Clinical trial NCT04698343: Noninvasive Peripheral Nerve Stimulation for Restless Legs Syndrome During Opioid Medication Reduction
Official title: Exploratory Study Assessing the Response of Restless Legs Syndrome (RLS) Patients to Non-invasive Peripheral Nerve Stimulation (NPNS) During Opioid Medication Reduction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Restless Legs Syndrome
Lead sponsor: Noctrix Health, Inc.
Sponsor class: INDUSTRY
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2021-01-06
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Subjects Without a Clinically Significant Increase in RLS Symptoms During the First Phase Involving an Opioid Dose Reduction of >= 20% Relative to Baseline.
timeFrame: Week 1
Secondary outcomes:
measure: Percentage of Subjects Without a Clinically Significant Increase in RLS Symptoms During the First Phase Involving an Opioid Dose Reduction of >= 1/3 Relative to Baseline.
timeFrame: 1 week
measure: Change From Baseline in International Restless Legs Syndrome Study Group Rating Scale (IRLS) Score During Step-down #1 With an Opioid Dose Reduction of >=20%
timeFrame: 1 week
measure: Change From Baseline in International Restless Legs Syndrome Study Group Rating Scale (IRLS) Score During Step-down #2 With an Opioid Dose Reduction of >=1/3
timeFrame: 1 week into Step-down #2
measure: Maximum Percent Change in Opioid Dose Relative to Baseline Without a Clinically Significant Increase in RLS Symptoms.
timeFrame: 1 week into final step-down
Other outcomes:
measure: NPNS Tolerability Rate - Percentage of Subjects Who Withdrew From Optional Phase 3 Citing Lack of Tolerability of NPNS as the Primary Reason for Withdrawal.
timeFrame: Up to 9 weeks
measure: Percentage of Grade 2 or Higher NPNS-related Adverse Events.
timeFrame: Up to 9 weeks
measure: Percentage of Grade 3 or Higher NPNS-related Adverse Events.
timeFrame: Up to 9 weeks
measure: NPNS Adherence Ratio During Step-down #1 and Step-down #2.
timeFrame: 1 week post step-down
Locations:
city: Downey
country: United States
facility: Mark J Buchfuhrer private practice
state: California
city: Dublin
country: United States
facility: Ohio Sleep Medicine Institute
state: Ohio
Study officials:
affiliation: Noctrix Health, Inc.
name: Jonathan D Charlesworth, PhD
role: STUDY_DIRECTOR
References: