Restless Legs SyndromeNCT04698343
Noninvasive Peripheral Nerve Stimulation for Restless Legs Syndrome During Opioid Medication Reduction
A study testing Noninvasive Peripheral Nerve Stimulation (NPNS) in people with Restless Legs Syndrome, run by Noctrix Health, Inc. at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 89 years
- Conditions the study is for
- Restless Legs Syndrome
- What is being tested?
- Noninvasive Peripheral Nerve Stimulation (NPNS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 2 sitesUnited States
- Study dates
- 6 Apr 2021to 28 Mar 2023
- 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 18 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 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.
Who cannot join
- 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
Show all 21Show fewer
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Mark J Buchfuhrer private practice
Downey, California, 90241
Ohio Sleep Medicine Institute
Dublin, Ohio, 43017
About this study
Official title: Exploratory Study Assessing the Response of Restless Legs Syndrome (RLS) Patients to Non-invasive Peripheral Nerve Stimulation (NPNS) During Opioid Medication Reduction
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.
Read the 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.
- Conditions
- Restless Legs Syndrome
- Being tested
- Noninvasive Peripheral Nerve Stimulation (NPNS)
- 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.
Noninvasive Peripheral Nerve Stimulation (NPNS)Device
NPNS device programmed to deliver active stimulation.
| Study group | Role | What they receive |
|---|---|---|
| Noninvasive Peripheral Nerve Stimulation (NPNS) | Experimental | NPNS device programmed to deliver active stimulation. Receives: Device: Noninvasive Peripheral Nerve Stimulation (NPNS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
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. The clinically significant increase was assessed by determining the Clinician Global Impression of Improvement (CGI-I) score for the subject. 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). Scores of 6 or 7 would be considered a clinically significant increase in RLS Symptoms.
Measured: Week 1
Secondary outcomes (4)
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.
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. The clinically significant increase was assessed by determining the Clinician Global Impression of Improvement (CGI-I) score for the subject. 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). Scores of 6 or 7 would be considered a clinically significant increase in RLS Symptoms.
Measured: 1 week
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%
IRLS is a participant-rated questionnaire that rates RLS severity from 0-40, where 40 is the most severe.
Measured: 1 week
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
IRLS is a participant-rated questionnaire that rates RLS severity from 0-40, where 40 is the most severe.
Measured: 1 week into Step-down #2
Maximum Percent Change in Opioid Dose Relative to Baseline Without a Clinically Significant Increase in RLS Symptoms.
The clinically significant increase was assessed by determining the Clinician Global Impression of Improvement (CGI-I) score for the subject. 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). Scores of 6 or 7 would be considered a clinically significant increase in RLS Symptoms.
Measured: 1 week into final step-down
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2021
- Study start6 Apr 2021
- Primary completion27 Feb 2023
- Study completion28 Mar 2023
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 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
- NCT04698343
- Sponsor's protocol ID
- CT-03
- Other IDs
- R44NS117294
- Status last verified
- Sep 2024
- First submitted
- 4 Jan 2021
- Last updated
- 19 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Buchfuhrer MJ, Roy A, Rodriguez S, Charlesworth JD. Adjunctive tonic motor activation enables opioid reduction for refractory restless legs syndrome: a prospective, open-label, single-arm clinical trial. BMC Neurol. 2023 Nov 21;23(1):415. doi: 10.1186/s12883-023-03462-6.
PubMed 37990163
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exploratory Study Assessing the Response of Restless Legs Syndrome (RLS) Patients to Non-invasive Peripheral Nerve Stimulation (NPNS) During Opioid Medication Reduction
- ClinicalTrials.gov ID
- NCT04698343
- Acronym / sponsor ID
- CT-03
- Conditions
- Restless Legs Syndrome
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Noctrix Health, Inc.Industry (pharma, biotech, devices)
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- 6 Apr 2021 (actual)
- Primary completion
- 27 Feb 2023 (actual)
- Study completion
- 28 Mar 2023 (actual)
- First posted
- 6 Jan 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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Noninvasive Peripheral Nerve Stimulation (NPNS) | Experimental | Device: Noninvasive Peripheral Nerve Stimulation (NPNS)NPNS device programmed to deliver active stimulation. |
Who may qualify
- Ages
- 18 to 89 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (21 listed)
- 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
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 |
|---|---|---|
| Noninvasive Peripheral Nerve Stimulation (NPNS)NPNS device programmed to deliver active stimulation. | Device | Noninvasive Peripheral Nerve Stimulation (NPNS) |
Primary outcome
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.
Time frame: Week 1
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. The clinically significant increase was assessed by determining the Clinician Global Impression of Improvement (CGI-I) score for the subject. 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). Scores of 6 or 7 would be considered a clinically significant increase in RLS Symptoms.
4 secondary outcomes
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.
Time frame: 1 week
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%
Time frame: 1 week
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
Time frame: 1 week into Step-down #2
Maximum Percent Change in Opioid Dose Relative to Baseline Without a Clinically Significant Increase in RLS Symptoms.
Time frame: 1 week into final step-down
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37990163Buchfuhrer MJ, Roy A, Rodriguez S, Charlesworth JD. Adjunctive tonic motor activation enables opioid reduction for refractory restless legs syndrome: a prospective, open-label, single-arm clinical trial. BMC Neurol. 2023 Nov 21;23(1):415. doi: 10.1186/s12883-023-03462-6.
- Individual participant dataSharing planned: No
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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.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Noninvasive Peripheral Nerve Stimulation (NPNS) in people with Restless Legs Syndrome, run by Noctrix Health, Inc. at 2 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 7 inclusion and 21 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 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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. 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?
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. (time frame: Week 1). 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 NCT04698343, 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 19 Sep 2024.