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.

不宁腿综合征（RLS）影响超过10%的西方成年人入睡和保持睡眠的能力 人口仅在50-79岁的中位年龄组中，就有超过2500万成年人正在寻求治疗， RLS是世界上第二大常见的睡眠障碍。RLS的严重腿部感觉是最 在夜间流行，从而导致睡眠剥夺及其下游后果抑郁情绪， 易怒，健忘，学习困难，缺乏动力。随意的腿部运动会减少 这些症状;然而，这种运动与睡眠不相容。符合基于药物的RLS治疗 结果好坏参半，随着时间的推移逐渐变得不那么有效，并且在许多情况下具有使人衰弱的副作用- 方面的影响.出于这个原因，很大一部分RLS患者转向标签外药物，包括阿片类药物和 苯二氮卓类对于有效的非药物RLS疗法存在大量未满足的需求。夜间健康 可穿戴外周神经刺激系统（NPNS）旨在模拟自愿的治疗益处， 腿部活动而不会产生副作用急性治疗反应的初步开放标签研究显示， NPNS使中度至重度RLS患者的RLS症状严重程度降低了83%。设备开发 需要将NPNS技术转化为一种紧凑的可穿戴设备，这种设备可以可靠地自 由患者在家服用，每天过夜使用。需要进行临床验证，以确定 关键患者亚群的初步治疗反应。这一SBIR快速通道提案将促进 将这一有前途的技术转化为可穿戴的、简单易用的设备，并评估耐受性， 候选临床亚群（未接受过药物治疗、接受过药物治疗、 难治性和临床医生指导的阿片类药物减少）通过以下目的：I期目的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， 程控治疗波形在必要的持续时间内不间断，其形状因子最小 从现有的公司来源的病人和医生的反馈睡眠中断。目标2：整合 合规跟踪和活动监控。设计并集成3D运动智能传感和事件 登录到设备。第2阶段目标1：确定耐受性、依从性、安全性，并确定临床亚组 群体治疗反应。在3个队列（药物初治， 药物难治性和临床医生指导的阿片类药物减量），以研究耐受性、安全性、依从性和 治疗效果目标2：开发用于检测RLS相关腿部运动的算法。使用数据 由机载传感器提供（在第一阶段开发，在第二阶段收集），开发一种算法， 在睡眠期间检测RLS相关的腿部运动。该算法将报告一个客观状态标记， 症状的严重程度，并最终将用于在必要时施加脉冲以维持睡眠。成功 这项临床试验的完成将支持推进到NPNS临床试验和FDA批准。