Tonic motor activity (TOMAC) demonstrated both safety and effectiveness throughout 24 weeks of treatment in patients with medication refractory moderate-to-severe primary restless leg syndrome (RLS); although some benefits were lost after discontinuation, according to study findings published in the journal Sleep.
Researchers conducted an open-label extension of the Noninvasive Peripheral Nerve Stimulation for Medication-Refractory Primary RLS (RESTFUL study; ClinicalTrials.gov Identifier: NCT04874155) and reported on the long-term safety and efficacy of TOMAC treatment for medication-refractory moderate-to-severe primary RLS.
In the current study, Extension Study Evaluating NTX100 Neuromodulation System for Medication-Refractory Primary RLS (RESTFUL Study Extension; ClinicalTrials.gov Identifier: NCT05196828), all participants of the RESTFUL study were eligible to be included unless they failed to comply with study requirements.
To be enrolled in the treatment group, participants were seamlessly transitioned, ensuring their uninterrupted access to ongoing TOMAC treatment. The treatment group underwent 24 weeks of active TOMAC treatment (weeks 1-24) followed by an 8-week period without TOMAC treatment (weeks 24-32) to assess the response of discontinuing TOMAC treatment.
Participants who finished the RESTFUL study before the extension study started at a specific site or who didn’t agree to be in the treatment group were qualified for the control group. The control group underwent 24 weeks of standard care without any intervention from TOMAC.
The primary endpoint was to evaluate the responder rate of Clinician Global Impressions-Improvement (CGII) at week 24, in comparison to the RESTFUL study. The responder rate was defined as the ratio of responses categorized as “Much Improved” or “Very Much Improved” compared with the baseline on the investigator-rated 7-point CGI-I scale.
A total of 51 participants from the RESTFUL study were directly transferred to the treatment group, with 45 (88%) providing consent and 44 ultimately being enrolled. Additionally, the control group consisted of 75 RESTFUL study completers, where symptom evaluation was conducted without any intervention. Out of these, 59 participants consented and were enrolled.
The baseline characteristics of both cohorts were comparable, with the majority of individuals being women and of White, non-Hispanic ethnicity. The average age of participants was 57, and they had been experiencing symptoms of RLS for an average duration of 22 years.
The rate of positive responses on the CGI-I scale showed improvement from 63.6% (95% CI, 49.4%-77.9%) at the completion of RESTFUL to 72.7% (95% CI, 58.2%-83.7%) at week 24 for the treatment group. In comparison, the control group only showed a response rate of 13.6% (95% CI, 7.0-24.5%) at week 24.
The mean change in the international RLS rating scale (IRLS) score demonstrated improvement from -7.4 (95% CI, -5.6 to -9.2) at the completion of RESTFUL to -11.3 points (95% CI, -8.8 to -13.9) at week 24 for the treatment group. In comparison, the control group had a change of -5.4 (95% CI, -3.7 to -7.2) at week 24 (P =.0001).
No significant or severe adverse events related to the device were observed. None of the participants withdrew from the study due to adverse events. The most common category of adverse events, experienced by more than 5% of participants, was discomfort, reported by 3 participants (6.8%).
The researchers wrote, “TOMAC is a promising, non-invasive long-term treatment for medication-refractory moderate-to-severe primary RLS.” “TOMAC has the potential to provide strong and durable efficacy at very low risk to this difficult-to-treat patient population and serve as a favorable alterative to off-label opioids,” they concluded.
Disclosures: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see original source for full list of disclosures.
Roy A, Ojile J, Kram J, et al. Long-term efficacy and safety of tonic motor activation for treatment of medication-refractory restless legs syndrome: a 24-week open-label extension study. Sleep. Published online July 13, 2023. doi.org/10.1093/sleep/zsad188