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Randomized Controlled Trial
. 2023 Oct 11;46(10):zsad190.
doi: 10.1093/sleep/zsad190.

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

Richard K Bogan  1 , Asim Roy  2 , Jerrold Kram  3 , Joseph Ojile  4 , Russell Rosenberg  5 , J Douglas Hudson  6 , H Samuel Scheuller  7 , John W Winkelman  8 , Jonathan D Charlesworth  9
Affiliations
Randomized Controlled Trial

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

Richard K Bogan et al. Sleep. .

Abstract

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.

Keywords: bioelectronic; neurological disorder; neuromodulation; peripheral nerve stimulation; restless legs syndrome; sleep disorder.

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Figures

Graphical Abstract
Graphical Abstract
Figure 1.
Figure 1.
Investigational TOMAC system. (A) The investigational TOMAC system consists of two therapy units corresponding to the Right (R) and Left (L) legs. The exploded view illustrates the components of each therapy unit, consisting of the (1) compressive conduction garment outer side, (2) HF-TOMAC module, which includes the programmable pulse generator, user controls, and rechargeable battery, (3) compressive conduction garment leg-facing side, and (4) charge dispersing interface, which conducts electricity from the HF-TOMAC module to the leg and is shown in an exploded view including disposable protective liners on both sides. (B) The compressive conduction garment of each therapy unit includes the following components (1) Charge port for the rechargeable battery, (2) Intensity lights indicating the stimulation level relative to the titrated value, (3) Status light indicating stimulation and charging status, and (4) Control buttons used to turn therapy on and off and to adjust the stimulation level relative to the titrated value. (C) Depiction of (1) TOMAC therapy unit, shown in light gray, worn so that the (2) charge dispersing interfaces, shown in dark gray, are positioned over the (3) peroneal nerve near (4) the head of the fibula bone.
Figure 2.
Figure 2.
Enrollment, randomization, and treatment.
Figure 3.
Figure 3.
Comparison of Efficacy Endpoints between TOMAC and Sham. Comparison of response to TOMAC and Sham assessed at Week 4 compared to baseline for the following efficacy endpoints: A. CGI-I responder rate, B. PGI-I responder rate, C. IRLS total score, D. MOS-II score, E. MOS-I score, F. CGI-I mean score. Error bars represent standard error of means and proportions.
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Comment in

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