Treatment of Restless Legs Syndrome through non-invasive peripheral nerve stimulation

通过无创周围神经刺激治疗不宁腿综合症

• 批准号: 10010174
• 负责人: Jonathan David Charlesworth
• 金额: $ 46.15万
• 依托单位: NOCTRIX HEALTH, INC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2021-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10010174
• 关键词: 3-Dimensional; Acceleration; Accelerometer; Acute; Adult; Adverse event; Affect; Algorithms; Benzodiazepines; Brain; Centers for Disease Control and Prevention (U.S.); Clinical; Clinical Trials; Data; Depressed mood; Detection; Device or Instrument Development; Devices; Dose; Electrodes; Electromyography; Epidemic; Esthesia; Event; FDA approved; Feedback; Frequencies; Goals; Health; Home environment; Hour; Hyperactive behavior; Immobilization; Knee; Lead; Learning; Leg; Legal patent; Length; Life; Measurement; Medicare claim; Memory; Monitor; Motion; Motivation; Movement; Nerve Fibers; Numeric Rating Scale; Opioid; Output; Participant; Patients; Peripheral Nerve Stimulation; Pharmaceutical Preparations; Phase; Physicians; Physiologic pulse; Polysomnography; Population; Prevalence; Public Health; Quality of life; Refractory; Reporting; Restless Legs Syndrome; Safety; Schedule; Self Administration; Sensory; Severities; Side; Signal Transduction; Sleep; Sleep Deprivation; Sleep Disorders; Small Business Innovation Research Grant; Source; Symptoms; System; Technology; Testing; Therapeutic; Time; Translating; Translations; Treatment Efficacy; United States; Validation; Weight; Width; Withdrawal; Work; age group; base; clinical candidate; cohort; commercialization; control theory; design; falls; impression; improved; non-drug; novel therapeutics; off-label drug; off-label use; open label; patient subsets; prescription opioid; reduce symptoms; sensor; side effect; sleep onset; sleep quality; treatment effect; treatment response; usability; wearable device

Restless Legs Syndrome (RLS) affects the ability to fall and stay asleep for more than 10% of the western adult population. In the median age group of 50-79 years alone, more than 25 million adults are seeking treatment for RLS, making it the second most common sleep disorder in the world. The severe leg sensations of RLS are most prevalent at night, thus leading to sleep deprivation and its downstream consequences of depressed mood, irritability, forgetfulness, difficulty learning, and lack of motivation. Voluntary leg movements lead to reduction in these symptoms; however, such movements are incompatible with sleep. Drug-based RLS therapies are met with mixed results, becoming progressively less effective over time, and in many cases having debilitating side- effects. For this reason, a significant portion of RLS patients move to off-label medications, including opiates and benzodiazepines. There exists a large unmet need for an effective non-drug RLS therapy. The Noctrix Health wearable Peripheral Nerve Stimulation System (NPNS) is designed to mimic the therapeutic benefits of voluntary leg movements without the distracting side-effects. Initial open-label studies of acute therapeutic response show that NPNS reduces RLS symptom severity by 83% in moderate to severe RLS patients. Device development work is required to translate the NPNS technology into a compact, wearable device that can be reliably self- administered by patients in the home for daily overnight use. Clinical validation is required to determine preliminary therapeutic response in key patient sub-populations. This SBIR Fast Track proposal will facilitate the translation of this promising technology into a wearable, simple-to-use device and evaluate tolerability, safety, compliance, and response to treatment for candidate clinical sub-populations (drug-naïve, drug- refractory, and clinician-guided opiate-reduction) through the following Aims: Phase I Aim 1: Design and validate form factor most compatible for daily overnight use. Design a wearable device that can deliver the programmed therapy waveform uninterrupted for the requisite duration with a form factor that is minimally disruptive to sleep from existing company-sourced patient and physician feedback. Aim 2: Integrate compliance tracking and activity monitoring. Design and integrate 3D motion smart sensing and event logging into the device. Phase 2 Aim 1: Establish tolerability, compliance, safety, and identify clinical sub- population therapeutic response. Conduct a clinical trial with 20 patients in each of 3 cohorts (drug-naïve, drug-refractory, and clinician-guided opiate-reduction) to study tolerability, safety, compliance, and size of treatment effect. Aim 2: Develop algorithm for detection of RLS-related leg movements. Using the data provided by on-board sensors (developed in Phase 1 and collected in Phase II Aim 1), develop an algorithm for detection of RLS-related leg movements during sleep. The algorithm will report an objective state marker of symptom severity and will ultimately be used to apply pulses to maintain sleep, when necessary. Successful completion of this clinical trial will support advancement to an NPNS Pivotal trial and FDA approval.

不安的腿综合征（RLS）会影响跌倒和入睡的能力超过10％的西方成人 人口。仅在50 - 79年的中位年龄组中，超过2500万成年人正在寻求治疗 RLS，使其成为世界第二常见的睡眠障碍。 RLS的严重腿部感觉是 晚上普遍存在，从而导致睡眠不足及其在情绪低落的下游后果， 烦躁，健忘，艰难的学习和缺乏动力。自愿运动导致减少 这些症状；但是，这种运动与睡眠不相容。满足基于药物的RLS疗法 随着时间的流逝而变得越来越降低结果，并且在许多情况下都使人衰弱 - 效果。因此，很大一部分RLS患者转移到标签外药物外，包括阿片类药物和 苯二氮卓。对有效的非药物RLS疗法存在很大的未满足需求。 Noctrix健康 可穿戴外围神经刺激系统（NPN）旨在模仿自愿的治疗益处 腿部运动没有分散注意力的副作用。急性治疗反应的初步开放标签研究表明 在中度至重度RLS患者中，NPN将RLS症状严重程度降低了83％。设备开发 需要工作才能将NPNS技术转化为紧凑的可穿戴设备，这可以是可靠的自我 由家中的患者管理，每天过夜。需要临床验证以确定 关键患者亚群的初步治疗反应。这个SBIR快速提案将准备 将这种承诺技术转换为可穿戴，易于使用的设备并评估耐受性， 安全，依从性和对候选临床亚群治疗的治疗（药物，药物 - 通过以下目的来难治性和临床引导优化减少）：第一阶段目标1：设计和设计和 验证外形最适合每天隔夜使用。设计可穿戴设备，可以输送 编程治疗波形在必要的持续时间内不间断，形式最小 破坏了现有公司为患者和身体反馈的睡眠。目标2：集成 合规性跟踪和活动监控。设计和集成的3D运动智能传感和事件 登录设备。第2阶段目标1：建立耐受性，合规性，安全性，并确定临床子 - 人口治疗反应。在3个队列中的每一个中，对20例患者进行临床试验（药物， 药物难治性和临床引导优化还原）研究可耐受性，安全性，合规性和大小 治疗效果。 AIM 2：开发用于检测与RLS相关的腿部运动的算法。使用数据 由车载传感器提供（在第1阶段开发并在II阶段AIM 1中收集），开发一种算法 在睡眠期间检测与RLS相关的腿部运动。该算法将报告一个客观的状态标记 症状严重程度，最终将在必要时使用脉冲来维持睡眠。成功的 该临床试验的完成将支持NPNS关键试验和FDA批准的进步。