Noninvasive Peripheral Nerve Stimulation for Restless Legs Syndrome During Opioid Medication Reduction

Study Overview
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Brief Summary
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Prospective open-label single-arm feasibility study assessing the tolerability of opioid medication reduction in conjunction with noninvasive peripheral nerve stimulation (NPNS) for patients taking prescription opioids to treat moderate-severe primary RLS.

Detailed Description
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For RLS patients taking a stable dose of prescription opioid medications prior to study entry, iterative opioid dose reduction is performed in conjunction with open-label NPNS treatment. For each of two iterative step-downs in opioid dose (step-down #1 and step-down #2), a 1-2-week run-in phase to allow resolution of opioid withdrawal symptoms unrelated to RLS is followed by a 1-wk assessment phase to evaluate if RLS symptoms have increased. Study participation is terminated if there is a clinically significant increase in RLS severity during the assessment phase or if there are intolerable opioid withdrawal symptoms at any time. Participants who tolerate both step-downs have the option of an extension phase involving a third step-down with the same format.

Official Title
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Exploratory Study Assessing the Response of Restless Legs Syndrome (RLS) Patients to Non-invasive Peripheral Nerve Stimulation (NPNS) During Opioid Medication Reduction

Conditions
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Restless Legs Syndrome

Intervention / Treatment
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* Device: Noninvasive Peripheral Nerve Stimulation (NPNS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has received a medical diagnosis of primary restless legs syndrome (RLS) Subject is currently taking a stable dose of at least one prescription opioid for RLS, where the total opioid dose is less than or equal to 60mg morphine milligram equivalents (MME) per day. RLS symptoms are most significant in the subject's legs and/or feet. Subject possesses the necessary equipment, internet/phone accessibility, and communication ability to complete electronic questionnaires and respond to electronic communications and phone calls from the research staff throughout the in-home portion of the study. Subject is 18 to 89 years of age (inclusive) 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. Subject has been taking a stable dose and schedule of prescription opioids for RLS for at least 3 months prior to enrollment. Exclusion Criteria: Subject has RLS that is known to be caused by another diagnosed condition (i.e. secondary RLS). Subject was misdiagnosed with RLS, as determined by the investigator (e.g. actual diagnosis of Periodic Leg Movement Disorder (PLMD), arthritis, leg spasms or neuropathy without comorbid RLS). Subject has primary sleep disorder other than RLS that significantly interferes with sleep at the present time (e.g. unmanaged sleep apnea or general insomnia). Subject has been diagnosed with one of the following conditions at any time: Epilepsy or other seizure disorder, Severe movement disorder symptoms (Parkinson's disease, Huntington's disease, dyskinesia, dystonia), Deep Vein Thrombosis, Multiple sclerosis Subject has an active diagnosis of one of the following conditions: Acute or chronic infection other than viral upper respiratory tract infections, Stage 4-5 chronic kidney disease or renal failure, Iron-deficient anemia, Severe edema affecting lower legs Subject has any of the following at the location of device application: Acute injury, Cellulitis, Open sores Subject has 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 has severe peripheral neuropathy affecting the lower legs and/or subject has neuropathy and is unable to clearly distinguish between symptoms of neuropathy and symptoms of RLS. During NPNS calibration, subject has a sensation threshold above the upper-cutoff value (e.g. 30mA), the subject finds stimulation intensities less than 15 mA to be uncomfortable or distracting, or the device does not properly fit the subject. Subject has significantly changed dose or schedule of a medication that may impact RLS symptoms within the 30 days prior to enrollment, as judged by the investigator (e.g. antidepressants, sleep medications, sedative antihistamines). 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 another medical condition that may affect validity of the study as determined by the investigator. Subject is unable or unwilling to comply with study requirements. Moderate or severe cognitive disorder or mental illness. Subject has prior experience with Noctrix Health NPNS devices. Subject has active implantable medical devices anywhere in the body (including pacemakers), or metal implant at the site of study device electrode application. Subject has known allergy to electrode gel, polyurethane foam, or lycra. Subject is pregnant or trying to become pregnant. Subject has undergone a major surgery (excluding dental work) in the previous 30 days. Subject has another medical condition that may put the subject at risk as determined by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 89 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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Noninvasive Peripheral Nerve Stimulation (NPNS)<br>NPNS device programmed to deliver active stimulation. | Device: Noninvasive Peripheral Nerve Stimulation (NPNS)<br>* NPNS device programmed to deliver active stimulation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Opioid reduction tolerability rate during step-down #1 as measured by Clinical Global Impression - Improvement (CGI-I) scale | Percentage of subjects without a clinically significant increase in RLS symptoms (i.e. CGI-I score of 5 or less relative to baseline) during the first Phase involving an opioid dose reduction of >= 20% relative to baseline. | 1 week assessment period for step-down #1 compared to 1 week baseline period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Opioid reduction tolerability rate during step-down #2 as measured by Clinical Global Impression - Improvement (CGI-I) scale | Percentage of subjects without a clinically significant increase in RLS symptoms (i.e. CGI-I score of 5 or less relative to baseline) during the first Phase involving an opioid dose reduction of >= 1/3 relative to baseline | 1 week assessment period for step-down #2 compared to 1 week baseline period | 
| Change from baseline in International Restless Legs Syndrome Study Group Rating Scale (IRLS) score during step-down #1 | IRLS is a participant-rated questionnaire that rates RLS severity from 0-40, where 40 is the most severe. | 1 week assessment period for step-down #1 compared to 1 week baseline period | 
| Change from baseline in IRLS score during step-down #2 | IRLS is a participant-rated questionnaire that rates RLS severity from 0-40, where 40 is the most severe. | 1 week assessment period for step-down #2 compared to 1 week baseline period | 
| Maximal tolerated reduction in opioid dose | Maximal percentage reduction in opioid dose relative to baseline associated with a CGI-I score of 5 or less, averaged across subjects. | Time Frame: 1 week assessment period for final step-down compared to 1 week baseline period |