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: 10407653
• 负责人: Jonathan David Charlesworth
• 金额: $ 106.43万
• 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 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10407653
• 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; Hour; Hyperactivity; 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; 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; therapeutically effective; 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.

不宁腿综合症(RLS)影响了超过10%的西方成年人的入睡和睡眠能力 人口。仅在50-79岁的中位年龄组中，就有2500多万成年人正在寻求治疗 RLS，使其成为世界上第二常见的睡眠障碍。RLS的严重腿部感觉最多 在夜间很普遍，从而导致睡眠不足及其下游情绪低落的后果， 易怒、健忘、学习困难、缺乏动力。自愿的腿部运动导致减少 这些症状；然而，这些运动与睡眠不相容。基于药物的RLS疗法得到满足 结果好坏参半，随着时间的推移逐渐变得不那么有效，在许多情况下，还有令人衰弱的一面- 效果。出于这个原因，相当一部分RLS患者转向非标签药物，包括阿片类药物和 苯二氮卓类。存在着对有效的非药物RLS治疗的大量未得到满足的需求。The Noctrix Health 可穿戴式外周神经刺激系统(NPNS)旨在模拟自愿的治疗效果 腿部运动，没有分心的副作用。急性治疗反应的初步开放标签研究显示 NPNS使中、重度RLS患者的RLS症状严重程度降低了83%。设备开发 需要努力将NPNS技术转化为一种紧凑、可穿戴的设备，可以可靠地自我 由患者在家中每日通宵使用。需要临床验证才能确定 关键患者亚群的初步治疗反应。这项SBIR快速通道提案将促进 将这项前景看好的技术转化为可穿戴、易于使用的设备，并评估耐受性， 候选临床亚群的安全性、依从性和治疗反应(药物-幼稚、药物- 难治性和临床医生指导的阿片类药物减少)通过以下目标：第一阶段目标1：设计和 验证最适合日常过夜使用的外形规格。设计一款可穿戴设备，能够提供 程序化治疗波形在必要的持续时间内不间断，其形状因数最小 从现有公司提供的患者和医生反馈中干扰睡眠。目标2：整合 合规跟踪和活动监控。设计和集成3D运动智能传感和活动 正在登录设备。阶段2目标1：建立耐受性、遵从性、安全性，并确定临床亚 群体治疗反应。对3个队列中的每组20名患者进行临床试验(药物-幼稚， 药物难治性和临床医生指导的阿片类药物减少)，以研究耐受性、安全性、依从性和大小 治疗效果。目的2：开发检测RLS相关腿部运动的算法。使用数据 由车载传感器(在阶段1开发并在阶段2目标1收集)提供，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状态标记 症状严重，并最终将用于施加脉冲，以维持睡眠，在必要时。成功 这项临床试验的完成将支持NPNS关键试验的进展和FDA的批准。

项目成果

Adjunctive tonic motor activation enables opioid reduction for refractory restless legs syndrome: a prospective, open-label, single-arm clinical trial.

• DOI: 10.1186/s12883-023-03462-6
• 发表时间: 2023-11-21
• 期刊: BMC NEUROLOGY
• 影响因子: 2.6
• 作者: Buchfuhrer, Mark J.;Roy, Asim;Rodriguez, Stephanye;Charlesworth, Jonathan D.
• 通讯作者: Charlesworth, Jonathan D.