Peroneal Electrical Nerve Stimulation in Pregnancy for Restless Legs Syndrome

Официальное название

PENS-P: Peroneal Electrical Nerve Stimulation in Pregnancy for Restless Legs Syndrome (RLS)

Обзор

The goal of this study is to evaluate whether peroneal electrical nerve stimulation (PNS) using the TOMAC™ device is a feasible, acceptable, and safe non-pharmacologic intervention for managing Restless Legs Syndrome (RLS) during pregnancy. This pilot study will also collect preliminary information on symptom relief, sleep quality, and maternal-fetal safety associated with device use. The main questions the study aims to answer are: Is TOMAC™ PNS a feasible and acceptable intervention for RLS in pregnant individuals? Are there any maternal, fetal, or neonatal safety concerns with PNS use during pregnancy? What are the patterns of adherence, tolerance, and usability of the TOMAC™ device in this population? Participants will: Use a non-invasive TOMAC™ peroneal nerve stimulator during 30-minute sessions as needed, for 8 weeks. Complete questionnaires assessing feasibility, acceptability, symptom severity, and sleep quality (including AIM, IAM, FIM, IRLS, PGI-I, PSQI, ESS, FOSQ, and MOS-II). Wear an actigraphy monitor to collect objective sleep data at baseline and at 4 weeks. Attend scheduled follow-up visits and phone check-ins for maternal vital signs, uterine contraction and fetal monitoring, and neonatal outcome assessment. This is a prospective, open-label, single-arm pilot study enrolling 15 pregnant participants between 21 and 26 weeks' gestation. Findings will provide the first dataset on the feasibility, acceptability, and safety of TOMAC™ PNS in pregnancy and inform the design of a future randomized controlled trial.

Подробное описание

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

RLS affects approximately 20-30% of pregnant individuals, with symptoms often worsening during the second and third trimesters. It is associated with disrupted sleep, decreased quality of life, and adverse pregnancy outcomes such as gestational hypertension, preeclampsia, prolonged labor, and increased cesarean delivery rates. Pharmacologic therapies for RLS are generally avoided during pregnancy because of limited data on fetal safety, highlighting the need for effective, non-pharmacologic alternatives.

The TOMAC™ system is a non-invasive, wearable, high-frequency peroneal nerve stimulator that delivers bilateral stimulation to the common peroneal nerves. It is FDA De Novo granted for use in adults with moderate to severe RLS but has not been evaluated in pregnant populations. Safety rationale for this study is informed by evidence from other neuromodulation therapies, such as sacral nerve stimulation, which have been used safely during pregnancy without observed maternal or fetal harm.

Primary objectives are to evaluate the feasibility and acceptability of TOMAC™ PNS using validated implementation measures, including the Acceptability of Intervention Measure (AIM), Intervention Appropriateness Measure (IAM), and Feasibility of Intervention Measure (FIM).

Secondary objectives include assessment of adherence, dose tolerance, usability, maternal and fetal safety, and exploratory evaluation of symptom improvement and sleep quality through the International Restless Legs Syndrome Rating Scale (IRLS), Patient Global Impression of Improvement (PGI-I), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire (FOSQ), and Medical Outcomes Study Sleep Problem Index II (MOS-II).

Fifteen pregnant individuals between 21 and 26 weeks of gestation with a confirmed diagnosis of RLS will be enrolled. Following baseline assessments, participants will undergo an in-person titration session under clinical supervision, which includes uterine contraction and fetal monitoring performed at ≥28 weeks' gestation to ensure maternal and fetal safety.

Participants will then use the TOMAC™ device at home for an 8-week intervention, performing self-administered 30-minute sessions as needed, preferably during periods of symptom distress or prior to sleep.

Data will be collected from patient-reported outcomes, actigraphy sleep recordings, device usage logs, and maternal-fetal safety monitoring. Follow-up includes biweekly phone check-ins, an in-person mid-study visit at week 4, a final in-person visit at week 8, and a three-month postpartum safety follow-up.

This pilot study will generate the first prospective data on the feasibility, acceptability, and safety of peroneal nerve stimulation in pregnancy, providing foundational evidence for future randomized controlled trials evaluating TOMAC™ PNS as a pregnancy-safe, non-pharmacologic treatment for RLS and its potential to improve maternal sleep and pregnancy outcomes.

Вмешательства

• Устройство Peroneal Nerve Stimulation (PNS) Device
  The TOMAC™ system is a non-invasive, wearable peroneal nerve stimulator that delivers high-frequency electrical stimulation to the common peroneal nerves at the fibular head. It is FDA-cleared for the treatment of moderate-to-severe Restless Legs Syndrome (RLS) in adults but has not been studied in pregnancy. In this trial, pregnant participants will undergo an in-clinic titration session with uterine contraction and fetal monitoring at ≥28 weeks' gestation to determine comfortable therapeutic i

Первичные конечные точки

• Acceptability of Intervention Measure (AIM) Score [Срок оценки: Baseline to 8 weeks of intervention]
• Intervention Appropriateness Measure (IAM) Score [Срок оценки: Baseline and Week 8 of intervention]
• Feasibility of Intervention Measure (FIM) Score [Срок оценки: Baseline and Week 8 of intervention]

Вторичные конечные точки (12)

• Adherence to Maximum Allowed Device Sessions [Срок оценки: Throughout 8 weeks of intervention]
• Mean Session Duration [Срок оценки: Continuous during 8-week intervention]
• Mean Stimulation Voltage Used During Device Sessions [Срок оценки: Continuous during 8-week intervention]
• Number of Participants With Treatment-Related Adverse Events (AEs) [Срок оценки: Throughout 8-week intervention]
• Number of Participants With Serious Adverse Events (SAEs) [Срок оценки: Throughout 8-week intervention]
• Change in Maternal Systolic Blood Pressure [Срок оценки: Baseline, Week 4, Week 8]
• Change in Maternal Diastolic Blood Pressure [Срок оценки: Baseline, Week 4, Week 8]
• Change in Maternal Heart Rate [Срок оценки: Baseline, Week 4, Week 8]
• Incidence of Uterine Irritability During Titration [Срок оценки: At ≥28 weeks of pregnancy during titration session]
• Incidence of Fetal Distress During Titration [Срок оценки: At ≥28 weeks of pregnancy during titration session]
• Incidence of Uterine Irritability Associated With Fetal Distress [Срок оценки: At ≥28 weeks of pregnancy during titration session]
• Infant Birth Weight [Срок оценки: At delivery]

Критерии участия

Критерии включения

• 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
• 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

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 2 центра

• Rhode Island Hospital — Providence
• Rhode Island Hospital — Providence

Публикации

• Yoshimura C, Arima H, Amagase H, Takewaka M, Nakashima K, Imaoka C, Miyanaga N, Obama H, Fujita M, Ando SI. Idiopathic and secondary restless legs syndrome during pregnancy in Japan: Prevalence, clinical features and delivery-related outcomes. PLoS One. 2021 May 11;16(5):e0251298. doi: 10.1371/journal.pone.0251298. eCollection 2021. PMID 33974646
• Yaiesh SM, Al-Terki AE, Al-Shaiji TF. Safety of Sacral Nerve Stimulation in Pregnancy: A Literature Review. Neuromodulation. 2016 Oct;19(7):770-779. doi: 10.1111/ner.12450. Epub 2016 Jun 10. PMID 27286484
• Winkelman JW, Berkowski JA, DelRosso LM, Koo BB, Scharf MT, Sharon D, Zak RS, Kazmi U, Falck-Ytter Y, Shelgikar AV, Trotti LM, Walters AS. Treatment of restless legs syndrome and periodic limb movement disorder: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2025 Jan 1;21(1):137-152. doi: 10.5664/jcsm.11390. PMID 39324694
• Weiner BJ, Lewis CC, Stanick C, Powell BJ, Dorsey CN, Clary AS, Boynton MH, Halko H. Psychometric assessment of three newly developed implementation outcome measures. Implement Sci. 2017 Aug 29;12(1):108. doi: 10.1186/s13012-017-0635-3. PMID 28851459
• Walters AS, LeBrocq C, Dhar A, Hening W, Rosen R, Allen RP, Trenkwalder C; International Restless Legs Syndrome Study Group. Validation of the International Restless Legs Syndrome Study Group rating scale for restless legs syndrome. Sleep Med. 2003 Mar;4(2):121-32. doi: 10.1016/s1389-9457(02)00258-7. PMID 14592342
• Vahdat M, Sariri E, Miri S, Rohani M, Kashanian M, Sabet A, Zamani B. Prevalence and associated features of restless legs syndrome in a population of Iranian women during pregnancy. Int J Gynaecol Obstet. 2013 Oct;123(1):46-9. doi: 10.1016/j.ijgo.2013.04.023. Epub 2013 Jul 22. PMID 23886452
• Teresi JA, Yu X, Stewart AL, Hays RD. Guidelines for Designing and Evaluating Feasibility Pilot Studies. Med Care. 2022 Jan 1;60(1):95-103. doi: 10.1097/MLR.0000000000001664. PMID 34812790
• Szymanski JK, Slabuszewska-Jozwiak A, Jakiel G. Sacral Neuromodulation in Pregnant Women-A Case Report and Literature Review. Int J Environ Res Public Health. 2022 Jul 8;19(14):8340. doi: 10.3390/ijerph19148340. PMID 35886191

Идентификаторы

NCT: NCT07144631 · 2313348

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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