Peroneal Electrical Nerve Stimulation in Pregnancy for Restless Legs Syndrome

Not Applicable

Not yet recruiting

• Conditions: Restless Leg Disorder; Restless Leg Syndrome (RLS); Pregnancy; Sleep Disorder (Disorder)

• Registration Number: NCT07144631
• Lead Sponsor: Rhode Island Hospital

Brief Summary

The goal of this clinical trial is to learn if peroneal nerve stimulation (PNS) can be a feasible, acceptable, and safe way to treat Restless Legs Syndrome (RLS) in pregnant women. It will also gather preliminary information on whether PNS can improve sleep quality and reduce RLS symptoms in this population.

The main questions it aims to answer are:

Is PNS a feasible and acceptable treatment for RLS during pregnancy? Does PNS reduce RLS symptom severity and improve sleep quality in pregnant women? Are there any maternal, fetal, or neonatal safety concerns with PNS use in pregnancy?

Participants will:

Use a non-invasive PNS device for 30-minute sessions, up to four times per day, for 8 weeks Complete questionnaires about symptoms, sleep quality, and device use Wear an actigraphy watch to record sleep patterns Attend scheduled follow-ups for maternal and fetal health assessments

Detailed Description

This is a prospective, open-label, single-arm pilot clinical trial designed to evaluate the feasibility, acceptability, safety, and preliminary effectiveness of TOMAC™ peroneal nerve stimulation (PNS) therapy for the treatment of Restless Legs Syndrome (RLS) during pregnancy.

RLS is a common neurological condition affecting 20-30% of pregnant individuals, often worsening in the second and third trimesters. It is associated with impaired sleep quality and adverse pregnancy outcomes such as gestational hypertension, preeclampsia, prolonged labor, and increased cesarean delivery rates. Pharmacologic treatments for RLS are limited during pregnancy due to uncertain fetal safety, creating a critical need for non-pharmacologic alternatives.

The TOMAC™ device delivers high-frequency stimulation to the common peroneal nerve via an externally worn, non-invasive system. It is FDA-cleared for the treatment of moderate-to-severe RLS in adults but has not been studied in pregnancy. Safety is supported by analogous neuromodulation therapies, such as sacral nerve stimulation, which have been used during pregnancy without adverse maternal or fetal outcomes.

Primary objectives are to assess feasibility and acceptability using validated implementation measures: Acceptability of Intervention Measure (AIM), Intervention Appropriateness Measure (IAM), and Feasibility of Intervention Measure (FIM). Secondary objectives include assessing adherence, dose tolerance, usability, symptom improvement, sleep quality, and maternal-fetal safety outcomes.

Fifteen pregnant participants between 21 and 26 weeks' gestation with The International Restless Legs Syndrome Study Group-confirmed RLS will be enrolled. After baseline assessments and device titration under supervision (including uterine contraction and fetal monitoring at ≥28 weeks), participants will use the TOMAC™ device at home for 8 weeks, up to four 30-minute sessions per day, prioritizing times of symptom distress or before bedtime.

Data will be collected from patient-reported outcomes (PGI-I, PSQI, ESS, FOSQ), actigraphy, device usage logs, and maternal-fetal safety monitoring. Follow-up includes biweekly phone calls, a mid-study visit at week 4, a final visit at week 8, and a 3-month postpartum safety check.

This study will generate the first prospective safety and feasibility data for peroneal nerve stimulation in pregnancy and inform the design of a future randomized controlled trial evaluating its effectiveness in improving maternal sleep, reducing RLS symptoms, and potentially lowering the risk of adverse pregnancy outcomes.

Study Timeline

• Status Verified: 2025-08
• Study First Submitted: 2025-08-11
• Study First Submitted QC: 2025-08-20
• Last Update Submitted: 2025-08-20
• Study First Posted: 2025-08-27
• Last Update Posted: 2025-08-27
• Study Start: 2025-10-01
• Primary Completion: 2026-09-30
• Study Completion: 2026-10-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 15

Inclusion Criteria

• Age ≥18 years
• Pregnant individuals between 21 and 26 weeks' gestation at enrollment
• Singleton pregnancy without known fetal anomalies
• Confirmed clinical diagnosis of Restless Legs Syndrome (RLS) according to International Restless Legs Syndrome Study Group (IRLSSG) criteria, confirmed by a sleep medicine specialist to exclude RLS mimics
• Serum ferritin ≥75 µg/L and transferrin saturation ≥20% within 2 months prior to enrollment
• Able and willing to provide informed consent
• Able and willing to comply with study procedures, including device usage, questionnaires, adherence diaries, and follow-up assessments up to 3 months postpartum

Exclusion Criteria

Pregnancy-related:

• History of preterm labor
• Known fetal anomalies identified prior to enrollment

Neurological and neuromuscular disorders:

• Pre-existing neuromuscular disorders affecting balance or gait
• Severe peripheral neuropathy involving the lower legs
• Epilepsy or history of seizures

Cardiovascular and circulatory conditions:

• History of deep vein thrombosis (DVT)
• Circulatory conditions contraindicating peroneal nerve stimulation (PNS) device use

Dermatological conditions:

• Skin conditions at device application sites
• Known allergy to device materials

Other sleep disorders:

• Inadequately treated severe primary sleep disorders other than RLS (e.g., untreated severe sleep apnea, severe insomnia unrelated to RLS)

Device and treatment experience exclusions (based on RESTFUL trial criteria):

• Prior use of the study device or any neurostimulation device for RLS treatment
• Presence of active medical implants (e.g., pacemakers, spinal cord stimulators)

Other medical conditions:

• Participants undergoing dialysis treatment
• Severe psychiatric conditions (e.g., bipolar disorder, psychosis, severe anxiety or depression) that may interfere with adherence or accurate symptom reporting
• Any condition deemed by investigators to pose safety risks or impede participation

Other exclusions:

• Unable or unwilling to operate the device safely and independently
• Unable to participate reliably in follow-up assessments or complete self-reported diaries

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Acceptability of Intervention Measure (AIM) Score	Baseline to 8 weeks of intervention	The Acceptability of Intervention Measure (AIM) is a validated 4-item questionnaire assessing participants' perceptions of how acceptable the intervention is. Scores range from 1 to 5. Higher scores indicate greater acceptability.
Intervention Appropriateness Measure (IAM) Score	Baseline and Week 8 of intervention	The Intervention Appropriateness Measure (IAM) is a validated 4-item questionnaire assessing participants' perceptions of how appropriate the intervention is for their condition. Scores range from 1 to 5. Higher scores indicate greater appropriateness.
Feasibility of Intervention Measure (FIM) Score	Baseline and Week 8 of intervention	The Feasibility of Intervention Measure (FIM) is a validated 4-item questionnaire assessing participants' perceptions of how feasible it is to use the intervention. Scores range from 1 to 5. Higher scores indicate greater feasibility.

Secondary Outcome Measures

Name	Time	Method
Change in International Restless Legs Syndrome Rating Scale (IRLS) Score	Baseline, Week 4, Week 8	The International Restless Legs Syndrome Rating Scale (IRLS) is a validated 10-item questionnaire measuring symptom severity. Scores range from 0 to 40, with higher scores indicating more severe symptoms. Results will be reported as mean change in score.
Patient Global Impression of Improvement (PGI-I) Score	Week 4, Week 8	The Patient Global Impression of Improvement (PGI-I) is a validated 1-item patient-reported measure of perceived improvement. Scores range from 1 to 7, with lower scores indicating greater improvement. Results will be reported as distribution of scores.
Change in Pittsburgh Sleep Quality Index (PSQI) Score	Baseline, Week 4, Week 8	The Pittsburgh Sleep Quality Index (PSQI) is a validated 19-item questionnaire assessing subjective sleep quality. Global scores range from 0 to 21, with higher scores indicating worse sleep quality. Results will be reported as mean change in score.
Adherence to Maximum Allowed Device Sessions	Throughout 8 weeks of intervention	Adherence will be measured as the proportion of actual device sessions used compared to the maximum allowed use (up to four 30-minute sessions per day for 8 weeks). Data will be collected from device logs and participant diaries. Results will be reported as the percentage of completed sessions relative to the maximum allowable sessions.
Mean Session Duration	Continuous during 8-week intervention	Average duration of each stimulation session, recorded by device logs. Results will be reported in minutes per session.
Mean Stimulation Voltage Used During Device Sessions	Continuous during 8-week intervention	Average stimulation voltage delivered by the peroneal nerve stimulation (PNS) device during participant sessions, recorded from device logs. Results will be reported as mean voltage across all sessions.
Number of Participants With Treatment-Related Adverse Events (AEs)	Throughout 8-week intervention	Number of participants experiencing treatment-emergent adverse events related to device use, as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Results will be reported as total number of participants.
Number of Participants With Serious Adverse Events (SAEs)	Throughout 8-week intervention	Number of participants experiencing serious adverse events related to device use, as assessed by CTCAE v4.0. Results will be reported as total number of participants.
Change in Maternal Systolic Blood Pressure	Baseline, Week 4, Week 8	Maternal systolic blood pressure measured at in-clinic visits using automated sphygmomanometer. Results will be reported as mean change in millimeters of mercury (mmHg).
Change in Maternal Diastolic Blood Pressure	Baseline, Week 4, Week 8	Maternal diastolic blood pressure measured at in-clinic visits using automated sphygmomanometer. Results will be reported as mean change in millimeters of mercury (mmHg).
Change in Maternal Heart Rate	Baseline, Week 4, Week 8	Maternal heart rate measured at in-clinic visits using automated sphygmomanometer. Results will be reported as mean change in beats per minute (bpm).
Incidence of Uterine Irritability During Titration	At ≥28 weeks of pregnancy during titration session	Proportion of participants who experience uterine irritability during the in-clinic titration session (≥28 weeks gestation). Uterine irritability is defined per protocol as ≥10 contractions within a 20-minute period, measured using external tocodynamometry. Results will be reported as percentage of participants.
Incidence of Fetal Distress During Titration	At ≥28 weeks of pregnancy during titration session	Proportion of participants who experience fetal distress during the in-clinic titration session (≥28 weeks gestation). Fetal distress is defined as one or more of the following: * FHR bradycardia \<110 bpm for ≥10 minutes; * FHR tachycardia \>160 bpm for ≥10 minutes; * Minimal/absent variability (\<5 bpm amplitude for ≥20 minutes); * Recurrent decelerations (≥3 late or variable decelerations in 20 minutes); Results will be reported as percentage of participants.
Incidence of Uterine Irritability Associated With Fetal Distress	At ≥28 weeks of pregnancy during titration session	Proportion of participants who experience both uterine irritability (≥10 contractions in 20 minutes) and concurrent fetal distress during the same titration session, as defined above. Results will be reported as percentage of participants.
Change in Daytime Sleepiness	Baseline, Week 4, Week 8	Change in daytime sleepiness as measured by the Epworth Sleepiness Scale (ESS). Scores range from 0 to 24, with higher scores indicating greater daytime sleepiness.
Change in Functional Outcomes of Sleep (FOSQ-10)	Baseline, Week 4, Week 8	Change in functional outcomes related to sleep measured by the Functional Outcomes of Sleep Questionnaire (FOSQ-10). Scores range from 5 to 20, with higher scores indicating better functional status.
Infant Birth Weight	At delivery	Infant birth weight measured at delivery. Results will be reported in grams.
Neonatal Apgar Score at 1 Minute	At delivery (1 minute)	Neonatal Apgar score assessed at 1 minute after delivery. Scores range from 0 to 10, with higher scores indicating better neonatal condition. Results will be reported as mean score.
Neonatal Apgar Score at 5 Minutes	At delivery (5 minutes)	Neonatal Apgar score assessed at 5 minute after delivery. Scores range from 0 to 10, with higher scores indicating better neonatal condition. Results will be reported as mean score.
Neonatal Health Outcomes at 3 Months Postpartum	3 months postpartum	Proportion of infants with adverse health outcomes, including but not limited to growth restriction, feeding difficulties, recurrent hospitalizations, or clinician-diagnosed developmental concerns. Outcomes will be reported as percentage of infants, based on maternal report confirmed by pediatric/OB medical records.

Trial Locations

Locations (1)

Rhode Island Hospital; 🇺🇸 Providence, Rhode Island, United States