Efficacy and Tolerability of Extended-Duration Tonic Motor Activation for Treatment of Restless Legs Syndrome with Awakenings During Sleep

Background: Restless legs syndrome (RLS) is a prevalent neurological sleep disorder that often impairs sleep maintenance. This single-arm, open-label study evaluated the efficacy, safety, and tolerability of extended-duration tonic motor activation (XD-TOMAC) in adults with RLS who experience frequent awakenings with symptoms. Methods: The study comprised three stages: Stage 1 (2 weeks of no intervention), Stage 2 (8 weeks XD-TOMAC), and Stage 3 (2 weeks of no intervention). XD-TOMAC consisted of bilateral high-frequency peroneal nerve stimulation programmed to 180 min duration and administered nightly at bedtime. Nineteen adults with moderate–severe RLS were enrolled, each reporting at least three nights per week of RLS symptoms causing increased awakenings or interfering with returning to sleep after waking. Results: The intent-to-treat analysis population included all patients who began Stage 2 (n = 15). After 8 weeks of XD-TOMAC, the mean change in International RLS Study Group Rating Scale (IRLS) score was −10.6 points (p < 0.001), and the mean change in Medical Outcomes Study Sleep Problems Index II (MOS-II) was −29.5 points (p < 0.001). The mean change in the number of nocturnal awakenings was −1.1 per night (p = 0.009), and the mean change in sleep efficiency was +8.5% (p = 0.001). The mean change in time awake with RLS symptoms after sleep onset was −28.1 min (p = 0.009). Each of these improvements was sustained at the end of Stage 3 (p < 0.01). There were no serious or severe device-related adverse events. Conclusions: Compared with prior 30 min TOMAC studies, XD-TOMAC demonstrated greater efficacy and similar tolerability, supporting its potential as a nonpharmacological therapy for RLS patients whose symptoms frequently disrupt sleep.