Neuromodulation to Overcome Severe Restless Legs Syndrome (NO RLS)

Neuromodulation to Overcome Severe Restless Legs Syndrome (NO RLS)

This prospective, single-center, first-in-indication feasibility study will evaluate the safety and preliminary effectiveness of spinal cord stimulation (SCS) for the treatment of severe, treatment-refractory primary Restless Legs Syndrome (RLS). Participants will undergo implantation of the Saluda Medical Evoke® Spinal Cord Stimulation System and will be followed for 24 months with clinical, neurophysiological, and patient-reported outcome assessments.

Study Overview

• Status: Not yet recruiting
• Conditions: Restless Leg Syndrome (RLS); Spinal Cord Stimulation (SCS)
• Intervention / Treatment: Device: Spinal Cord Stimulation

Detailed Description

Restless Legs Syndrome (RLS) is a chronic neurological disorder characterized by an urge to move the legs that disrupts sleep and quality of life. Current medical therapies often lose effectiveness over time or are associated with significant side effects. Preliminary case reports suggest that spinal cord stimulation (SCS) may improve RLS symptoms.

This single-arm feasibility study will enroll up to 15 adults with severe, treatment-refractory primary RLS. Participants will undergo baseline clinical, neuropsychological, and electrophysiological assessments followed by implantation of the Saluda Medical Evoke® Spinal Cord Stimulation System. Follow-up evaluations will occur through 24 months post-activation. Primary outcomes focus on device and procedure safety. Secondary outcomes evaluate changes in RLS severity, patient-reported outcomes, neurophysiological biomarkers, and device utilization.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chris Gonzalez; Phone Number: 2059964318; Email: clgonzalez@uabmc.edu

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • UAB Hospital
      • Contact: Chris Gonzalez; Phone Number: 2059964318; Email: clgonzalez@uabmc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age >18 years and older.
2. Received a medical diagnosis of RLS via first screening with Cambridge Hopkins- RLS questionnaire and confirmed via Hopkins-Hening Diagnostic questionnaire.
3. IRLS Scale score ≥ 21 (classified as severe) and received a determination of treatment refractory RLS or inadequate response to standard medical treatment for RLS by a sleep medicine physician.
4. RLS symptoms occur ≥ 3 nights per week.
5. Willing and able to comply with study procedures.
6. Able to provide informed consent.

Exclusion Criteria:

1. Age <18 years.
2. Neuropathic pain, other than RLS on DN4 questionnaire.
3. Any mental or physical limitation that would prevent completing and of the study protocols.
4. Active medical implant in the body (i.e., pacemaker).
5. History of prior SCS trial or implantation.
6. Currently using another device to treat RLS.
7. Unable or unwilling to comply with study protocols.
8. Other medical conditions that would put the subject at risk as determined by the investigators.
9. Pregnant, breastfeeding, or trying to become pregnant.
10. Currently participating or plans to participate in any other investigational clinical evaluation during the study period that may, in the opinion of the investigators, affect RLS.
11. Ferritin < 50 ng/mL (excludes iron deficiency).
12. HgA1C > 7.5 (excludes unstable diabetes melilitus)
13. One or more of the following diagnoses: spinal cord injury or prior spinal surgery, severe peripheral neuropathy, severe psychiatric or cognitive disorder that may interfere with study participation, history of drug or alcohol abuse within the past year, epilepsy or seizure disorder, current active or chronic infection other than common cold, malignancy within the past 5 years (not including basal cell or squamous cell skin cancer), severe movement disorder (i.e., Parkinson's disease), deep vein thrombosis, multiple sclerosis, known or suspected allergy to SCS materials.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SCS Implant	Device: Spinal Cord Stimulation; Implantation of the FDA-approved Saluda Medical Evoke® Spinal Cord Stimulation System with Smartloop® Technology. Two percutaneous epidural leads will be implanted in the thoracic spine (T7-T10 region) and programmed to provide chronic spinal cord stimulation for treatment of severe RLS symptoms.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Adverse Events	Frequency, severity, and relationship of device-, stimulation-, and procedure-related adverse events.	Baseline through 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in International Restless Legs Syndrome Scale (IRLS)	The IRLS is a validated 10-item patient-reported measure of Restless Legs Syndrome severity. Scores range from 0 to 40, with higher scores indicating worse symptom severity. A decrease in score from baseline indicates improvement.	Baseline through 24 months
Clinician Global Impression Improvement Scale (CGI-I)		Baseline through 24 months
Patient Global Impression of Improvement (PGI-I)	The PGI-I is a patient-reported global rating of change in symptoms and overall condition following treatment. Scores range from 1 to 7, where 1 = Very much improved and 7 = Very much worse. Lower scores represent a better outcome and greater perceived improvement.	Baseline through 24 months
Suggested Immobilization Test (SIT)		Baseline through 24 months
PROMIS Sleep, Pain, Anxiety, Depression, Cognition, and Health Measures		Baseline through 24 months
Changes in Neurophysiological Measures of Spinal Cord Stimulation Response	Changes in H-reflexes, somatosensory evoked potentials (SSEPs), EEG measures, and device-recorded ECAPs.	Baseline through 24 months
Patient-Reported Outcomes Measurement Information System - Sleep	Questionnaire assessing perceived sleep quality and difficulty falling asleep during the previous 7 days. Responses are converted to PROMIS standardized T-scores. Higher scores indicate greater sleep disturbance and a worse outcome. The T-score range is approximately 20 to 80	Baseline through 24 months
Patient-Reported Outcomes Measurement Information System - Pain	Questionnaire assessing the impact of pain on daily activities and sleep during the previous 7 days. Responses are converted to PROMIS standardized T-scores. Higher scores indicate greater pain interference and a worse outcome. The T-score range is approximately 30 to 80	Baseline through 24 months
Patient-Reported Outcomes Measurement Information System - Anxiety	Questionnaire assessing fear, anxious mood, and anxiety-related symptoms during the previous 7 days. Responses are converted to PROMIS standardized T-scores. Higher scores indicate greater anxiety and a worse outcome. The T-score range is approximately 40 to 85.	Baseline through 24 months
Patient-Reported Outcomes Measurement Information System - Depression	Questionnaire assessing depressive symptoms, negative mood, and diminished self-worth during the previous 7 days. Responses are converted to PROMIS standardized T-scores. Higher scores indicate greater depressive symptom burden and a worse outcome. The T-score range is approximately 40 to 85.	Baseline through 24 months
Patient-Reported Outcomes Measurement Information System - Cognition	Questionnaire assessing perceived cognitive abilities including memory, concentration, and mental acuity. Responses are converted to PROMIS standardized T-scores . Higher scores indicate better cognitive functioning and a better outcome. The T-score range is approximately 20 to 80.	Baseline through 24 months
Patient-Reported Outcomes Measurement Information System - Mental health battery	Assesses overall mental health. Responses are converted to PROMIS standardized T-scores. Higher scores indicate better overall health status and a better outcome. T-score range is approximately 20 to 80	Baseline through 24 months
Patient-Reported Outcomes Measurement Information System - Physical Health Battery	Assesses Overall Physical Health. Responses are converted to PROMIS standardized T-scores. Higher scores indicate better overall health status and a better outcome. T-score range is approximately 20 to 80	Baseline through 24 months

Collaborators and Investigators

• Sponsor: Marshall Holland
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: Marshall Holland, MD, University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): October 1, 2033
• Study Completion (Estimated): October 1, 2034

Study Registration Dates

• First Submitted: August 7, 2026
• First Submitted That Met QC Criteria: August 18, 2026
• First Posted (Actual): August 21, 2026

Study Record Updates

• Last Update Posted (Actual): August 21, 2026
• Last Update Submitted That Met QC Criteria: August 18, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: SCS; RLS
• Additional Relevant MeSH Terms: Nervous System Diseases; Mental Disorders; Sleep Wake Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Parasomnias; Restless Legs Syndrome; Therapeutics; Physical Therapy Modalities; Rehabilitation; Electric Stimulation Therapy; Spinal Cord Stimulation
• Other Study ID Numbers: IRB-300013464; 1UG3NS145980-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes