Noninvasive Peripheral Nerve Stimulation for Restless Legs Syndrome

Study Overview
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Brief Summary
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Prospective multi-site randomized sham-controlled crossover feasibility study evaluating tolerability and efficacy of noninvasive peripheral nerve stimulation (NPNS) for patients with moderate-severe primary Restless Legs Syndrome (RLS). Response to NPNS investigational device was compared to sham control in a 2x2 crossover design such that subjects were assigned to receive 2 weeks of NPNS and 2 weeks of sham, in randomized order.

Official Title
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Chronic Efficacy and Usability of Transcutaneous Electrical Nerve Stimulation in Subjects With Restless Leg Syndrome (RLS)

Conditions
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Restless Legs Syndrome

Intervention / Treatment
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* Device: Noctrix Health NPNS device v1.0 - Active
* Device: Noctrix Health NPNS device v1.0 - Sham


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has moderate-severe RLS symptoms as defined by a score of 15 or greater points on IRLS. RLS symptoms are primarily noticeable in the subject's lower legs and/or feet. Subject reports having a medical diagnosis of primary idiopathic restless legs syndrome (RLS) or Willis-Ekbom Disorder (WED) OR Investigator has diagnosed the subject with primary idiopathic restless legs syndrome (RLS) or Willis-Ekbom Disorder (WED). Subject has experienced RLS symptoms at night on 2 or more nights per week during the previous month. On typical dose and schedule of RLS medication (if any), subject typically experiences RLS symptoms on 2 or more nights per week. RLS symptoms are primarily in the evening and night. Subject owns the necessary equipment to respond to texts, phone calls, and video calls. Subject is 18 years of age or older when written informed consent is obtained. Subject has signed a valid, Institutional Review Board (IRB)-approved informed consent form, can understand the requirements of the study and instructions for device usage, and can converse in English. Exclusion Criteria: Subject has RLS that is known to be caused by another diagnosed condition. Subject has active implantable medical devices anywhere in the body (including pacemakers), or passive medical devices implanted in the leg. Subject has an uncontrolled sleep disorder other than RLS that significantly interferes with their sleep as determined by the trial director or physician. Subject has been diagnosed with one of the following conditions: Epilepsy or other seizure disorder, Cellulitis or open sores of the legs, Renal failure, Iron-Deficiency Anemia, Severe movement disorder symptoms (Parkinson's disease, Huntington's disease, dyskinesia, dystonia), Deep Vein Thrombosis, Stage 4-5 Chronic Kidney Disease, Multiple sclerosis, Current, active or acute or chronic infection other than viral upper respiratory tract infections, A malignancy within the past 5 years (not including basal or squamous cell skin cancer) Subject is on dialysis or anticipated to start dialysis while participating in the study Subject is allergic to electrode gel, polyurethane foam, or lycra. Subject has severe edema in lower legs. Subject has failed a nerve conduction study prescribed by a physician or has been diagnosed with severe peripheral neuropathy. During Visit 1, subject cannot notice the stimulation at the maximal dose or cannot tolerate the stimulation at the minimal effective dose Subject selects Statement 2 or is unable to decide which of the following two statements most closely describe their condition: Statement 1: My symptoms are best characterized by a strong or overwhelming urge to move my legs. Moving my legs often results in temporary relief of that urge. Statement 2: My symptoms are best characterized by involuntary leg spasms that happen at regular intervals. These leg spasms can wake me up in the middle of the night. Subject has significantly changed medication dose or schedule of antidepressants, sleep medications, or RLS medications within the past 30 days. Recent history of alcohol or recreational drug abuse (within the past 6 months). Subject has received an investigational drug or device within the last 30 days or is planning to receive an investigational device during the duration of the study. Subject has undergone a major surgery (excluding dental work) in the previous 30 days. Subject has another medical condition that may affect validity of the study or put the subject at risk as determined by the investigator. Subject is unable or unwilling to comply with study requirements

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Device Feasibility
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Noninvasive Peripheral Nerve Stimulation<br>NPNS device programmed to deliver active stimulation. | Device: Noctrix Health NPNS device v1.0 - Active<br>* Wearable device programmed to deliver electrical stimulation to peripheral nerves of the lower limbs.<br>|
| Sham Comparator: Sham control<br>NPNS device programmed to deliver sham stimulation. | Device: Noctrix Health NPNS device v1.0 - Sham<br>* Wearable device programmed to deliver sham stimulation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the clinical tolerability, usability, and patient response for the prototype device, with the intention of improving overall device performance. | Subject satisfaction and usability questionnaire | Weeks 1-2 of each intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in International Restless Legs Syndrome Study Group Rating Scale (IRLS) score at week 2 | International Restless Legs Syndrome Study Group Rating Scale is a participant-rated questionnaire that rates RLS severity from 0-40, where 40 is the most severe. | Week 2 of each intervention compared to week prior to study entry | 
| Change to Summary NRS score of RLS symptom severity | Participant rating of average RLS symptom severity from 0-10 on a Numerical Rating Scale (NRS) scale, where 10 is the most severe. Participants complete a single Summary NRS scale at the end of each 2-week intervention, rating the average RLS symptoms before, during, and after device usage. | Weeks 1-2 of each intervention | 
| Change to Daily NRS score of RLS symptom severity | Participant rating of average RLS symptom severity from 0-10 on a Numerical Rating Scale (NRS) scale, where 10 is the most severe. Participants complete the Daily NRS scale each day during each 2-week intervention, rating the RLS symptoms before, during, and after the previous night of device use. | Weeks 1-2 of each intervention | 
| Responder rate on CGI-I scale at week 2 relative to baseline | Responder rate is defined as the proportion of responses of Much Improved or Very Much Improved relative to baseline on the 7-point participated-rated Clinical Global Impressions-Improvement (CGI-I) scale. | Week 2 of each intervention compared to week prior to study entry |