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Randomized Controlled Trial
. 2024 Oct:122:141-148.
doi: 10.1016/j.sleep.2024.08.017. Epub 2024 Aug 18.

Efficacy and safety of TOMAC for treatment of medication-naïve and medication-refractory restless legs syndrome: A randomized clinical trial and meta-analysis

Haramandeep Singh  1 , Fiona C Baker  2 , Joseph Ojile  3 , Bahman Adlou  4 , Viktoriia Kolotovska  4 , Stephanie K Rigot  4 , Jonathan D Charlesworth  5
Affiliations
Randomized Controlled Trial

Efficacy and safety of TOMAC for treatment of medication-naïve and medication-refractory restless legs syndrome: A randomized clinical trial and meta-analysis

Haramandeep Singh et al. Sleep Med. 2024 Oct.

Abstract

Objective/background: There is a significant unmet need for safe and effective nonpharmacological therapies for restless legs syndrome (RLS). The objective was to evaluate the efficacy and safety of tonic motor activation (TOMAC) in patients with RLS.

Patients/methods: A multicenter, randomized, participant-blinded, sham-controlled trial enrolled 45 adults with primary moderate-to-severe RLS who were either medication-naïve (n = 20) or medication-refractory (n = 25). Participants were 1:1 randomized to TOMAC (n = 22) or sham (n = 23) for two weeks and instructed to self-administer 30-min TOMAC sessions when they experienced RLS symptoms. The primary outcome was mean change in International RLS Study Group Rating Scale (IRLS) total score. A subsequent meta-analysis included the present trial and a previous randomized clinical trial that enrolled medication-naïve RLS patients.

Results: IRLS reduction was significantly greater for TOMAC than sham (TOMAC -6.59 vs. sham -2.17; mean difference (MD) = -4.42; 95 % confidence interval [CI] -1.57 to -7.26; p = 0.0040). Subgroup analysis showed similar IRLS mean difference for medication-refractory (MD = -4.50; p = 0.02) and medication-naïve (MD = -4.40; p = 0.08) cohorts, which was significantly different from sham only for the medication-refractory cohort. Meta-analysis of combined data from 33 medication-naïve RLS patients showed a significant reduction in mean IRLS score after two weeks for TOMAC compared to sham (MD = -4.30; 95 % CI -1.36 to -7.24; p = 0.004).

Conclusions: The present trial confirmed previous reports documenting efficacy and safety of TOMAC in refractory RLS and indicated similar effect sizes in refractory versus naïve subgroups. The meta-analysis demonstrated that TOMAC significantly improves RLS symptoms in naïve participants.

Keywords: Bioelectronic; Neurological disorder; Neuromodulation; Peripheral nerve stimulation; Restless legs syndrome; Sleep disorder.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Haramandeep Singh reports financial support and equipment, drugs, or supplies were provided by Noctrix Health, Inc. (United States). Fiona C. Baker reports financial support and equipment, drugs, or supplies were provided by Noctrix Health, Inc. Joseph Ojile reports financial support and equipment, drugs, or supplies were provided by Noctrix Health, Inc. Jonathan D. Charlesworth reports financial support was provided by National Institute of Neurological Disorders and Stroke (United States). Joseph Ojile reports a relationship with Noctrix Health, Inc. that includes: funding grants. Haramandeep Singh reports a relationship with Noctrix Health, Inc. that includes: consulting or advisory and funding grants. Jonathan D. Charlesworth reports a relationship with Noctrix Health, Inc. that includes: employment, equity or stocks, and travel reimbursement. Viktoriia Kolotovska reports a relationship with Noctrix Health, Inc. that includes: employment, equity or stocks, and travel reimbursement. Bahman Adlou reports a relationship with Noctrix Health, Inc. that includes: employment, equity or stocks, and travel reimbursement. Stephanie K. Rigot reports a relationship with Noctrix Health, Inc. that includes: employment, equity or stocks, and travel reimbursement. Jonathan D. Charlesworth has patent issued to Noctrix Health, Inc. Jonathan D. Charlesworth has patent pending to Noctrix Health, Inc. Stephanie K. Rigot has patent pending to Noctrix Health, Inc. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Figure 1.
Figure 1.
Disposition of participants
Figure 2.
Figure 2.. Meta-Analysis of IRLS Score for TOMAC Versus Sham
Abbreviations: CI, confidence interval; IRLS, International Restless Legs Syndrome Study Group Rating Scale; TOMAC, tonic motor activation.
Figure 3.
Figure 3.. Meta-Analysis of PGI-I Responder Rate for TOMAC Versus Sham
Abbreviations: CI, confidence interval; PGI-I, patient global impressions of improvement; TOMAC, tonic motor activation.
See this image and copyright information in PMC

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