Extension Study Evaluating NTX100 Neuromodulation System for Medication-Refractory Primary RLS

Study Overview
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Brief Summary
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Multi-center, prospective open-label extension study of noninvasive peripheral nerve stimulation (NPNS) with the NTX100 Neuromodulation System for patients with medication-refractory moderate- severe primary RLS

Detailed Description
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This is an extension study only inviting subjects who have previously completed the RESTFUL Study (NCT04874155). Each study subject is enrolled into one of the following Arms: Arm 1 (Direct Roll-Over Extension): 24-week open-label NPNS followed by 8-weeks of no treatment, no delay after completion of the RESTFUL Study Arm 2 (Control Group): 24-weeks of no treatment

Official Title
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Open-label Extension Study to Evaluate Longer-Duration Response to the NTX100 Neuromodulation System for Patients With Medication-Refractory Primary Restless Legs Syndrome (RLS)

Conditions
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Restless Legs Syndrome

Intervention / Treatment
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* Device: NTX100 Neuromodulation System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject previously completed the RESTFUL Study (NCT04874155). Subject has signed a valid, IRB-approved informed consent form, can understand the requirements of the study and instructions for device usage, and can converse in English. [applicable to Arm 1 only] Subject agrees to not change dosage or schedule of any medications that are known to impact RLS symptoms during the study, including RLS medications, antidepressants, sleep medications, or sedative antihistamines. Exclusion Criteria: [applicable to Arm 1 only] Subject has active medical device implant anywhere in the body (including but not limited to pacemakers, spinal cord stimulators, deep brain stimulators) or metal implant at the site of study device electrode application. [applicable to Arm 1 only] 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 [and except for acute infections with mild symptoms] A malignancy within the past 5 years (not including basal or squamous cell skin cancer) 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 Subject has moderate or severe cognitive disorder or mental illness. [applicable to Arm 1 only] Subject has known allergy to device materials, electrode gel, polyurethane foam, or lycra (or severe previous reaction to medical adhesives or bandages). [applicable to Arm 1 only] Subject has severe edema affecting lower legs. [applicable to Arm 1 only] Subject has any of the following at or near the location of device application. Acute injury Cellulitis Open sores Other skin condition [applicable to Arm 1 only] Subject is on dialysis or anticipated to start dialysis while participating in the study. [applicable to Arm 1 only] Subject has received another investigational device or drug within 30 days before study entry, is planning to receive another investigational device or drug during the study, or is planning to change RLS medications during the study. Subject is unable or unwilling to comply with study requirements. [applicable to Arm 1 only] Subject is pregnant or trying to become pregnant. Subject has a medical condition not listed above that may affect validity of the study as determined by the investigator. [applicable to Arm 1 only] Subject has a medical condition not listed above that may put the subject at risk as determined by the investigator. Subject was unwilling or unable to follow instructions in the RESTFUL Study, including missing 2 or more follow-up evaluations. [applicable to Arm 1 only] Subject failed to properly operate the investigational devices during Weeks 5-8 of the RESTFUL Study. [applicable to Arm 1 only] Subject experienced a significantly higher than expected rate of device malfunctions in the RESTFUL Study, such that the malfunctions appeared to be directly related to the subject's pattern of use.

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 80 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1 - Direct Roll-Over Extension<br>24-wks of Active neurostimulation - Noninvasive peripheral nerve stimulation device programmed to deliver active stimulation; followed by 8-wks of No Intervention | Device: NTX100 Neuromodulation System<br>* Active Noninvasive peripheral nerve stimulation device programmed to active mode<br>|
| No Intervention: Arm 2 - Control Group<br>24-wks of No Intervention | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responder rate on Clinical Global Impressions-Improvement (CGI-I) scale in Arm 1 | Responder rate is defined as the proportion of responses of Much Improved or Very Much Improved relative to baseline on the investigator-rated 7-point CGI-I scale. | Week 24 of Arm 1 relative to entry to the RESTFUL study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responder rate on Patient Global Impressions-Improvement (PGI-I) scale in Arm 1 | Responder rate is defined as the proportion of responses of Much Improved or Very Much Improved relative to baseline on the participant-rated 7-point PGI-I scale. | Week 24 of Arm 1 relative to entry to the RESTFUL study | 
| Mean International Restless Legs Syndrome Study Group Rating Scale (IRLS) score in Arm 1 | IRLS is a participant-rated questionnaire that rates RLS severity from 0-40, where 40 is the most severe. | Week 24 of Arm 1 relative to entry to the RESTFUL study | 
| Mean Medical Outcomes Study Sleep Problems Index II (MOS-II) score in Arm 1 | MOS-II is a subscale of the participant-rated MOS questionnaire that measures subjective sleep quality. | Week 24 of Arm 1 relative to entry to the RESTFUL study | 
| Mean Medical Outcomes Study Sleep Problems Index I (MOS-I) score in Arm 1 | MOS-I is a subscale of the participant-rated MOS questionnaire that measures subjective sleep quality. | Week 24 of Arm 1 relative to entry to the RESTFUL study | 
| Frequency of RLS symptoms based on Question #7 in the International Restless Legs Syndrome Study Group Rating Scale (IRLS) score in Arm 1 | IRLS Question #7 is a participant-rated question that measures frequency of RLS symptoms in terms of days per week. | Week 24 of Arm 1 relative to entry to the RESTFUL study |