Noninvasive Peripheral Nerve Stimulation for Restless Legs Syndrome During Opioid Medication Reduction
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Noninvasive Peripheral Nerve Stimulation (NPNS) NPNS device programmed to deliver active stimulation. |
Device: Noninvasive Peripheral Nerve Stimulation (NPNS)
NPNS device programmed to deliver active stimulation.
|
Outcome Measures
Primary Outcome Measures
- Opioid reduction tolerability rate during step-down #1 as measured by Clinical Global Impression - Improvement (CGI-I) scale [1 week assessment period for step-down #1 compared to 1 week baseline period]
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.
Secondary Outcome Measures
- Opioid reduction tolerability rate during step-down #2 as measured by Clinical Global Impression - Improvement (CGI-I) scale [1 week assessment period for step-down #2 compared to 1 week baseline period]
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
- Change from baseline in International Restless Legs Syndrome Study Group Rating Scale (IRLS) score during step-down #1 [1 week assessment period for step-down #1 compared to 1 week baseline period]
IRLS is a participant-rated questionnaire that rates RLS severity from 0-40, where 40 is the most severe.
- Change from baseline in IRLS score during step-down #2 [1 week assessment period for step-down #2 compared to 1 week baseline period]
IRLS is a participant-rated questionnaire that rates RLS severity from 0-40, where 40 is the most severe.
- Maximal tolerated reduction in opioid dose [Time Frame: 1 week assessment period for final step-down compared to 1 week baseline period]
Maximal percentage reduction in opioid dose relative to baseline associated with a CGI-I score of 5 or less, averaged across subjects.
Other Outcome Measures
- NPNS tolerability rate [Full duration of NPNS usage through study completion, up to 9 weeks]
Percentage of subjects who withdraw from study prior to the Extension Phase citing lack of tolerability of NPNS as the primary reason for withdrawal.
- Frequency of Grade 2 or higher NPNS-related adverse events. [Full duration of NPNS usage through study completion, up to 9 weeks]
Frequency of Grade 2 or higher NPNS-related adverse events.
- Frequency of Grade 3 or higher NPNS-related adverse events. [Full duration of NPNS usage through study completion, up to 9 weeks]
Frequency of Grade 3 or higher NPNS-related adverse events.
- NPNS compliance during step-down #1 [1 week assessment period for step-down #1]
Frequency of device usage during assessment period during step-down #1
- NPNS compliance during step-down #2 [1 week assessment period for step-down #2]
Frequency of device usage during assessment period during step-down #2
Eligibility Criteria
Criteria
Inclusion Criteria:
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Subject has received a medical diagnosis of primary restless legs syndrome (RLS)
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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.
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RLS symptoms are most significant in the subject's legs and/or feet.
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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.
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Subject is 18 to 89 years of age (inclusive) when written informed consent is obtained.
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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.
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Subject has been taking a stable dose and schedule of prescription opioids for RLS for at least 3 months prior to enrollment.
Exclusion Criteria:
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Subject has RLS that is known to be caused by another diagnosed condition (i.e. secondary RLS).
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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).
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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).
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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
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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
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Subject has any of the following at the location of device application: Acute injury, Cellulitis, Open sores
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Subject has a malignancy within the past 5 years (not including basal or squamous cell skin cancer)
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Subject is on dialysis or anticipated to start dialysis while participating in the study
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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.
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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.
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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).
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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.
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Subject has another medical condition that may affect validity of the study as determined by the investigator.
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Subject is unable or unwilling to comply with study requirements.
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Moderate or severe cognitive disorder or mental illness.
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Subject has prior experience with Noctrix Health NPNS devices.
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Subject has active implantable medical devices anywhere in the body (including pacemakers), or metal implant at the site of study device electrode application.
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Subject has known allergy to electrode gel, polyurethane foam, or lycra.
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Subject is pregnant or trying to become pregnant.
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Subject has undergone a major surgery (excluding dental work) in the previous 30 days.
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Subject has another medical condition that may put the subject at risk as determined by the investigator.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mark J Buchfuhrer private practice | Downey | California | United States | 90241 |
| 2 | Ohio Sleep Medicine Institute | Dublin | Ohio | United States | 43017 |
Sponsors and Collaborators
- Noctrix Health, Inc.
- National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
- Study Director: Jonathan D Charlesworth, PhD, Noctrix Health, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CT-03
- R44NS117294