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

Asim Roy, Joseph Ojile, Jerrold Kram, Jonathan Olin, Russell Rosenberg, J Douglas Hudson, Richard K Bogan, Jonathan D Charlesworth, Asim Roy, Joseph Ojile, Jerrold Kram, Jonathan Olin, Russell Rosenberg, J Douglas Hudson, Richard K Bogan, Jonathan D Charlesworth

Abstract

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.

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

© The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society.

Figures

Graphical Abstract
Graphical Abstract
Figure 1.
Figure 1.
Anatomical Positioning of TOMAC Therapy Unit. Depiction of a (1) TOMAC therapy unit attached to the right leg, with (2) charge-dispersing interfaces positioned over the (3) peroneal nerve, distal to the (4) head of the fibula. The TOMAC system consists of two therapy units, one attached to each leg.
Figure 2.
Figure 2.
Participant disposition.
Figure 3.
Figure 3.
Efficacy results for the intervention and control groups. For each efficacy outcome measure, results are shown at weeks 0, 8, 16, 24, and 32 after entry into the extension study. Results are presented as responder rates relative to baseline for (A) CGI-I and (B) PGI-I and presented as mean scores for (C) IRLS total, (D) IRLS Question 7, (E) MOS-II, and (F) MOS-I. Treatment group data are shown in blue with triangle markers and bold data labels. Control group data are shown in black with square markers and data labels in italics. For both treatment and control groups, solid lines represent periods with TOMAC, and dashed lines represent periods with no intervention. Error bars represent +/− standard error.
Figure 4.
Figure 4.
Patient-administered TOMAC Intensity. Each point represents mean patient-administered TOMAC intensity for all treatment group participants (n = 44) for a given week in the RESTFUL (parent) study and extension study. Vertical dashed line indicates entry to the extension study. Error bars are +/− SEM.

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Source: PubMed

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