimulation and peripheral nerve stimulation. Successful completion of this project will trigger future studies that will test the clinical translation of tDCS as a home-based neuromodulatory adjuvant to slow disease progression in ALS and create a paradigm shift in the clinical management of ALS.

项目总结 在美国，肌萎缩侧索硬化症患者多达3万人，每年新增诊断病例5600例。 利鲁唑和依达拉奉是美国FDA批准的仅有的治疗ALS的药物，它们减缓了ALS的进展；然而， 它们没有显示出ALS症状的明显改善，只增加了几个人的存活时间 月份。因此，大部分护理都集中在患者支持和症状管理上，使 康复是减缓疾病进展、延长寿命和提高生活质量的不可或缺的方面 生活。我们的长期目标是开发神经调节疗法，使ALS的临床治疗变得容易。 经颅直流电刺激(Tdcs)作为一种很有前途的神经调节疗法越来越受到人们的重视。 在几种神经疾病中启动运动功能的工具。尽管皮质醇的重要性正在显现 功能障碍作为疾病进展的病理生理生物标志物，在ALS中的研究还很有限。 在这里，我们提出了一种新的机制，使用远程监督的tdcs(RS-tdcs)来瞄准低兴奋性 肌萎缩侧索硬化症患者维持运动功能的神经通路。由于它的低风险、易用性和 可携带性，tDCS是一种候选的神经模式，可在基于家庭的环境中使用远程 来自合格人员的监督。远程监控将确保提供刺激 在舒适的患者家中获得最佳体验，减轻患者和护理人员前往诊所或 研究设施，并鼓励遵守协议。我们的目标是调查以下项目的有效性和可行性 肌萎缩侧索硬化症患者的长期RS-tDCs。在延迟启动设计中，38名患有肌萎缩侧索硬化的参与者将 随机分为远程监控tDCS组和延迟启动对照组。干预组将收到 24周阳极TDCs(3次/周；72次)。延迟启动组将首先收到假tdcc 12周后改用阳极式tdcs治疗12周。目标1将调查以下项目的安全性和可行性 肌萎缩侧索硬化症的阳极RS-tDCs长期治疗。目标2将确定24周的RS-tDC对 ALS患者的疾病进展，使用ALSFRS-R和其他 临床结果。作为次要目标，我们将探索RS-tDCS在上下电机上的有效性 ALS患者的神经元机制，用经颅磁刺激和外周神经刺激进行量化 神经刺激。该项目的成功完成将触发未来的研究，这些研究将测试临床 翻译tDCs作为一种基于家庭的神经调节佐剂来减缓ALS的疾病进展并创建 肌萎缩侧索硬化症临床治疗的范式转变。