Restless Legs SyndromeNCT04874155

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

A study testing NTX100 Neuromodulation System - Active and NTX100 Neuromodulation System - Open-Label in people with Restless Legs Syndrome, run by Noctrix Health, Inc. at 7 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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 Read more about this study

Who is it for?: Ages 22 to 79 years
Conditions the study is for: Restless Legs Syndrome
What is being tested?: NTX100 Neuromodulation System - Active and NTX100 Neuromodulation System - Open-Label
Type of treatment: Medical device
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 133 participants
Where: 7 sitesUnited States
Study dates: 6 May 2021to 8 Apr 2022
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 22 to 79 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Show all 12Show fewer

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

Who cannot join

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)).

Show all 35Show fewer

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
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.
Subject has current diagnosis of iron-deficient anemia or history of iron-deficient anemia within the past year.
Subject has known allergy to device materials, electrode gel, polyurethane foam, or lycra (or severe previous reaction to medical adhesives or bandages).
Subject has severe edema affecting lower legs.
Subject has any of the following at or near the location of device application.
Acute injury
Cellulitis
Open sores
Other skin condition
Subject is on dialysis or anticipated to start dialysis while participating in the study.
During the NTX100 calibration process, which is identical for subjects in the active and sham arms, subject reports not feeling stimulation sensations up to an intensity of 30mA or finds stimulation intensities less than 15 milliamperes (mA) to be uncomfortable or distracting.
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 has undergone a major surgery (excluding dental work) in the 30 days prior to study entry.
Subject is unable or unwilling to comply with study requirements.
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.
Subject has a medical condition not listed above that may put the subject at risk as determined by the investigator

Trial locations and contacts

7 sites in 1 country.

City, postcode or hospital

7 sites in 1 country

United States7 sites

Neurotrials Research
Atlanta, Georgia, 30328
FutureSearch Trials of Neurology
Austin, Texas, 78731
Delta Waves, Inc.
Colorado Springs, Colorado, 95125
Bogan Sleep Consultants, LLC
Columbia, South Carolina, 29201
Ohio Sleep Medicine Institute
Dublin, Ohio, 43017
California Center for Sleep Disorders
San Leandro, California, 94578
Clayton Sleep Institute
St Louis, Missouri, 63123

Other trials in United States

About this study

Official title: A Multi-Center, Randomized, Double-Blind, Sham-Controlled Study to Evaluate the NTX100 Neuromodulation System for Patients With Medication-Refractory Primary Restless Legs Syndrome (RLS) - The RESTFUL Study

Read the detailed description

The study consists of a series of two 4-week phases:

Phase 1: Prospective, double-blinded, 1:1 randomized (Active treatment: Sham control)

Phase 2: Prospective, non-randomized, non-blinded, Active treatment

Conditions: Restless Legs Syndrome
Being tested: NTX100 Neuromodulation System - Active, NTX100 Neuromodulation System - Sham, NTX100 Neuromodulation System - Open-Label
Medical subject headings: Restless Legs Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

NTX100 Neuromodulation System - ActiveDevice
Noninvasive peripheral nerve stimulation device programmed to active mode.
NTX100 Neuromodulation System - ShamDevice
Noninvasive peripheral nerve stimulation device programmed to sham mode.
NTX100 Neuromodulation System - Open-LabelDevice
Noninvasive peripheral nerve stimulation device programmed to active mode.

Study groups in NCT04874155
Study group	Role	What they receive
Active neurostimulation	Active comparator	Noninvasive peripheral nerve stimulation device programmed to deliver active stimulation - Phase 1 Receives: Device: NTX100 Neuromodulation System - Active
Sham neurostimulation	Sham comparator	Noninvasive peripheral nerve stimulation device programmed to deliver non-therapeutic (sham) stimulation - Phase 1 Receives: 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 Receives: Device: NTX100 Neuromodulation System - Open-Label

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Week 4

Secondary outcomes (6)

Responder Rate on Patient Global Impressions-Improvement (PGI-I) Scale
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.
Measured: Week 4
Mean Change From Baseline in International Restless Legs Syndrome Study Group Rating Scale (IRLS) Score
IRLS is a participant-rated questionnaire that rates RLS severity from 0-40, where 40 is the most severe.
Measured: Week 4
Mean Change From Baseline in Medical Outcomes Study Sleep Problems Index II (MOS-II) Score
MOS-II is a subscale of the participant-rated MOS questionnaire that measures subjective sleep quality. The MOS-I (6-items) and MOS-II (9-items) are the two validated subscales of the 12-item MOS Sleep Scale. Both are scored from 0 to 100, where 100 corresponds to the worst possible sleep problems and 0 corresponds to no sleep problems. See https://labs.dgsom.ucla.edu/hays/files/view/docs/surveys/sleep/sleepman-112603.pdf for more information.
Measured: Week 4
Mean Change From Baseline in Medical Outcomes Study Sleep Problems Index I (MOS-I) Score
MOS-I is a subscale of the participant-rated MOS questionnaire that measures subjective sleep quality. The MOS-I (6-items) and MOS-II (9-items) are the two validated subscales of the 12-item MOS Sleep Scale. Both are scored from 0 to 100, where 100 corresponds to the worst possible sleep problems and 0 corresponds to no sleep problems. See https://labs.dgsom.ucla.edu/hays/files/view/docs/surveys/sleep/sleepman-112603.pdf for more information.
Measured: Week 4
Mean Clinical Global Impressions-Improvement (CGI-I) Scale Rating
Mean rating on the investigator-rated 7-point Likert CGI-I scale, where lower scores indicate improvement. Possible choices (followed by scale value) are: Very much improved (1), Much improved (2), Minimally improved (3), No change (4), Minimally worse (5), Much worse (6), Very Much Worse (7).
Measured: Week 4
Score for Question #7 of the International Restless Legs Syndrome Study Group Rating Scale (IRLS)
Question #7 of the IRLS assesses the participant-rated frequency (days/week) of RLS symptoms on a scale from 0 to 4, where lower scores indicate less frequent symptoms
Measured: Week 8

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

6 May 20218 Apr 2022

First posted5 May 2021
Study start6 May 2021
Primary completion18 Mar 2022
Study completion8 Apr 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Restless Legs SyndromeStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Model description: Study consists of two phases. Phase 1: Randomized 1:1 between Active treatment and Sham control Phase 2: Non-randomized, Active treatment
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 133 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04874155
Sponsor's protocol ID: CT-04
Status last verified: Aug 2024
First submitted: 3 May 2021
Last updated: 8 Oct 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: Yes

Publications

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.
PubMed 37458698

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruiting
Neuromodulation to Overcome Severe Restless Legs Syndrome
Restless Leg Syndrome (RLS), Spinal Cord Stimulation (SCS)
Not yet recruitingPhase 2
Tolerability and Efficacy of CBD Extract for RLS Treatment
Restless Leg Syndrome
Recruiting
Functional Connectivity of the Interoceptive Network in RLS
Restless Legs Syndrome
Not yet recruitingPhase 2
Intravenous Iron in the Management of Drug-resistant Restless Legs syndromeI
Restless Legs Syndrome (RLS)
Not yet recruiting
The Effect of Acupressure on Restless Legs Syndrome and Pruritus in Patients Undergoing Hemodialysis
Restless Leg Syndrome (RLS)

All Restless Legs Syndrome trials

Study at a glance

From the registry record, last updated by the sponsor on 8 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multi-Center, Randomized, Double-Blind, Sham-Controlled Study to Evaluate the NTX100 Neuromodulation System for Patients With Medication-Refractory Primary Restless Legs Syndrome (RLS) - The RESTFUL Study
ClinicalTrials.gov ID: NCT04874155
Acronym / sponsor ID: CT-04
Conditions: Restless Legs Syndrome
Study type: Interventional
Recruitment status: Completed
Enrolment: 133 participants (actual)
Lead sponsor: Noctrix Health, Inc.Industry (pharma, biotech, devices)
Study start: 6 May 2021 (actual)
Primary completion: 18 Mar 2022 (actual)
Study completion: 8 Apr 2022 (actual)
First posted: 5 May 2021 (actual)
Results: Posted 19 Sep 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

The study consists of a series of two 4-week phases:

Phase 1: Prospective, double-blinded, 1:1 randomized (Active treatment: Sham control)

Phase 2: Prospective, non-randomized, non-blinded, Active treatment

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 3
Model description: Study consists of two phases. Phase 1: Randomized 1:1 between Active treatment and Sham control Phase 2: Non-randomized, Active treatment

Arm	Type	Receives
Active neurostimulation	Active comparator	Device: NTX100 Neuromodulation System - ActiveNoninvasive peripheral nerve stimulation device programmed to deliver active stimulation - Phase 1
Sham neurostimulation	Sham comparator	Device: NTX100 Neuromodulation System - ShamNoninvasive peripheral nerve stimulation device programmed to deliver non-therapeutic (sham) stimulation - Phase 1
Open-Label	Active comparator	Device: NTX100 Neuromodulation System - Open-LabelOpen-Label - Phase 2 lasting 4-wks, during which all subjects will receive open-label Active treatment

Who may qualify

Ages: 22 to 79 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (12 listed)

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.

Key exclusion criteria (35 listed)

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).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
NTX100 Neuromodulation System - ActiveNoninvasive peripheral nerve stimulation device programmed to active mode.	Device	Active neurostimulation
NTX100 Neuromodulation System - ShamNoninvasive peripheral nerve stimulation device programmed to sham mode.	Device	Sham neurostimulation
NTX100 Neuromodulation System - Open-LabelNoninvasive peripheral nerve stimulation device programmed to active mode.	Device	Open-Label

Primary outcome

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
Time frame: Week 4
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.

6 secondary outcomes

Responder Rate on Patient Global Impressions-Improvement (PGI-I) Scale
Time frame: Week 4
Mean Change From Baseline in International Restless Legs Syndrome Study Group Rating Scale (IRLS) Score
Time frame: Week 4
Mean Change From Baseline in Medical Outcomes Study Sleep Problems Index II (MOS-II) Score
Time frame: Week 4
Mean Change From Baseline in Medical Outcomes Study Sleep Problems Index I (MOS-I) Score
Time frame: Week 4
Mean Clinical Global Impressions-Improvement (CGI-I) Scale Rating
Time frame: Week 4
Score for Question #7 of the International Restless Legs Syndrome Study Group Rating Scale (IRLS)
Time frame: Week 8

Results and safety

Results posted to the registry on 19 Sep 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
TOMAC Group	68	65
Sham Control Group	65	62

Primary outcome: 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

Time frame: Week 4. Count of participants. Unit: Participants

Measure	TOMAC Group n = 68	Sham Control Group n = 65
Value	29	10

Population analysed: Primary Efficacy Endpoint (CGI-I Responder Rate at Week 4) - (ITT Population)

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: 8 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
TOMAC Group	0 of 68 (0%)	28 of 68 (41.2%)	0 of 68
Sham Control Group	0 of 65 (0%)	23 of 65 (35.4%)	0 of 65

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 37458698Bogan 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.

Related trials for Restless Legs Syndrome

Not yet recruiting
Neuromodulation to Overcome Severe Restless Legs Syndrome
Restless Leg Syndrome (RLS), Spinal Cord Stimulation (SCS)
Not yet recruitingPhase 2
Tolerability and Efficacy of CBD Extract for RLS Treatment
Restless Leg Syndrome
Recruiting
Functional Connectivity of the Interoceptive Network in RLS
Restless Legs Syndrome
Not yet recruitingPhase 2
Intravenous Iron in the Management of Drug-resistant Restless Legs syndromeI
Restless Legs Syndrome (RLS)
Not yet recruiting
The Effect of Acupressure on Restless Legs Syndrome and Pruritus in Patients Undergoing Hemodialysis
Restless Leg Syndrome (RLS)

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Jonathan D Charlesworth, PhD study director

Noctrix Health, Inc.

7 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing NTX100 Neuromodulation System - Active and NTX100 Neuromodulation System - Open-Label in people with Restless Legs Syndrome, run by Noctrix Health, Inc. at 7 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: Week 4). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04874155, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2024; AzTrials last refreshed its copy on 27 Oct 2026.