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

项目摘要 在美国，ALS影响多达30，000人，每年诊断出5，600例新病例。 阿舒唑和依达拉奉是美国FDA批准的唯一用于ALS的药物，它们减缓了ALS的进展;然而， 它们并没有表现出ALS症状的显著改善， 个月因此，大部分护理都集中在患者支持和症状管理上， 康复是减缓疾病进展、延长寿命和提高生活质量的一个组成部分。 生活我们的长期目标是开发神经调节疗法，以便于ALS的临床管理。 经颅直流电刺激（Transcranial direct current stimulation，tDCS）作为一种很有前途的神经调节剂，已被越来越多地研究。 在几种神经系统疾病中启动运动功能的工具。尽管大脑皮层的重要性日益显现， 尽管tDCS功能障碍作为疾病进展中的病理生理学生物标志物，但ALS中tDCS的研究有限。 在这里，我们提出了一种新的机制，使用远程监督tDCS（RS-tDCS），以目标hypoexcitable 神经通路来保护ALS患者的运动功能。由于其风险低，易于使用， 便携性，tDCS是一种候选的神经模态管理在家庭为基础的环境与远程 合格人员的监督。远程监控将确保刺激被传递 最佳地在患者的家中舒适地进行，减少患者和护理人员前往诊所的负担， 研究设施，并鼓励遵守协议。我们的目的是研究的有效性和可行性， ALS患者的长期RS-tDCS。在延迟开始设计中，将有38名ALS参与者 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周的阳极tDCS（3次/周; 72次）。延迟开始组将首先接受假tDCS， 12周后转为阳极tDCS 12周。目的1将研究以下方法的安全性和可行性： 在ALS中使用阳极RS-tDCS进行长期治疗。目标2将确定24周RS-tDCS对 ALS患者的疾病进展，使用ALS功能评定量表（ALSFRS-R）和其他 临床结果。作为次要目标，我们将探索RS-tDCS对上下电机的有效性 ALS患者的神经元机制，使用经颅磁刺激和外周 神经刺激该项目的成功完成将引发未来的研究，将测试临床 将tDCS转化为家庭神经调节佐剂，以减缓ALS的疾病进展， ALS临床管理的范式转变。

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.