Spinal Cord Stimulation for Restless Legs Syndrome

Study Overview
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Brief Summary
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The overall goal of this proposed study is to evaluate the underlying mechanisms of neural control of blood flow in the lower extremities in humans with restless leg syndrome (RLS). At least 15% of the general public suffers from RLS and many more may go undiagnosed. This unfortunate disorder leads primarily to a disturbing sensation within the patient's lower extremities that requires movement for relief (1, 2). The central hypothesis of our study is that physiological changes in lower limb blood flow as a result of thoracolumbar epidural Spinal Cord Stimulation (SCS) lead to the relief of RLS.

Detailed Description
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Patients age 18-85 years with (n=25) and without RLS (n=25) that have recently having undergone Spinal Cord Stimulation (SCS) implantation (thoracolumbar) for chronic pain will be recruited from the Departments of Anesthesia and Neurosurgery, University of Iowa Hospitals and Clinics. The rationale for studying both RLS patients and non-RLS patients with chronic back pain is to initially test the effectiveness of Spinal Cord Stimulation (SCS) on lower limb blood flow in the absence of symptoms of RLS. In the non-RLS patients, we could determine if SCS does in fact alter limb blood flow. We hypothesize that RLS patients have altered muscle sympathetic nerve activity (MSNA) and blood flow correlating to severity of RLS symptoms, which will then be modulated by Spinal Cord Stimulation (SCS), allowing for resolution of symptoms in RLS with MSNA-mediated improvements in leg blood flow. We also hypothesize that SCS in RLS patients will reduce 24-hour ambulatory blood pressure in parallel with reductions in MSNA. Those deemed eligible to participate will be invited for 2 visits to the Translational Vascular Physiology Laboratory in the Clinical Research Unit (CRU) of the University of Iowa Hospitals and Clinics. Each of the 2 study visits are identical except for experimental measurements that are made at each of the five measurement time points when the Spinal Cord Stimulation (SCS) unit is either on or off as described below. Visit 1: Experimental measurements include non-invasive gold standard measures of limb blood flow and arterial stiffness including femoral artery blood flow via Doppler ultrasound, calf blood flow from strain gauge venous occlusion plethysmography, and arterial stiffness via pulse wave velocity using applanation tonometry. Additionally, participants will be asked to assess the current level of leg discomfort every 10 minutes while measurements are taken by the SIT test, a validated technique for assessing restless legs symptoms where patients are asked to set and rest quietly during measurement talking, moving as little as possible (3). Visit 2: Experimental measurements include direct measures of sympathetic nerve activity using microneurography before, during and again after administration of SCS to the patient. Additionally, participants will be asked to assess the current level of leg discomfort every 10 minutes while measurements are taken by the SIT test, a validated technique for assessing restless legs symptoms where patients are asked to set and rest quietly during measurement taking, moving as little as possible (3). Some participates may visit the laboratory for placement of a 24-hour ambulatory blood pressure cuff.

Official Title
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Investigating Mechanisms of Human Spinal Cord Stimulation for Purpose of Treating Restless Leg Syndrome

Conditions
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Restless Legs Syndrome, Neuropathic Pain

Intervention / Treatment
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* Diagnostic Test: Dual-energy X-ray absorptiometry Scan
* Other: Laboratory Measurements
* Other: Blood Flow Measurement
* Other: Continuous Blood Pressure
* Other: Partial pressure of oxygen
* Other: Microneurography
* Other: Anthropometric Measurements
* Behavioral: John Hopkins Restless Legs Severity Scale
* Behavioral: Continuous Blood Pressure Diary


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Mental capacity to understand and decide to participate in the research Recently have undergone or are planning to undergo SCS implantation (thoracolumbar region) for chronic pain. Exclusion Criteria: Peripheral vascular disease History of ischemic heart disease ( examples myocardial infarction, cardiac bypass surgery, coronary stent, unstable angina) Heart transplantation Renal Failure Congestive heart failure Type 1 diabetes Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects are assigned to one of two groups based on whether they have Restless Leg Syndrome to undergo experimental measurements that are made at each of the five measurement time points.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Subjects with RLS<br>Subjects with Restless Leg Syndrome that have recently undergone Spinal Cord Stimulation (SCS) Implantation for chronic pain. Subject will have received the standard of care intervention of epidural spinal cord stimulation for pain. | Diagnostic Test: Dual-energy X-ray absorptiometry Scan<br>* Body composition analysis will be obtained by DEXA scan.<br>* Other names: DEXA;Other: Laboratory Measurements<br>* The following labs will be obtained during the course of the study: pregnancy test (urine), glucose, insulin, catecholamine, and cholesterol (serum).<br>Other: Blood Flow Measurement<br>* The blood flow to the arm or leg may also be measured by placing an ultrasonic probe on the skin over the femoral artery of the leg and the brachial artery of the arm.<br>Other: Partial pressure of oxygen<br>* Transcutaneous recordings will be captured to measure the partial pressure of oxygen by placing monitors on the subject's chest and foot.<br>Other: Microneurography<br>* The sympathetic nervous system activity to the subject's leg muscles will be measured by a tiny microelectrode placed in the peroneal nerve in the leg located just below the knee on the outer part of the leg. When the nerve is located 2 tiny sterile microelectrodes will be inserted through the skin.<br>Other: Anthropometric Measurements<br>* Height and weight will be obtained.<br>Behavioral: John Hopkins Restless Legs Severity Scale<br>* Subjects will be administered questionnaires to evaluate RLS symptoms using John Hopkins Restless Legs Severity Scale.<br>|
| Other: Subjects without RLS<br>Subjects without Restless Leg Syndrome that have recently undergone Spinal Cord Stimulation (SCS) Implantation for chronic pain. Subject will have received the standard of care intervention of epidural spinal cord stimulation for pain. | Diagnostic Test: Dual-energy X-ray absorptiometry Scan<br>* Body composition analysis will be obtained by DEXA scan.<br>* Other names: DEXA;Other: Laboratory Measurements<br>* The following labs will be obtained during the course of the study: pregnancy test (urine), glucose, insulin, catecholamine, and cholesterol (serum).<br>Other: Blood Flow Measurement<br>* The blood flow to the arm or leg may also be measured by placing an ultrasonic probe on the skin over the femoral artery of the leg and the brachial artery of the arm.<br>Other: Partial pressure of oxygen<br>* Transcutaneous recordings will be captured to measure the partial pressure of oxygen by placing monitors on the subject's chest and foot.<br>Other: Microneurography<br>* The sympathetic nervous system activity to the subject's leg muscles will be measured by a tiny microelectrode placed in the peroneal nerve in the leg located just below the knee on the outer part of the leg. When the nerve is located 2 tiny sterile microelectrodes will be inserted through the skin.<br>Other: Anthropometric Measurements<br>* Height and weight will be obtained.<br>|
| Other: Continous BP Monitoring<br>This arm consists of subjects from arm Subjects with RLS, Subjects without RLS, and the rest of the qualifying subjects undergoing continuous blood pressure portion of the study only. Subject will have received the standard of care intervention of epidural spinal cord stimulation for pain. | Other: Continuous Blood Pressure<br>* Continuous Blood pressure cuff will worn for 2 days with spinal cord stimulator on and off (24 hour on and 24 hour off). Optional procedure.<br>* Other names: 24-hour Ambulatory Blood Pressure Cuff;Behavioral: Continuous Blood Pressure Diary<br>* Subjects participating in Continuous Blood Pressure monitoring will be administered continuous blood pressure monitoring compliance diary.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change MSNA Burst Frequency From Baseline to 60 Minutes | Response will measured by peroneal nerve microneurography to the lower limb during epidural spinal cord stimulation in patients with chronic back pain. Percent change MSNA burst frequency from baseline to 60 minutes | Baseline to 60 minutes | 
| Response Measurement of Thoracolumbar Epidural SCS in the Femoral Artery Blood Flow | The response will be measured by Doppler ultrasound of the femoral artery during epidural spinal cord stimulation in patients with chronic back pain. | Baseline and 1.5 Hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epidural Spinal Cord Stimulation, Muscle Sympathetic Nerve Activity, Blood Flow