Spinal Cord Stimulation for Restless Legs Syndrome

NCT ID: NCT03539081

Last Updated: 2023-09-21

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-07-05

Study Completion Date

2020-04-23

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.

Conditions

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Restless Legs Syndrome Neuropathic Pain

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Subjects with RLS

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.

Group Type EXPERIMENTAL

Dual-energy X-ray absorptiometry Scan

Intervention Type DIAGNOSTIC_TEST

Body composition analysis will be obtained by DEXA scan.

Laboratory Measurements

Intervention Type OTHER

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

Blood Flow Measurement

Intervention Type OTHER

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.

Partial pressure of oxygen

Intervention Type OTHER

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

Microneurography

Intervention Type OTHER

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.

Anthropometric Measurements

Intervention Type OTHER

Height and weight will be obtained.

John Hopkins Restless Legs Severity Scale

Intervention Type BEHAVIORAL

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

Subjects without RLS

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.

Group Type OTHER

Dual-energy X-ray absorptiometry Scan

Intervention Type DIAGNOSTIC_TEST

Body composition analysis will be obtained by DEXA scan.

Laboratory Measurements

Intervention Type OTHER

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

Blood Flow Measurement

Intervention Type OTHER

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.

Partial pressure of oxygen

Intervention Type OTHER

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

Microneurography

Intervention Type OTHER

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.

Anthropometric Measurements

Intervention Type OTHER

Height and weight will be obtained.

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.

Subject will have received the standard of care intervention of epidural spinal cord stimulation for pain.

Group Type OTHER

Continuous Blood Pressure

Intervention Type OTHER

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.

Continuous Blood Pressure Diary

Intervention Type BEHAVIORAL

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

Interventions

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Dual-energy X-ray absorptiometry Scan

Body composition analysis will be obtained by DEXA scan.

Intervention Type DIAGNOSTIC_TEST

Laboratory Measurements

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

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type OTHER

Anthropometric Measurements

Height and weight will be obtained.

Intervention Type OTHER

John Hopkins Restless Legs Severity Scale

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

Intervention Type BEHAVIORAL

Continuous Blood Pressure Diary

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

Intervention Type BEHAVIORAL

Other Intervention Names

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DEXA 24-hour Ambulatory Blood Pressure Cuff

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Marshall Holland

OTHER

Sponsor Role lead

Responsible Party

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Marshall Holland

MD

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Marshall Holland, MD

Role: PRINCIPAL_INVESTIGATOR

University of Iowa

Locations

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University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status

Countries

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United States

References

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Ohayon MM, O'Hara R, Vitiello MV. Epidemiology of restless legs syndrome: a synthesis of the literature. Sleep Med Rev. 2012 Aug;16(4):283-95. doi: 10.1016/j.smrv.2011.05.002. Epub 2011 Jul 26.

Reference Type BACKGROUND
PMID: 21795081 (View on PubMed)

Earley CJ. Clinical practice. Restless legs syndrome. N Engl J Med. 2003 May 22;348(21):2103-9. doi: 10.1056/NEJMcp021288. No abstract available.

Reference Type BACKGROUND
PMID: 12761367 (View on PubMed)

Garcia-Borreguero D, Kohnen R, Boothby L, Tzonova D, Larrosa O, Dunkl E. Validation of the Multiple Suggested Immobilization Test: A Test for the Assessment of Severity of Restless Legs Syndrome (Willis-Ekbom Disease). Sleep. 2013 Jul 1;36(7):1101-1109. doi: 10.5665/sleep.2820.

Reference Type BACKGROUND
PMID: 23814348 (View on PubMed)

Cameron T. Safety and efficacy of spinal cord stimulation for the treatment of chronic pain: a 20-year literature review. J Neurosurg. 2004 Mar;100(3 Suppl Spine):254-67. doi: 10.3171/spi.2004.100.3.0254.

Reference Type BACKGROUND
PMID: 15029914 (View on PubMed)

Foreman RD, Linderoth B. Neural mechanisms of spinal cord stimulation. Int Rev Neurobiol. 2012;107:87-119. doi: 10.1016/B978-0-12-404706-8.00006-1.

Reference Type BACKGROUND
PMID: 23206679 (View on PubMed)

Yeh P, Walters AS, Tsuang JW. Restless legs syndrome: a comprehensive overview on its epidemiology, risk factors, and treatment. Sleep Breath. 2012 Dec;16(4):987-1007. doi: 10.1007/s11325-011-0606-x. Epub 2011 Oct 26.

Reference Type BACKGROUND
PMID: 22038683 (View on PubMed)

Dauvilliers Y, Winkelmann J. Restless legs syndrome: update on pathogenesis. Curr Opin Pulm Med. 2013 Nov;19(6):594-600. doi: 10.1097/MCP.0b013e328365ab07.

Reference Type BACKGROUND
PMID: 24048084 (View on PubMed)

Garcia-Borreguero D, Kohnen R, Silber MH, Winkelman JW, Earley CJ, Hogl B, Manconi M, Montplaisir J, Inoue Y, Allen RP. The long-term treatment of restless legs syndrome/Willis-Ekbom disease: evidence-based guidelines and clinical consensus best practice guidance: a report from the International Restless Legs Syndrome Study Group. Sleep Med. 2013 Jul;14(7):675-84. doi: 10.1016/j.sleep.2013.05.016.

Reference Type BACKGROUND
PMID: 23859128 (View on PubMed)

Hornyak M, Scholz H, Kohnen R, Bengel J, Kassubek J, Trenkwalder C. What treatment works best for restless legs syndrome? Meta-analyses of dopaminergic and non-dopaminergic medications. Sleep Med Rev. 2014 Apr;18(2):153-64. doi: 10.1016/j.smrv.2013.03.004. Epub 2013 Jun 6.

Reference Type BACKGROUND
PMID: 23746768 (View on PubMed)

Walters AS, Wagner ML, Hening WA, Grasing K, Mills R, Chokroverty S, Kavey N. Successful treatment of the idiopathic restless legs syndrome in a randomized double-blind trial of oxycodone versus placebo. Sleep. 1993 Jun;16(4):327-32. doi: 10.1093/sleep/16.4.327.

Reference Type BACKGROUND
PMID: 8341893 (View on PubMed)

Goldberg LI. Dopamine receptors and hypertension. Physiologic and pharmacologic implications. Am J Med. 1984 Oct 5;77(4A):37-44. doi: 10.1016/s0002-9343(84)80036-4.

Reference Type BACKGROUND
PMID: 6148892 (View on PubMed)

Wu M, Linderoth B, Foreman RD. Putative mechanisms behind effects of spinal cord stimulation on vascular diseases: a review of experimental studies. Auton Neurosci. 2008 Feb 29;138(1-2):9-23. doi: 10.1016/j.autneu.2007.11.001.

Reference Type BACKGROUND
PMID: 18083639 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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201605777

Identifier Type: -

Identifier Source: org_study_id

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