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Spinal Cord Stimulation for Restless Legs Syndrome

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ClinicalTrials.gov Identifier: NCT03539081
Recruitment Status : Recruiting
First Posted : May 28, 2018
Last Update Posted : March 20, 2019
Sponsor:
Information provided by (Responsible Party):
Marshall Holland, University of Iowa

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Restless Legs Syndrome Neuropathic Pain 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 Not Applicable

Detailed Description:

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention 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)
Primary Purpose: Basic Science
Official Title: Investigating Mechanisms of Human Spinal Cord Stimulation for Purpose of Treating Restless Leg Syndrome
Actual Study Start Date : July 5, 2016
Estimated Primary Completion Date : May 1, 2020
Estimated Study Completion Date : May 1, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Restless Legs

Arm Intervention/treatment
Experimental: Subjects with RLS

Subjects with Restless Leg Syndrome that have recently undergone Spinal Cord Stimulation (SCS) Implantation for chronic pain.

Intervention: Use of epidural spinal cord stimulation.

Diagnostic Test: Dual-energy X-ray absorptiometry Scan
Body composition analysis will be obtained by DEXA scan.
Other Name: DEXA

Other: Laboratory Measurements
The following labs will be obtained during the course of the study: pregnancy test (urine), glucose, insulin, catecholamine, and cholesterol (serum).

Other: Blood Flow Measurement
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.

Other: Continuous Blood Pressure
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.
Other Name: 24-hour Ambulatory Blood Pressure Cuff

Other: Partial pressure of oxygen
Transcutaneous recordings will be captured to measure the partial pressure of oxygen by placing monitors on the subject's chest and foot.

Other: Microneurography
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.

Other: Anthropometric Measurements
Height and weight will be obtained.

Behavioral: Continuous Blood Pressure Diary
Subjects participating in Continuous Blood Pressure monitoring will be administered continuous blood pressure monitoring compliance diary.

Subjects without RLS

Subjects without Restless Leg Syndrome that have recently undergone Spinal Cord Stimulation (SCS) Implantation for chronic pain.

Intervention: Use of epidural spinal cord stimulation.

Diagnostic Test: Dual-energy X-ray absorptiometry Scan
Body composition analysis will be obtained by DEXA scan.
Other Name: DEXA

Other: Laboratory Measurements
The following labs will be obtained during the course of the study: pregnancy test (urine), glucose, insulin, catecholamine, and cholesterol (serum).

Other: Blood Flow Measurement
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.

Other: Continuous Blood Pressure
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.
Other Name: 24-hour Ambulatory Blood Pressure Cuff

Other: Partial pressure of oxygen
Transcutaneous recordings will be captured to measure the partial pressure of oxygen by placing monitors on the subject's chest and foot.

Other: Microneurography
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.

Other: Anthropometric Measurements
Height and weight will be obtained.

Behavioral: John Hopkins Restless Legs Severity Scale
Subjects will be administered questionnaires to evaluate RLS symptoms using John Hopkins Restless Legs Severity Scale.

Behavioral: Continuous Blood Pressure Diary
Subjects participating in Continuous Blood Pressure monitoring will be administered continuous blood pressure monitoring compliance diary.

Continous BP Monitoring

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.

Intervention: Use of epidural spinal cord stimulation.

Other: Continuous Blood Pressure
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.
Other Name: 24-hour Ambulatory Blood Pressure Cuff

Behavioral: Continuous Blood Pressure Diary
Subjects participating in Continuous Blood Pressure monitoring will be administered continuous blood pressure monitoring compliance diary.




Primary Outcome Measures :
  1. Thoracolumbar epidural SCS will decrease MSNA [ Time Frame: 1.5 Hours ]
    Response will measured by peroneal nerve microneurography to the lower limb during epidural spinal cord stimulation in patients with chronic back pain.

  2. Thoracolumbar epidural SCS will increase femoral artery blood flow [ Time Frame: 1.5 Hours ]
    The response will be measured by Doppler ultrasound of the femoral artery during epidural spinal cord stimulation in patients with chronic back pain.


Secondary Outcome Measures :
  1. Thoracolumbar epidural SCS will decrease MSNA in patients with RLS. [ Time Frame: 1.5 Hours ]
    Response will measured by peroneal nerve microneurography to the lower limb during epidural spinal cord stimulation.

  2. Acute thoracolumbar epidural SCS will increase femoral artery blood flow in patients with RLS. [ Time Frame: 1.5 Hours ]
    This response will be measured by Doppler ultrasound of the femoral artery.

  3. Acute thoracolumbar epidural SCS will improve severity of clinical symptoms in patients with RLS. [ Time Frame: 1.5 Hours ]
    Patients will report a subjective rating of 0-10 of current RLS symptoms during spinal cord stimulation.

  4. Acute thoracolumbar epidural SCS will improve oxygenation of the foot compared to the chest. [ Time Frame: 1.5 Hours ]
    Transcutaneous partial pressure of oxygen will be measured on patients chest and foot.


Other Outcome Measures:
  1. Thoracolumbar epidural SCS will decrease 24-hour ambulatory blood pressure. [ Time Frame: 48 hours ]
    Patients will wear continuous blood pressure monitor for 48 hours with a spinal cord simulator on and off while keeping a diary of simulator use.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03539081


Contacts
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Contact: Nataliya S Hramakova, BSN 319-384-9164 nataliya-hramakova@uiowa.edu
Contact: Marshall Holland, MD 319-356-2771 marshall-holland@uiowa.edu

Locations
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United States, Iowa
University of Iowa Hospitals and Clinics Recruiting
Iowa City, Iowa, United States, 52242
Contact: Nataliya S Hramakova, BSN    319-384-9164    nataliya-hramakova@uiowa.edu   
Contact: Marshall Holland, MD    319-356-2771    marshall-holland@uiowa.edu   
Principal Investigator: Marshall Holland, MD         
Sponsors and Collaborators
Marshall Holland
Investigators
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Principal Investigator: Marshall Holland, MD University of Iowa

Publications:

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Responsible Party: Marshall Holland, MD, University of Iowa
ClinicalTrials.gov Identifier: NCT03539081     History of Changes
Other Study ID Numbers: 201605777
First Posted: May 28, 2018    Key Record Dates
Last Update Posted: March 20, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Marshall Holland, University of Iowa:
Epidural Spinal Cord Stimulation
Muscle Sympathetic Nerve Activity
Blood Flow
Additional relevant MeSH terms:
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Neuralgia
Psychomotor Agitation
Restless Legs Syndrome
Syndrome
Disease
Pathologic Processes
Peripheral Nervous System Diseases
Neuromuscular Diseases
Nervous System Diseases
Pain
Neurologic Manifestations
Signs and Symptoms
Dyskinesias
Psychomotor Disorders
Neurobehavioral Manifestations
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Parasomnias
Mental Disorders