Restless Legs SyndromeNCT05214963
Noninvasive Peripheral Nerve Stimulation for Medication-Naive and Medication-Refractory RLS
A study testing NTX100 Neuromodulation System - Active in people with Restless Legs Syndrome, run by Noctrix Health, Inc. at 3 sites in United States.
Trial summary
Prospective multi-site randomized sham-controlled study evaluating tolerability and efficacy of noninvasive peripheral nerve stimulation (NPNS) for patients with moderate-severe primary Restless Legs Syndrome (RLS) who are either medication-naive or medication-refractory. Read more about this study
- Who is it for?
- Ages 22 to 89 years
- Conditions the study is for
- Restless Legs Syndrome
- What is being tested?
- NTX100 Neuromodulation System - Active
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 58 participants
- Where
- 3 sitesUnited States
- Study dates
- 8 Mar 2022to 24 Oct 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 89 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 either medication-naïve or medication-refractory.
- 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) over the week prior to study entry.
- RLS symptoms interfered with sleep on at least 3 nights per week during the month prior to study entry.
- RLS symptoms are most significant in the subject's lower legs and/or feet.
- RLS symptoms are most significant after 6pm.
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- 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 that would significantly affect bedtime, such as major changes to diet, exercise, or career.
- 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 ≤ 89 years of age when written informed consent is obtained.
- 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.
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 has prior experience with Noctrix Health NPNS devices.
- Subject was misdiagnosed with RLS, as determined by the investigator (e.g. actual diagnosis of PLMD, arthritis, leg spasms or neuropathy without comorbid RLS).
- Subject has a primary sleep disorder other than RLS that significantly interferes with sleep at the present time (e.g. obstructive sleep apnea stably controlled via CPAP would not be an exclusion).
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- 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.
- 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.
- 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 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, 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 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 is pregnant or trying to become pregnant.
- Subject has undergone a major surgery (excluding dental work) in the previous 30 days.
- Subject is unable or unwilling to comply with study requirements.
- Subject has another medical condition that may put the subject at risk as determined by the investigator.
- Subject has another medical condition that may affect validity of the study as determined by the investigator.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
SRI International Human Sleep Research Lab
Menlo Park, California, 94025
Sleep Medicine Specialists of California
San Ramon, California, 94583
Clayton Sleep Institute
St Louis, Missouri, 63123
About this study
Official title: Exploratory Clinical Study to Assess Tolerability, Safety, and Response to Non-invasive Peripheral Nerve Stimulation (NPNS) in Medication-naïve and Medication-refractory Restless Legs Syndrome (RLS) Patients
Prospective multi-site randomized sham-controlled study evaluating tolerability and efficacy of noninvasive peripheral nerve stimulation (NPNS) for patients with moderate-severe primary Restless Legs Syndrome (RLS) who are either medication-naive or medication-refractory.
Read the detailed description
The study consists of a series of two 2-week phases:
Phase 1: Baseline evaluation of RLS and sleep Phase 2: Prospective, single-blinded, 1:1 randomized evaluation of response to NPNS treatment (Active treatment: Sham control)
Additionally, subjects will have the option to consent to a third phase, which includes overnight polysomnography (PSG) evaluation of sleep with Active treatment and with no treatment (baseline), in randomized order.
- Conditions
- Restless Legs Syndrome
- Being tested
- NTX100 Neuromodulation System - Active, NTX100 Neuromodulation System - Sham
- 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
| Study group | Role | What they receive |
|---|---|---|
| Active neurostimulation | Active comparator | Noninvasive peripheral nerve stimulation device programmed to deliver active stimulation Receives: Device: NTX100 Neuromodulation System - Active |
| Sham neurostimulation | Sham comparator | Noninvasive peripheral nerve stimulation device programmed to deliver non-therapeutic (sham) stimulation Receives: Device: NTX100 Neuromodulation System - Sham |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tolerability based on Withdrawal Rate
Percentage of subjects who withdraw from study citing lack of tolerability of the study device as the primary reason for withdrawal
Measured: 2 weeks
Actigraphy-Based Sleep Efficiency
The ratio of wake after sleep onset to total sleep time, as measured by actigraphy
Measured: 1 week
Actigraphy-Based Total Sleep Time
Total sleep duration, as measured by actigraphy
Measured: 1 week
Secondary outcomes (9)
Frequency of Device Usage
The frequency of study device usage on nights with RLS symptoms
Measured: 2 weeks
Grade 2 or higher device-related adverse events
Frequency of Grade 2 or higher device-related adverse events
Measured: 2 weeks
Grade 3 or higher device-related adverse events
Frequency of Grade 3 or higher device-related adverse events
Measured: 2 weeks
Polysomnography-Based Sleep Efficiency
The ratio of wake after sleep onset to total sleep time, as measured by polysomnography
Measured: 1 night
Polysomnography-Based Total Sleep Time
Total duration of sleep, as measured by polysomnography
Measured: 1 night
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: 1 week
Patient Global Impressions of Improvement Responder Rate
Percentage of subjects with a Patient Global Impressions of Improvement (PGI-I) rating of Much Improved or Very Much Improved
Measured: 1 week
Polysomnography-Based Percentage of Stage 3 Sleep
Mean percentage of total sleep time in Stage 3 sleep, as measured by polysomnography
Measured: 1 night
Polysomnography-Based Percentage of REM Sleep
Mean percentage of total sleep time in REM sleep, as measured by polysomnography
Measured: 1 night
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2022
- Study start8 Mar 2022
- Primary completion24 Jul 2023
- Study completion24 Oct 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Parallel groups
- Model description
- Randomized 1:1 between Active treatment and Sham control
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- Noctrix Health, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jonathan D Charlesworth, PhD, Study director, Noctrix Health, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05214963
- Sponsor's protocol ID
- CT-02
- Other IDs
- R44NS117294
- Status last verified
- Dec 2023
- First submitted
- 18 Jan 2022
- Last updated
- 15 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Publications
Rigot SK, St Louis EK, Baker FC, Alawieh H, Singh H, Ojile J, Tekchandani J, Kolotovska V, Adlou B, Charlesworth JD. Acute effects of tonic motor activation (TOMAC) on sleep in adults with medication-refractory restless legs syndrome. Sleep Adv. 2026 Jun 11;7(3):zpag060. doi: 10.1093/sleepadvances/zpag060. eCollection 2026.
PubMed 42488517
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exploratory Clinical Study to Assess Tolerability, Safety, and Response to Non-invasive Peripheral Nerve Stimulation (NPNS) in Medication-naïve and Medication-refractory Restless Legs Syndrome (RLS) Patients
- ClinicalTrials.gov ID
- NCT05214963
- Acronym / sponsor ID
- CT-02
- Conditions
- Restless Legs Syndrome
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- Noctrix Health, Inc.Industry (pharma, biotech, devices)
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- 8 Mar 2022 (actual)
- Primary completion
- 24 Jul 2023 (actual)
- Study completion
- 24 Oct 2023 (actual)
- First posted
- 31 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Prospective multi-site randomized sham-controlled study evaluating tolerability and efficacy of noninvasive peripheral nerve stimulation (NPNS) for patients with moderate-severe primary Restless Legs Syndrome (RLS) who are either medication-naive or medication-refractory.
Detailed description
The study consists of a series of two 2-week phases:
Phase 1: Baseline evaluation of RLS and sleep Phase 2: Prospective, single-blinded, 1:1 randomized evaluation of response to NPNS treatment (Active treatment: Sham control)
Additionally, subjects will have the option to consent to a third phase, which includes overnight polysomnography (PSG) evaluation of sleep with Active treatment and with no treatment (baseline), in randomized order.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- Randomized 1:1 between Active treatment and Sham control
| Arm | Type | Receives |
|---|---|---|
| Active neurostimulation | Active comparator | Device: NTX100 Neuromodulation System - ActiveNoninvasive peripheral nerve stimulation device programmed to deliver active stimulation |
| Sham neurostimulation | Sham comparator | Device: NTX100 Neuromodulation System - ShamNoninvasive peripheral nerve stimulation device programmed to deliver non-therapeutic (sham) stimulation |
Who may qualify
- Ages
- 22 to 89 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Subject has received a medical diagnosis of primary restless legs syndrome (RLS).
- Subject is either medication-naïve or medication-refractory.
- 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) over the week prior to study entry.
- RLS symptoms interfered with sleep on at least 3 nights per week during the month prior to study entry.
- RLS symptoms are most significant in the subject's lower legs and/or feet.
Key exclusion criteria (33 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 has prior experience with Noctrix Health NPNS devices.
- Subject was misdiagnosed with RLS, as determined by the investigator (e.g. actual diagnosis of 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 |
Primary outcome
Tolerability based on Withdrawal Rate
Time frame: 2 weeks
Percentage of subjects who withdraw from study citing lack of tolerability of the study device as the primary reason for withdrawal
Actigraphy-Based Sleep Efficiency
Time frame: 1 week
The ratio of wake after sleep onset to total sleep time, as measured by actigraphy
Actigraphy-Based Total Sleep Time
Time frame: 1 week
Total sleep duration, as measured by actigraphy
9 secondary outcomes
Frequency of Device Usage
Time frame: 2 weeks
Grade 2 or higher device-related adverse events
Time frame: 2 weeks
Grade 3 or higher device-related adverse events
Time frame: 2 weeks
Polysomnography-Based Sleep Efficiency
Time frame: 1 night
Polysomnography-Based Total Sleep Time
Time frame: 1 night
International Restless Legs Syndrome Study Group Rating Scale (IRLS) score
Time frame: 1 week
Patient Global Impressions of Improvement Responder Rate
Time frame: 1 week
Polysomnography-Based Percentage of Stage 3 Sleep
Time frame: 1 night
Polysomnography-Based Percentage of REM Sleep
Time frame: 1 night
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2023.
- Derived from this study: PubMed 42488517Rigot SK, St Louis EK, Baker FC, Alawieh H, Singh H, Ojile J, Tekchandani J, Kolotovska V, Adlou B, Charlesworth JD. Acute effects of tonic motor activation (TOMAC) on sleep in adults with medication-refractory restless legs syndrome. Sleep Adv. 2026 Jun 11;7(3):zpag060. doi: 10.1093/sleepadvances/zpag060. eCollection 2026.
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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.
3 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 in people with Restless Legs Syndrome, run by Noctrix Health, Inc. at 3 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 11 inclusion and 33 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 15 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Tolerability based on Withdrawal Rate (time frame: 2 weeks). The study lists 3 primary outcomes in all. 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 NCT05214963, 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 15 Dec 2023.