Spinal Cord Stimulation for Restless Legs Syndrome

Neuropathic Pain Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03539081
• Other study ID #: 201605777
• Status: Completed
• Phase: N/A
• Start date: July 5, 2016
• Est. completion date: April 23, 2020

Study information

• Verified date: August 2023
• Source: University of Iowa
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: April 23, 2020
• Est. primary completion date: April 23, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Neuralgia
• Neuropathic Pain
• Psychomotor Agitation
• Restless Legs Syndrome
• Syndrome

Intervention

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

Other:
• Laboratory Measurements
The following labs will be obtained during the course of the study: pregnancy test (urine), glucose, insulin, catecholamine, and cholesterol (serum).
• 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.
• 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.
• 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.
• 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.
• 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.
• Continuous Blood Pressure Diary
Subjects participating in Continuous Blood Pressure monitoring will be administered continuous blood pressure monitoring compliance diary.

Locations

Country	Name	City	State
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa

Sponsors (1)

Lead Sponsor	Collaborator
Marshall Holland

Country where clinical trial is conducted

United States, 

References & Publications (12)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Erratum In: Sleep Med Rev. 2014 Aug;18(4):367-8. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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