ParkinStim: Transcranial Direct Current Stimulation for Parkinson's Disease

描述(申请人提供)：目标是设计、建造和临床评估帕金森氏症，这是一种在睡眠期间用于治疗帕金森氏病(PD)的基于家庭的非侵入性大脑极化系统。虽然目前药物干预和脑深部刺激(DBS)的治疗标准显示出对PD症状的有效治疗，但经颅直流电刺激(TDC)是一种成本更低、侵入性更小的潜在替代/辅助治疗方法，副作用很少，可能有助于治疗PD症状、减少药物使用和减少睡眠障碍。最近的研究表明，在初级运动皮质(M1)上方的头皮上应用非侵入性阳极TDC可以改善帕金森病症状。TDC通过非侵入性头皮电极传递的无痛微弱电流向大脑皮层提供极化。与其他非侵入性刺激方式，如经颅电刺激(TES)和快速经颅磁刺激(RTMS)，可能会导致疼痛和副作用，包括癫痫发作和精神症状，tDCS是无痛的，几乎没有副作用，是家庭使用的理想选择，因为它可以以廉价和紧凑的包装提供。帕金斯蒂姆公司的主要创新包括1)适合家庭使用的易于佩戴的可穿戴tDCS硬件，2)在睡眠期间提供tDCS的技术，以及3)治疗帕金森病症状和相关睡眠障碍的治疗性tDCS系统。拟议中的系统将提供一种可穿戴设备，帕金森氏症患者可以在入睡前轻松佩戴，并通宵使用。由于患者通常在前一天的药物用完后第二天早上感觉最差，所以夜间的刺激可能会帮助患者醒来时感觉更好。此外，将该设备设计为夜间使用将使该系统变得方便和可访问，因此患者不必担心在公共场合或日常活动中使用该设备。开发的重点将是治疗帕金森病的运动症状；然而，拟议的系统可能会被证明对其他帕金森病症状或相关的睡眠障碍有利。在这一阶段，我们的目标是：1)通过安全有效地利用现有刺激和电极硬件向帕金森病患者提供睡眠中的tDCs，从而证明技术上的可行性；2)通过证明tDCs降低帕金森病症状的严重性和减少症状波动，证明临床上的可行性。10名帕金森病受试者将参加一项平衡交叉临床研究，在此期间，当受试者在睡眠实验室睡觉时，对M1应用tDCS，并收集标准的多导睡眠图数据。第一阶段的成功标准包括在睡眠期间安全有效地给帕金森病患者使用tdcs，而不会导致醒来，并显示出tdcs的急性治疗效果。虽然第一阶段旨在评估tdcs的急性益处，但第二阶段将调查在家中使用多个晚上tdcs在几周内的长期益处。我们假设，第一阶段和第二阶段开发的最终系统将在睡眠期间提供安全有效的tDCs，降低PD症状的严重性，最大限度地减少运动波动，减少所需药物，并改善睡眠质量。 公共卫生相关性：帕金森氏症影响着近150万美国人，每年的治疗费用接近250亿美元。虽然目前药物干预和脑深部刺激(DBS)的治疗标准显示出对PD症状的有效治疗，但睡眠期间经颅直流电刺激(TDC)是一种成本更低、侵入性更小的潜在替代/辅助治疗方法，副作用很少，可能有助于治疗PD症状、减少药物使用和减少睡眠障碍。成功的开发将带来一种安全、易于使用的基于家庭的tdcs治疗系统，帕金森病患者可以在夜间使用，以便在白天感觉更好。

DESCRIPTION (provided by applicant): The objective is to design, build, and clinically assess ParkinStim", a home-based, noninvasive brain polarization system used during sleep to treat Parkinson's disease (PD). While current therapeutic standards of drug intervention and deep brain stimulation (DBS) show effective treatment of PD symptoms, transcranial direct current stimulation (tDCS) is a less expensive and less invasive potential alternative/adjunct treatment with few side effects that may help treat PD symptoms, decrease medication usage, and reduce sleep disturbances. Recent studies have demonstrated that noninvasive anodal tDCS applied to the scalp over primary motor cortex (M1) can improve PD symptoms. tDCS provides polarization to the cerebral cortex via painless weak currents transmitted through noninvasive scalp electrodes. Unlike other noninvasive stimulation modalities such as transcranial electrical stimulation (TES) and rapid transcranial magnetic stimulation (rTMS) that can be painful and cause side effects including seizures and psychotic symptoms, tDCS is painless, poses few side effects, and is ideal for home use since it can be provided in an inexpensive and compact package. The primary innovations of ParkinStim include 1) easy-to-don wearable tDCS hardware suitable for home use, 2) a technique for providing tDCS during sleep, and 3) a therapeutic tDCS system to treat PD symptoms and related sleep disturbances. The proposed system will provide a wearable device that patients with PD can easily don before going to sleep and use through the night. Since patients often feel worst in the morning after medication from the previous day has worn off, stimulation during the night may help patients wake up feeling better. Additionally, designing the device for overnight use will make the system convenient and accessible so patients need not worry about using the device in public or during their daily activities. Development will focus on treating the motor symptoms of PD; however, the proposed system may prove beneficial for other PD symptoms or related sleep disturbances. For this Phase I, we aim to demonstrate 1) technical feasibility by safely and effectively using existing stimulation and electrode hardware to provide tDCS to PD patients during sleep and 2) clinical feasibility by demonstrating that tDCS reduces PD symptom severities and decreases symptom fluctuations. Ten PD subjects will participate in a counterbalanced crossover clinical study during which tDCS is applied to M1 while the subject sleeps in a sleep laboratory and standard polysomnography data is collected. Phase I success criteria include safely and effectively administering tDCS to PD patients during sleep without causing waking and demonstrating an acute therapeutic effect of tDCS. While Phase I is designed to evaluate the acute benefits of tDCS, Phase II will investigate the chronic benefits of multiple nights of tDCS used in the home over several weeks. We hypothesize that the final system resulting from Phase I and II development will provide safe and effective tDCS during sleep, decrease PD symptom severities, minimize motor fluctuations, reduce required medication, and improve sleep quality. PUBLIC HEALTH RELEVANCE: Parkinson's disease affects nearly 1.5 million Americans with annual treatment costs approaching $25 billion. While current therapeutic standards of drug intervention and deep brain stimulation (DBS) show effective treatment of PD symptoms, transcranial direct current stimulation (tDCS) during sleep is a less expensive and less invasive potential alternative/adjunct treatment with few side effects that may help treat PD symptoms, decrease medication usage, and reduce sleep disturbances. Successful development will result in a safe, easy-to-use home-based tDCS therapy system PD patients can use during the night to feel better during the day.