Spinal Cord Neuromodulation Outcomes in Restless Legs Syndrome (NO-RLS)

/ABSTRACT Restless legs syndrome (RLS) is prevalent and growing disease that causes a significant decrease in quality of life for many patients. These patients chronically suffer from a strong urge to move their leg that particularly worsens in the evening that is temporarily relieved by limb movement or getting up and moving around. This leads to a lack of sleep resulting in excessive daytime sleepiness, decreased work productivity, decreased quality of life and an increased risk of heart disease and stroke. Many continue to suffer despite standard of care medication use, often due to inadequate symptom control or intolerable, dose-limiting side effects of these neuroactive medications. These treatment resistant patients are left with few options for relief. Some will pursue long-term opioid treatment despite the stigma, regulatory difficulty, and potentially life-threatening side-effects. Investigation of alternative, non-medication, non-opoid options is crucially needed. Neuromodulation via spinal cord stimulation (SCS) was first reported as a successful therapeutic alternative for RLS in a patient with neuropathic pain by the primary investigator in 2016. Since then, there has been a growing number of reports corroborating this observation. However, these reports are limited to patients (with exception of one) with neuropathic pain and co-morbid RLS. To address this knowledge gap, rigorous study of SCS as a potential safe and effective novel therapy for treatment resistant, primary RLS is needed. Here we will utilize the collaborative expertise at UAB, international experts in RLS at John Hopkins and national experts in SCS at UCSF, along with our industry partner Saluda Medical (pioneer in adaptive/closed loop SCS) to perform a first-in-human controlled assessment of safety, patient acceptance, and preliminary effectiveness of SCS for primary, treatment resistant RLS. We will measure patient subjective, clinician subjective, and objective outcomes to assess for safety and improvement in RLS symptoms, sleep, and quality of life. Additionally, will use a combination of standard laboratory and novel home ambulatory measurements of sleep and leg movements. Furthermore, we will use a multimodal neurophysiology approach to test the spinal cord hypersensitivity pathophysiology theory of RLS. Our vision is to use this proven safe and effective neuromodulatory technique for neuropathic pain towards this novel indication to reduce human suffering while furthering our understanding of RLS pathophysiology and SCS mechanisms. Project Number: 1UG3NS145980-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Neurological Disorders and Stroke (NINDS) | Principal Investigator: Marshall Holland (+1 co-PI) | Institution: UNIVERSITY OF ALABAMA AT BIRMINGHAM, BIRMINGHAM, AL | Award Amount: $644,394 | Activity Code: UG3 | Study Section: Special Emphasis Panel[ZRG1 NV-J (53)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11266425