Noninvasive Peripheral Nerve Stimulation for Restless Legs Syndrome

No longer recruiting at 1 trial location

Overseen By Jonathan D Charlesworth, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Noctrix Health, Inc.

Must be taking: Prescription opioids

Must not be taking: Antidepressants, Sleep medications

Disqualifiers: Epilepsy, Severe movement disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to assist individuals with Restless Legs Syndrome (RLS) who currently use opioids. The focus is on noninvasive peripheral nerve stimulation (NPNS), which uses a device to stimulate nerves without surgery, to determine if it reduces opioid dependence. Participants should have primary RLS affecting their legs, maintain a steady opioid dose, and manage online questionnaires and communication. Those meeting these criteria and interested in a new treatment option may find this trial suitable. As an unphased trial, it offers a unique chance to explore innovative RLS treatments without the constraints of traditional clinical trial phases.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it requires that you have been on a stable dose of prescription opioids for at least 3 months before joining the study.

What prior data suggests that this noninvasive peripheral nerve stimulation is safe for patients with RLS?

Research has shown that noninvasive peripheral nerve stimulation (NPNS) can safely treat conditions like restless legs syndrome (RLS). Studies have found that NPNS reduces symptoms by activating certain pathways in the body, leading to improved muscle activity in the legs. Importantly, NPNS provides pain relief without the common side effects of other treatments.

While more research is needed to confirm the long-term safety of NPNS for RLS, similar therapies used for other chronic conditions have been well-tolerated. Current studies suggest that NPNS is effective without causing significant side effects, making it a promising alternative to medication. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Noninvasive Peripheral Nerve Stimulation (NPNS) for Restless Legs Syndrome because it offers a unique, non-drug approach to managing symptoms, which is especially promising for those reducing opioid use. Unlike traditional medications that often come with side effects and potential for dependency, this technique uses a device to deliver electrical stimulation to nerves, aiming to provide relief without the need for pills. This method could revolutionize treatment by offering a safer, more sustainable option for patients seeking relief from restless legs without relying heavily on pharmaceuticals.

What evidence suggests that noninvasive peripheral nerve stimulation is effective for reducing opioid use in patients with RLS?

Research has shown that noninvasive peripheral nerve stimulation (NPNS), which participants in this trial will receive, can help manage pain, benefiting those with Restless Legs Syndrome (RLS). In one study, 87.6% of participants reported improved quality of life, including better sleep and mood. Another study found that 67% to 100% of patients experienced significant pain relief 12 months after using similar treatments. These findings suggest that NPNS might help relieve RLS symptoms, particularly by reducing the need for opioids. While early results are promising, further research is needed to confirm these benefits specifically for RLS. ^{3 6 7 8 9}

Who Is on the Research Team?

Jonathan D Charlesworth, PhD

Principal Investigator

Noctrix Health, Inc.

Are You a Good Fit for This Trial?

Inclusion Criteria

You possess 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 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.

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.

Exclusion Criteria

You have an ongoing condition like a severe infection, kidney disease, anemia or swelling in your lower legs.

You are allergic to the materials used for the electrodes or the clothing worn during the study.

You have Restless Leg Syndrome (RLS) that was caused by another medical condition that has already been diagnosed.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-in Phase

Participants undergo a 1-2 week run-in phase to allow resolution of opioid withdrawal symptoms unrelated to RLS

1-2 weeks

Assessment Phase

A 1-week assessment phase to evaluate if RLS symptoms have increased after opioid dose reduction

1 week

Extension Phase (optional)

Participants who tolerate both step-downs have the option of an extension phase involving a third step-down with the same format

Up to 9 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Noninvasive Peripheral Nerve Stimulation (NPNS)

How Is the Trial Designed?

Group I: Noninvasive Peripheral Nerve Stimulation (NPNS) Experimental Treatment 1 Intervention

NPNS device programmed to deliver active stimulation.

Who Is Running the Clinical Trial?

Noctrix Health, Inc.

Lead Sponsor

Trials

7

Recruited

700+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Published Research Related to This Trial

Peripheral nerve stimulation (PNS) has been effectively used since the 1960s to treat various painful conditions, showcasing its long-standing efficacy as a neuromodulation technique.

The field of PNS is rapidly evolving, with ongoing advancements in technology and procedures that enhance its clinical applications and effectiveness in pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

History of peripheral nerve stimulation. Slavin, KV.[2019]

A case study of a 53-year-old woman with chronic lower extremity neuropathic pain showed that a design-specific peripheral nerve stimulation (PNS) device provided significant pain relief and improved functionality for two years after implantation.

This case highlights the effectiveness of modern PNS technology, suggesting it may be a preferable option over spinal cord stimulation for patients with isolated extremity pain, particularly those with spinal abnormalities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advancement in Neuromodulation Technology with the Innovation of Design-Specific Peripheral Nerve Stimulators: Sural Nerve Stimulation for Radiculopathy. Langford, B., Mauck, WD.[2021]

External noninvasive peripheral nerve stimulation (EN-PNS) showed significant short-term pain relief in patients with refractory neuropathic pain, with an average reduction of 2.8 points on a numerical rating scale after treatment.

In a study of 20 patients, 40% experienced improvements in quality of life and function, indicating that EN-PNS may be a beneficial option for managing chronic pain, although further controlled studies are needed to validate these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

External Noninvasive Peripheral Nerve Stimulation Treatment of Neuropathic Pain: A Prospective Audit. Johnson, S., Ayling, H., Sharma, M., et al.[2022]

In a study of patients with chronic neuropathic pain who had previously responded to external noninvasive peripheral nerve stimulation (EN-PNS), all five participants reported continued use of the device and ongoing pain relief after an average of 3.5 years.

Pain intensity significantly decreased from an average of 5.6 to 3.5, and the worst pain reported dropped from 8.6 to 4.8, indicating that EN-PNS can provide long-term benefits for managing chronic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Treatment of Chronic Neuropathic Pain Using External Noninvasive External Peripheral Nerve Stimulation in Five Patients. Johnson, S., Goebel, A.[2022]

In a retrospective study of 46 patients with painful nerve injuries, peripheral nerve stimulation (PNS) provided good pain relief (50% or more reduction) in 78% of cases over a follow-up period of 3 to 16 years.

The average pain intensity significantly decreased from a visual analog scale (VAS) score of 69 before surgery to 24 after PNS, indicating that PNS is an effective long-term treatment option for selected patients with isolated painful neuropathies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term peripheral nerve stimulation for painful nerve injuries. Eisenberg, E., Waisbrod, H., Gerbershagen, HU.[2019]

In a retrospective case series involving 8 patients with neuropathic extremity pain, 75% of the trials for peripheral nerve stimulation (PNS) were successful, leading to permanent implantation of the PNS system.

The minimally invasive, ultrasound-assisted technique resulted in over 50% pain relief for most patients at follow-up, with some experiencing over 80% relief, demonstrating both efficacy and safety by avoiding the complications associated with traditional surgical methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound-guided permanent implantation of peripheral nerve stimulation (PNS) system for neuropathic pain of the extremities: original cases and outcomes. Huntoon, MA., Burgher, AH.[2022]

Implanting the pulse generator (IPG) closer to the lead location, such as in the infraclavicular region, significantly reduces the incidence of adverse events (AEs) related to peripheral nerve stimulation (PNS) for chronic migraine management, indicating a safer surgical approach.

Increased experience of the implanter, measured by the number of prior PNS implants performed, is associated with a lower rate of stimulation- and hardware-related AEs, suggesting that skill and precision improve with practice, leading to better patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of adverse events in the management of chronic migraine by peripheral nerve stimulation. Sharan, A., Huh, B., Narouze, S., et al.[2022]

The distal to proximal neurostimulator lead revision technique is a safe and effective method for adjusting lead positions in patients with chronic pain, as demonstrated in a case series of 3 patients.

All patients experienced over 50% pain reduction at long-term follow-up, indicating that this technique can provide significant relief without the need for replacing the entire neurostimulator system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A technique of distal to proximal revision of peripheral neurostimulator leads: technical note. Mammis, A., Mogilner, AY.[2014]

In a study of 100 patients with chronic intractable pain, peripheral nerve field stimulation (PNFS) led to an average pain reduction of 4.2 points on an 11-point scale, indicating significant efficacy in pain management.

The treatment was safe, with no long-term complications reported, and 72% of patients reduced their use of analgesics after PNFS, highlighting its potential to improve quality of life and change pain management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peripheral nerve field stimulation for chronic pain: 100 cases and review of the literature. Verrills, P., Vivian, D., Mitchell, B., et al.[2011]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11801347/

Real-world long-term outcomes of peripheral nerve stimulation Patients report clinically meaningful long-term pain relief after receiving PNS through both 60-day and permanent implant systems.

2. practicalneurology.com practicalneurology.com/news/noninvasive-peripheral-nerve-stimulation-device-may-be-effective-option-for-treating-pain/2470151/

Noninvasive Peripheral Nerve Stimulation Device May Be ... Improvements in quality of life reported in 87.6% of participants, including improvements in sleep and mood; Forty-two percent (42%) of patients ...

3. neuromodulationjournal.org neuromodulationjournal.org/article/S1094-7159(25)00138-2/fulltext

Safety and Efficacy of Magnetic Peripheral Nerve ... A systematic review reported 67% to 100% of patients experienced >50% pain relief 12 months after initiation of SCS therapy. However, SCS ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04698343

NCT04698343 | Noninvasive Peripheral Nerve Stimulation ... The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure.

5. dovepress.com dovepress.com/efficacy-and-safety-of-magnetic-peripheral-nerve-stimulation-for-treat-peer-reviewed-fulltext-article-JPR

Efficacy and Safety of Magnetic Peripheral Nerve ... Of the participants who reported improvements in pain levels, 81.3% and 84.6% of participants in the CMM + mPNS and Crossover groups reported ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05214963

Noninvasive Peripheral Nerve Stimulation for Medication- ... Prospective multi-site randomized sham-controlled study evaluating tolerability and efficacy of noninvasive peripheral nerve stimulation (NPNS) for patients ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8656897/

Noninvasive neuromodulation reduces symptoms of restless ... Although the long-term safety and tolerability of NPNS for RLS remains to be determined, neurostimulation therapies for other chronic conditions, eg, epilepsy, ...

8. jcsm.aasm.org jcsm.aasm.org/doi/10.5664/jcsm.10536

Bilateral high-frequency noninvasive peroneal nerve ... These results demonstrate that NPNS reduces RLS symptoms by activating afferent pathways, thereby generating tonic and sustained leg muscle activity without ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S1094715925001382

Safety and Efficacy of Magnetic Peripheral Nerve ... Noninvasive magnetic peripheral nerve stimulation (mPNS) provides effective pain relief without the side effects associated with interventional approaches.