Noninvasive Peripheral Nerve Stimulation for Medication-Refractory Primary RLS (The RESTFUL Study)

NCT04874155 | Completed Results FDA Device

• 1 other identifier: CT-04
• Study Type: interventional
• Target: 133
• Locations: 1 country
• Sites: 7

Brief Summary

Multi-center, prospective double-blind randomized controlled pivotal study of noninvasive peripheral nerve stimulation (NPNS) with the NTX100 Neuromodulation System for patients with medication-refractory moderate-severe primary RLS

Conditions

Restless Legs Syndrome

Outcome Measures

Primary Outcomes (1)

• Number of Subjects for Which the Clinician Reported "Much Improved" or "Very Much Improved" on the Clinical Global Impressions-Improvement (CGI-I) Scale for TOMAC Compared to Sham

  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 4

Secondary Outcomes (6)

• Responder Rate on Patient Global Impressions-Improvement (PGI-I) Scale

  Week 4

• Mean Change From Baseline in International Restless Legs Syndrome Study Group Rating Scale (IRLS) Score

  Week 4

• Mean Change From Baseline in Medical Outcomes Study Sleep Problems Index II (MOS-II) Score

  Week 4

• Mean Change From Baseline in Medical Outcomes Study Sleep Problems Index I (MOS-I) Score

  Week 4

• Mean Clinical Global Impressions-Improvement (CGI-I) Scale Rating

  Week 4

Study Arms (3)

Active neurostimulation

ACTIVE COMPARATOR

Noninvasive peripheral nerve stimulation device programmed to deliver active stimulation - Phase 1

Device: NTX100 Neuromodulation System - Active

Sham neurostimulation

SHAM COMPARATOR

Noninvasive peripheral nerve stimulation device programmed to deliver non-therapeutic (sham) stimulation - Phase 1

Device: NTX100 Neuromodulation System - Sham

Open-Label

ACTIVE COMPARATOR

Open-Label - Phase 2 lasting 4-wks, during which all subjects will receive open-label Active treatment

Device: NTX100 Neuromodulation System - Open-Label

Interventions

NTX100 Neuromodulation System - Active DEVICE

Noninvasive peripheral nerve stimulation device programmed to active mode.

Active neurostimulation

NTX100 Neuromodulation System - Sham DEVICE

Noninvasive peripheral nerve stimulation device programmed to sham mode.

Sham neurostimulation

NTX100 Neuromodulation System - Open-Label DEVICE

Noninvasive peripheral nerve stimulation device programmed to active mode.

Open-Label

Eligibility Criteria

• Age: 22 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject has received a medical diagnosis of primary restless legs syndrome (RLS).
• Subject is refractory to RLS medication (as defined in section 7.3).
• Subject has moderate-severe RLS symptoms as defined by a score of 15 or greater points on IRLS (International Restless Legs Syndrome Study Group Rating Scale \[12\]) over the week prior to study entry.
• Subject has RLS symptoms 2 or more nights per week during the week prior to study entry as defined by a score of 2, 3, or 4 on IRLS question #7.
• RLS symptoms are most significant in the subject's lower legs and/or feet.
• RLS symptoms are most significant at bedtime, after bedtime, and/or in the 2 hours before bedtime.
• RLS symptoms between 10am and 6pm are not severe.
• 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.
• Subject agrees to not make major lifestyle changes during the study including diet, exercise, career, or other changes that would affect bedtime.
• 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 ≥ 22 and ≤ 79 years of age 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

You may not qualify if:

• Subject has RLS that is known to be caused by another diagnosed condition (i.e. secondary RLS).
• Subject is taking an unstable or inconsistent dose or schedule of medication that is likely to impact RLS symptoms, such as antidepressants, sleep medications, or sedative antihistamines or has changed dosage within the past 30 days.
• Subject has changed dose and schedule of RLS medications within the month prior to study entry or is otherwise on an inconsistent dose or schedule of RLS medications.
• Subject reports having significant prior experience with neurostimulation devices (including but not limited to transcutaneous electrical nerve stimulation (TENS) devices) or subject has prior experience with neurostimulation devices developed by the study sponsor.
• Subject was misdiagnosed with RLS, as determined by the investigator (e.g. actual diagnosis of Periodic Limb Movement Disorder (PLMD), arthritis, leg spasms or neuropathy without comorbid RLS).
• Subject has a sleep disorder other than RLS that interferes with sleep at the present time (except for obstructive sleep apnea that is stably controlled via Continuous Positive Airway Pressure (CPAP)).
• 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 in the leg.
• Subject has failed a nerve conduction study prescribed by a physician or has been diagnosed with severe peripheral neuropathy.
• Subject reports that bedtime is typically outside of 9pm-3am or reports that bedtime regularly varies by more than 4 hours, such as due to shift work.
• On nights with no RLS symptoms (if any), subject reports typical sleep onset latency of \>60min.
• 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 skin cancer)
• Stage 4-5 chronic kidney disease or renal failure

Sponsors & Collaborators

• Noctrix Health, Inc.: lead

Study Sites (7)

California Center for Sleep Disorders

San Leandro, California, 94578, United States

Location

Delta Waves, Inc.

Colorado Springs, Colorado, 95125, United States

Location

Neurotrials Research

Atlanta, Georgia, 30328, United States

Location

Clayton Sleep Institute

St Louis, Missouri, 63123, United States

Location

Ohio Sleep Medicine Institute

Dublin, Ohio, 43017, United States

Location

Bogan Sleep Consultants, LLC

Columbia, South Carolina, 29201, United States

Location

FutureSearch Trials of Neurology

Austin, Texas, 78731, United States

Location

Related Publications (1)

• Bogan RK, Roy A, Kram J, Ojile J, Rosenberg R, Hudson JD, Scheuller HS, Winkelman JW, Charlesworth JD. Efficacy and safety of tonic motor activation (TOMAC) for medication-refractory restless legs syndrome: a randomized clinical trial. Sleep. 2023 Oct 11;46(10):zsad190. doi: 10.1093/sleep/zsad190.

  PMID: 37458698 DERIVED

MeSH Terms

Conditions

Restless Legs Syndrome

Condition Hierarchy (Ancestors)

Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Parasomnias; Mental Disorders

Results Point of Contact

• Title: Jonathan Charlesworth, PhD
• Organization: Noctrix Health, Inc.

jcharlesworth@noctrixhealth.com

804-683-4279

Study Officials

• Jonathan D Charlesworth, PhD

  Noctrix Health, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Study consists of two phases. Phase 1: Randomized 1:1 between Active treatment and Sham control Phase 2: Non-randomized, Active treatment

Study Record Dates

• First Submitted: May 3, 2021
• First Posted: May 5, 2021
• Study Start: May 6, 2021
• Primary Completion: March 18, 2022
• Study Completion: April 8, 2022
• Last Updated: October 8, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-08

Locations

US (7)