Developing closed-loop tonic motor activation therapy for treatment of refractory restless legs syndrome

Summary: Restless Legs Syndrome (RLS) is a prevalent and debilitating sleep disorder that affects a significant portion of the adult population, leading to considerable sleep deprivation and a reduction in quality of life. Current treatments for RLS provide mixed results and, in the case of medications, undesirable side effects. The need for innovative solutions is clear. The Noctrix Tonic Motor Activation system (TOMAC) represents a novel approach to RLS management through non-invasive peripheral nerve stimulation, offering a promising alternative to tradi- tional therapies. Despite the success of TOMAC 1.0 in reducing RLS symptoms, challenges remain in reducing sleep fragmentation and facilitating medication reduction. The proposed SBIR Phase IIB project aims to develop and clinically validate a closed-loop version of TOMAC (CL-TOMAC) to address these unmet needs. CL-TOMAC will use leg movement detection algorithms developed in the prior SBIR Phase II to automatically activate therapy during sleep to reduce wake after sleep onset (WASO). Additionally, CL-TOMAC will facilitate reduction in the dosage of common RLS medications (dopaminergics and opioids), alleviating the side effects associated with long-term medication use. The project is structured around three Specific Aims: 1) Develop and verify a closed- loop stimulation algorithm that is sensitive and specific in detecting the need for activation during sleep, 2) Assess the feasibility of CL-TOMAC in reducing WASO in patients with refractory RLS, and 3) Evaluate the potential of CL-TOMAC to facilitate reductions in common RLS medication dosages. Success will be measured through rigorous clinical and technical validation processes, including polysomnography, actigraphy, and medication dos- age assessments. By addressing these critical challenges, CL-TOMAC promises to improve health outcomes and enhance quality of life for those affected by RLS. Following successful completion, the results of Aims 2-3 will determine the intended use for CL-TOMAC (expanded to include medication reduction and/or reduced WASO), guide the design of a pivotal trial for FDA clearance, and inform the choice of patient populations to target in the commercialization strategy.