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

基本信息

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
项目类别：
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

项目摘要

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) 影响超过 10% 的西方成年人入睡和保持睡眠的能力仅在 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。不宁腿综合症，使其成为世界上第二常见的睡眠障碍。不宁腿综合症最严重的腿部感觉。流行于夜间，从而导致睡眠不足及其情绪低落的下游后果，烦躁、健忘、学习困难和缺乏自主的腿部运动会导致腿部运动减少。这些症状；然而，这种运动与基于药物的 RLS 疗法是不相容的。结果好坏参半，随着时间的推移，效果逐渐减弱，并且在许多情况下会产生令人衰弱的副作用出于这个原因，很大一部分 RLS 患者开始使用适应症外药物，包括阿片类药物和药物。对于有效的非药物 RLS 疗法存在大量未满足的需求。可穿戴周围神经刺激系统（NPNS）旨在模仿自愿的治疗效果初步的急性治疗反应开放标签研究表明，腿部运动不会产生分散注意力的副作用。 NPNS 可将中度至重度 RLS 患者的 RLS 症状严重程度降低 83% 设备开发。需要努力将 NPNS 技术转化为紧凑的可穿戴设备，该设备可以可靠地自我需要由患者在家中每天过夜使用来确定。该 SBIR 快速通道提案将促进关键患者亚群的初步治疗反应。将这项有前途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、依从性和对治疗的反应（未接受药物治疗、药物治疗）难治性和临床医生指导的阿片类药物减少），通过以下目标：第一阶段目标 1：设计和验证最适合日常夜间使用的外形尺寸。设计一款可提供以下功能的可穿戴设备。编程治疗波形在必要的持续时间内不间断，且外形尺寸最小目标 2：整合公司现有的患者和医生反馈，从而扰乱睡眠。合规性跟踪和活动监控。设计和集成 3D 运动智能传感和事件。第 2 阶段目标 1：建立耐受性、合规性、安全性并识别临床亚组。进行一项临床试验，分为 3 个队列（未接受过药物治疗、未接受过药物治疗、药物难治性和临床医生指导的阿片类药物减少），以研究阿片类药物的耐受性、安全性、依从性和规模目标 2：开发利用数据检测 RLS 相关腿部运动的算法。由机载传感器（在第一阶段开发并在第二阶段目标 1 中收集）提供，开发算法检测睡眠期间与 RLS 相关的腿部运动，该算法将报告客观状态标记。症状严重程度，并最终在必要时使用脉冲来维持睡眠。该临床试验的完成将支持推进 NPNS 关键试验和 FDA 批准。