ParkinStim: Transcranial Direct Current Stimulation for Parkinson's Disease

描述（由申请人提供）：目的是设计、构建和临床评估ParkinStim，这是一种在睡眠期间用于治疗帕金森病（PD）的家庭无创脑极化系统。虽然药物干预和脑深部电刺激（DBS）的当前治疗标准显示出对PD症状的有效治疗，但经颅直流电刺激（tDCS）是一种更便宜且侵入性更小的潜在替代/辅助治疗，副作用很少，可能有助于治疗PD症状，减少药物使用，并减少睡眠障碍。最近的研究表明，应用于初级运动皮层（M1）上方的头皮的非侵入性阳极tDCS可以改善PD症状。tDCS通过无创头皮电极传输的无痛弱电流向大脑皮层提供极化。与其他非侵入性刺激方式不同，例如经颅电刺激（TES）和快速经颅磁刺激（rTMS），这些刺激方式可能会引起疼痛并引起包括癫痫发作和精神病症状在内的副作用，tDCS是无痛的，几乎没有副作用，并且非常适合家庭使用，因为它可以在廉价和紧凑的包装中提供。ParkinStim的主要创新包括1）易于穿戴的可穿戴tDCS硬件，适合家庭使用，2）在睡眠期间提供tDCS的技术，以及3）治疗PD症状和相关睡眠障碍的治疗tDCS系统。拟议的系统将提供一种可穿戴设备，PD患者可以在睡觉前轻松穿戴，并在夜间使用。由于患者通常在前一天的药物作用消失后的早晨感觉最差，因此夜间的刺激可能有助于患者醒来感觉更好。此外，将设备设计为过夜使用将使系统方便和可访问，因此患者无需担心在公共场所或在日常活动中使用该设备。开发将集中在治疗PD的运动症状;然而，所提出的系统可能证明对其他PD症状或相关睡眠障碍有益。对于该I期，我们旨在证明1）通过安全有效地使用现有刺激和电极硬件在睡眠期间向PD患者提供tDCS的技术可行性，以及2）通过证明tDCS降低PD症状严重程度并减少症状波动的临床可行性。10名PD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中睡眠时，将tDCS应用于M1，并收集标准多导睡眠图数据。I期成功标准包括在睡眠期间安全有效地向PD患者施用tDCS，而不会引起觉醒，并证明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tDCS数周的多个夜晚的慢性益处。我们假设I期和II期开发的最终系统将在睡眠期间提供安全有效的tDCS，降低PD症状严重程度，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：帕金森病影响近150万美国人，每年治疗费用接近250亿美元。虽然药物干预和脑深部电刺激（DBS）的当前治疗标准显示了对PD症状的有效治疗，但睡眠期间的经颅直流电刺激（tDCS）是一种成本较低且侵入性较小的潜在替代/辅助治疗，副作用较少，可能有助于治疗PD症状，减少药物使用并减少睡眠障碍。成功的开发将产生一种安全，易于使用的家庭tDCS治疗系统，PD患者可以在夜间使用，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.