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

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

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.

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.

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.