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.
Public Health Relevance Statement: Restless Legs Syndrome, characterized by uncomfortable and often severe leg sensations especially at night, affects more than one in ten adults in the United States, contributing to the widespread prevalence of sleep disorders in what the Centers for Disease Control have declared a public health epidemic. Drug and device- based RLS therapies have met with mixed results, with no new therapies approved by the FDA in more than 5 years, and with a significant portion of RLS patients compelled to move to off-label medications, including opiates. In this proposal, we further develop and clinically test the tolerability, safety, compliance, and therapeutic response of our non-drug non-invasive Peripheral Nerve Stimulation System; providing RLS relief by simulating leg movement through neurostimulation without disrupting the ability to fall and stay asleep.
Project Terms: 3-Dimensional; Acceleration; Accelerometer; Acute; Adult; Adverse event; Affect; age group; Algorithms; base; Benzodiazepines; Brain; Centers for Disease Control and Prevention (U.S.); Clinical; clinical candidate; Clinical Trials; cohort; commercialization; control theory; Data; Depressed mood; design; Detection; Device or Instrument Development; Devices; Dose; Electrodes; Electromyography; Epidemic; Esthesia; Event; falls; FDA approved; Feedback; Frequencies; Goals; Health; Home environment; Hour; Hyperactive behavior; Immobilization; impression; improved; Knee; Lead; Learning; Leg; Legal patent; Length; Life; Measurement; Medicare claim; Memory; Monitor; Motion; Motivation; Movement; Nerve Fibers; non-drug; novel therapeutics; Numeric Rating Scale; off-label drug; off-label use; open label; Opioid; Output; Participant; patient subsets; Patients; Peripheral Nerve Stimulation; Pharmaceutical Preparations; Phase; Physicians; Physiologic pulse; Polysomnography; Population; prescription opioid; Prevalence; Public Health; Quality of life; reduce symptoms; Refractory; Reporting; Restless Legs Syndrome; Safety; Schedule; Self Administration; sensor; Sensory; Severities; Side; side effect; Signal Transduction; Sleep; Sleep Deprivation; Sleep Disorders; sleep onset; sleep quality; Small Business Innovation Research Grant; Source; Symptoms; System; Technology; Testing; Therapeutic; Time; Translating; Translations; treatment effect; Treatment Efficacy; treatment response; United States; usability; Validation; wearable device; Weight; Width; Withdrawal; Work
