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

doi:10.1093/sleep/zsad188

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. 2023 Oct 11;46(10):zsad188. doi: 10.1093/sleep/zsad188.

Authors

Asim Roy¹, Joseph Ojile², Jerrold Kram³, Jonathan Olin⁴, Russell Rosenberg⁵, J Douglas Hudson⁶, Richard K Bogan⁷, Jonathan D Charlesworth⁸

Affiliations

¹ Ohio Sleep Medicine Institute, Dublin, OH, USA.
² Clayton Sleep Institute, LLC, St. Louis, MO, USA.
³ California Center for Sleep Disorders, San Leandro, CA, USA.
⁴ Delta Waves, Inc., Colorado Springs, CO, USA.
⁵ NeuroTrials Research Inc., Atlanta, GA, USA.
⁶ FutureSearch Trials of Neurology, Austin, TX, USA.
⁷ Bogan Sleep Consultants, LLC, Columbia, SC, USA.
⁸ Noctrix Health, Inc., Department of Clinical Research, Pleasanton, CA, USA.

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.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Dopamine Agonists* / adverse effects
Double-Blind Method
Humans
Restless Legs Syndrome* / drug therapy
Severity of Illness Index
Treatment Outcome

Substances

Dopamine Agonists

Associated data

ClinicalTrials.gov/NCT05196828