Noninvasive Peripheral Nerve Stimulation for Medication-Naive and Medication-Refractory RLS

Inclusion Criteria:

1. Subject has received a medical diagnosis of primary restless legs syndrome (RLS).
2. Subject is either medication-naïve or medication-refractory.
3. Subject has moderate-severe RLS symptoms as defined by a score of 15 or greater pointson IRLS (International Restless Legs Syndrome Study Group Rating Scale) over the weekprior to study entry.
4. RLS symptoms interfered with sleep on at least 3 nights per week during the monthprior to study entry.
5. RLS symptoms are most significant in the subject's lower legs and/or feet.
6. RLS symptoms are most significant after 6pm.
7. Subject agrees to not change dosage or schedule of any medications that are known toimpact RLS symptoms during the study, including RLS medications, antidepressants,sleep medications, or sedative antihistamines.
8. Subject agrees to not make major lifestyle changes during the study that wouldsignificantly affect bedtime, such as major changes to diet, exercise, or career.
9. Subject possesses the necessary equipment, internet/phone accessibility, andcommunication ability to complete electronic questionnaires and respond to electroniccommunications and phone calls from the research staff throughout the in-home portionof the study.
10. Subject is ≥ 22 and ≤ 89 years of age when written informed consent is obtained.
11. Subject has signed a valid, IRB-approved informed consent form, can understand therequirements of the study and instructions for device usage, and can converse inEnglish.

Exclusion Criteria:

1. Subject has RLS that is known to be caused by another diagnosed condition (i.e.secondary RLS).
2. Subject is taking an unstable or inconsistent dose or schedule of medication that islikely to impact RLS symptoms, such as antidepressants, sleep medications, or sedativeantihistamines or has changed dosage within the past 30 days.
3. Subject has changed dose and schedule of RLS medications within the month prior tostudy entry or is otherwise on an inconsistent dose or schedule of RLS medications.
4. Subject has prior experience with Noctrix Health NPNS devices.
5. Subject was misdiagnosed with RLS, as determined by the investigator (e.g. actualdiagnosis of PLMD, arthritis, leg spasms or neuropathy without comorbid RLS).
6. Subject has a primary sleep disorder other than RLS that significantly interferes withsleep at the present time (e.g. obstructive sleep apnea stably controlled via CPAPwould not be an exclusion).
7. Subject has active medical device implant anywhere in the body (including but notlimited to pacemakers, spinal cord stimulators, deep brain stimulators) or metalimplant at the site of study device electrode application.
8. Subject has severe peripheral neuropathy affecting the lower legs and/or subject hasneuropathy and is unable to clearly distinguish between symptoms of neuropathy andsymptoms of RLS.
9. Subject has been diagnosed with one of the following conditions:

• Epilepsy or other seizure disorder
• Current, active or acute or chronic infection other than common cold
• A malignancy within the past 5 years (not including basal or squamous cell skincancer)
• Stage 4-5 chronic kidney disease or renal failure
• Severe movement disorder symptoms (Parkinson's disease, Huntington's disease,dyskinesia, dystonia)
• Deep vein thrombosis
• Multiple sclerosis

10. Subject has moderate or severe cognitive disorder or mental illness.
11. Subject has current diagnosis of iron-deficient anemia or history of iron-deficientanemia within the past year.
12. Subject has known allergy to device materials or severe previous reaction to medicaladhesives or bandages.
13. Subject has severe edema affecting lower legs.
14. Subject has any of the following at or near the location of device application.

• Acute injury
• Cellulitis
• Open sores
• Other skin condition

15. Subject is on dialysis or anticipated to start dialysis while participating in thestudy
16. During the NTX100 calibration process, which is identical for subjects in the activeand sham arms, subject reports not feeling stimulation sensations up to an intensityof 30mA, the subject finds stimulation intensities less than 15 mA to be uncomfortableor distracting, or the device does not properly fit the subject.
17. Subject has received an investigational drug or device within the last 30 days or isplanning to receive an investigational device during the duration of the study.
18. Subject is pregnant or trying to become pregnant.
19. Subject has undergone a major surgery (excluding dental work) in the previous 30 days.
20. Subject is unable or unwilling to comply with study requirements.
21. Subject has another medical condition that may put the subject at risk as determinedby the investigator.
22. Subject has another medical condition that may affect validity of the study asdetermined by the investigator.