Spinal Cord Stimulation for Restless Legs Syndrome

NCT03539081 | Completed Results FDA Device

• 1 other identifier: 201605777
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Restless Legs Syndrome; Neuropathic Pain

Keywords

Epidural Spinal Cord Stimulation; Muscle Sympathetic Nerve Activity; Blood Flow

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (3)

Subjects with RLS

EXPERIMENTAL

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; Other: Laboratory Measurements; Other: Blood Flow Measurement; Other: Partial pressure of oxygen; Other: Microneurography; Other: Anthropometric Measurements; Behavioral: John Hopkins Restless Legs Severity Scale

Subjects without RLS

OTHER

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; Other: Laboratory Measurements; Other: Blood Flow Measurement; Other: Partial pressure of oxygen; Other: Microneurography; Other: Anthropometric Measurements

Continous BP Monitoring

OTHER

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; Behavioral: Continuous Blood Pressure Diary

Interventions

Dual-energy X-ray absorptiometry Scan DIAGNOSTIC_TEST

Body composition analysis will be obtained by DEXA scan.

Also known as: DEXA

Subjects with RLS; Subjects without RLS

Laboratory Measurements OTHER

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

Subjects with RLS; Subjects without RLS

Blood Flow Measurement 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.

Subjects with RLS; Subjects without RLS

Continuous Blood Pressure 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.

Also known as: 24-hour Ambulatory Blood Pressure Cuff

Continous BP Monitoring

Partial pressure of oxygen OTHER

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

Subjects with RLS; Subjects without RLS

Microneurography 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.

Subjects with RLS; Subjects without RLS

Anthropometric Measurements OTHER

Height and weight will be obtained.

Subjects with RLS; Subjects without RLS

John Hopkins Restless Legs Severity Scale BEHAVIORAL

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

Subjects with RLS

Continuous Blood Pressure Diary BEHAVIORAL

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

Continous BP Monitoring

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Marshall Holland: lead

Study Sites (1)

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Related Publications (12)

• 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.

  PMID: 21795081 BACKGROUND

• 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.

  PMID: 12761367 BACKGROUND

• 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.

  PMID: 23814348 BACKGROUND

• 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.

  PMID: 15029914 BACKGROUND

• 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.

  PMID: 23206679 BACKGROUND

• 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.

  PMID: 22038683 BACKGROUND

• 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.

  PMID: 24048084 BACKGROUND

• 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.

  PMID: 23859128 BACKGROUND

• 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.

  PMID: 23746768 BACKGROUND

• 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.

  PMID: 8341893 BACKGROUND

• 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.

  PMID: 6148892 BACKGROUND

• 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.

  PMID: 18083639 BACKGROUND

MeSH Terms

Conditions

Restless Legs Syndrome; Neuralgia

Interventions

Absorptiometry, Photon; Blood Pressure Monitors; PO-2

Condition Hierarchy (Ancestors)

Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Parasomnias; Mental Disorders; Peripheral Nervous System Diseases; Neuromuscular Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Radiography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Densitometry; Photometry; Chemistry Techniques, Analytical; Investigative Techniques; Sphygmomanometers; Diagnostic Equipment; Equipment and Supplies

Results Point of Contact

• Title: Marshall Holland, MD
• Organization: University of Iowa

mtholland@uabmc.edu

205-934-2654

Study Officials

• Marshall Holland, MD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Model Details: 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.

Study Record Dates

• First Submitted: May 15, 2018
• First Posted: May 29, 2018
• Study Start: July 5, 2016
• Primary Completion: April 23, 2020
• Study Completion: April 23, 2020
• Last Updated: September 21, 2023
• Results First Posted: September 21, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)