Long-term efficacy and safety of tonic motor activation for treatment of medication-refractory restless legs syndrome: A 24-Week Open-Label Extension Study.

STUDY OBJECTIVES: To evaluate long-term efficacy and safety of tonic motor activation (TOMAC) for treatment of medication-refractory moderate-to-severe primary restless legs syndrome (RLS). METHODS: In the parent study (RESTFUL), adults with refractory RLS were randomized to active TOMAC or sham for 4 weeks followed by 4 weeks of open-label active TOMAC. In the extension study, earlier RESTFUL completers comprised the control group (n = 59), which was followed for 24 weeks with no TOMAC intervention, and later RESTFUL completers compromised the treatment group (n = 44), which received 24 additional weeks of open-label active TOMAC followed by no intervention for 8 weeks. The primary endpoint was Clinician Global Impressions-Improvement (CGI-I) responder rate at week 24 compared to RESTFUL entry. RESULTS: CGI-I responder rate improved from 63.6% (95% CI, 49.4 to 77.9%) at RESTFUL completion to 72.7% (95% CI, 58.2 to 83.7%) at week 24 for the treatment group versus 13.6% (95% CI, 7.0 to 24.5%) at week 24 for the control group (p < 0.0001). Mean change in International RLS Rating Scale (IRLS) score improved from -7.4 (95% CI, -5.6 to -9.2) at RESTFUL completion to -11.3 points (95% CI, -8.8 to -13.9) at week 24 for the treatment group versus -5.4 (95% CI, -3.7 to -7.2) at week 24 for control group (p = 0.0001). All efficacy endpoints partially reverted during cessation of treatment. There were no grade 2 or higher device-related adverse events. CONCLUSIONS: TOMAC remained safe and efficacious for >24 total weeks of treatment with partial reversion of benefits upon cessation. CLINICAL TRIAL: Extension Study Evaluating NTX100 Neuromodulation System for Medication-Refractory Primary RLS; clinicaltrials.gov/ct2/show/NCT05196828; Registered at ClinicalTrials.gov with the identifier number NCT05196828.

Efficacy and safety of tonic motor activation (TOMAC) for medication-refractory restless legs syndrome: a randomized clinical trial.

STUDY OBJECTIVES: The purpose of this study was to evaluate the efficacy and safety/tolerability of bilateral high-frequency tonic motor activation (TOMAC) in patients with medication-refractory restless legs syndrome (RLS). METHODS: RESTFUL was a multicenter, randomized, double-blind, sham-controlled trial in adults with medication-refractory moderate-to-severe primary RLS. Participants were randomized 1:1 to active or sham TOMAC for a double-blind, 4-week stage 1 and all received active TOMAC during open-label, 4-week stage 2. The primary endpoint was the Clinical Global Impressions-Improvement (CGI-I) responder rate at the end of stage 1. Key secondary endpoints included change to International RLS Study Group (IRLS) total score from study entry to the end of stage 1. RESULTS: A total of 133 participants were enrolled. CGI-I responder rate at the end of stage 1 was significantly greater for the active versus sham group (45% vs. 16%; Difference = 28%; 95% CI 14% to 43%; p = .00011). At the end of stage 2, CGI-I responder rate further increased to 61% for the active group. IRLS change at the end of stage 1 improved for the active versus sham group (-7.2 vs. -3.8; difference = -3.4; 95% CI -1.4 to -5.4; p = .00093). There were no severe or serious device-related adverse events (AEs). The most common AEs were mild discomfort and mild administration site irritation which resolved rapidly and reduced in prevalence over time. CONCLUSIONS: TOMAC was safe, well tolerated, and reduced symptoms of RLS in medication-refractory patients. TOMAC is a promising new treatment for this population. CLINICAL TRIAL: Noninvasive Peripheral Nerve Stimulation for Medication-Refractory Primary RLS (The RESTFUL Study); clinicaltrials.gov/ct2/show/NCT04874155; Registered at ClinicalTrials.gov with the identifier number NCT04874155.

Assessment of the effects of lacosamide on sleep parameters in healthy subjects.

PURPOSE: Seizures and antiepileptic drugs (AED) may disrupt sleep patterns in patients with epilepsy, thus evaluation of lacosamide effects on objective and subjective sleep measures is warranted. METHODS: A multicenter, interventional, open-label study (NCT01530386) was conducted in healthy subjects without confounding effects of concomitant AED use, co-morbidities, or disease state to determine whether lacosamide impacts sleep parameters after 22 days of lacosamide exposure. After overnight polysomnography (PSG) to assess baseline parameters, lacosamide was initiated at 100mg/day (50mg twice daily) and increased by 100mg/day weekly to 300 mg/day (the mid-range maintenance dose for adjunctive therapy). The primary variable was change from baseline to post-treatment in wake after sleep onset (WASO). Secondary variables included additional objective sleep measures, subject-reported measures of sleep quality, daytime sleepiness, and tolerability. Change from baseline in WASO was analyzed using the Wilcoxon rank-sum test. RESULTS: A total of 27 subjects received ≥1 dose of lacosamide and 25 subjects completed the study. For WASO, median change from baseline was a 6-min reduction (95% confidence interval: -38, 77.5; p=0.1074) after lacosamide treatment; this was considered not clinically relevant. No clinically relevant changes were observed in any secondary variables. Thirteen subjects (48%) reported a treatment-emergent adverse event, none of which was severe or led to study discontinuation. CONCLUSION: Lacosamide 300 mg/day had no effect on objective or subjective sleep parameters in healthy subjects and was generally well tolerated.