Transcutaneous Stimulation in Spinal Cord Injury

Study Overview
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Brief Summary
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Cardiovascular disease has become the leading cause of death in the spinal cord injury population. Increased reliance on the renin-angiotensin-aldosterone system (RAAS) is believed to decrease falls in blood pressure when moving from a laying down position to upright; however, findings in the general population link the RAAS with remodeling and restructuring of the arterial walls. Therefore, intervention to stabilize and normalize blood pressure should be a priority in individuals with spinal cord injury who have low blood pressure. Advances in stimulation on the skin of the spinal cord offer an approach to restore cardiovascular control and improve blood pressure regulation; however, electrode placement and stimulation parameters needed to increase blood pressure are not well understood. Therefore, the aim of the study is to identify placement of electrodes on the skin, and frequency and amplitude of the stimulation to regulate blood pressure.

Detailed Description
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Although life expectancies have improved in the SCI population, longevity remains below the general population, due to increased incidence of cardiovascular disease, which is the leading cause of mortality in individuals with chronic SCI. Autonomic nervous system dysfunction and blood pressure instability contribute to the increased cardiovascular disease risk in the SCI population; however, because a majority of individuals with SCI remain asymptomatic the diagnosis and treatment of blood pressure instability is not a clinical priority. This is due, in part, to lack of safe and effective interventions, even though mounting evidence strongly supports adverse effects of blood pressure instability on the cerebral circulation, cognitive function, and quality of life. Identifying individualized transcutaneous stimulation parameters that safely and effectively increase and stabilize blood pressure in hypotensive individuals with SCI will provide the foundational evidence to support eventual wide-spread clinical utility throughout the VA healthcare system. 10 participants who are cleared, will go through multiple mapping sessions to find out the most appropriate electrode placement to increase blood pressure and then will perform an orthostatic provocation on a tilt table during stimulation to determine differences with stim and without. The study will take approximately 1 to 13 study visits, of between 3-5 hours, per participant.

Official Title
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Targeted Transcutaneous Stimulation to Restore Autonomic Cardiovascular Health in Veterans With Spinal Cord Injury

Conditions
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Spinal Cord Injury

Intervention / Treatment
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* Device: DS8R
* Diagnostic Test: Orthostatic tilt


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: above the age of 18 years old individuals with traumatic spinal cord injuries at or above T6 duration of injury if more than 1 year non-ambulatory American spinal injury association scale A, B or C able to provide consent non-ventilator hypotensive (males: systolic blood pressure less than 110 mmHg and/or diastolic blood pressure less than 70 mmHg; females: systolic blood pressure less than 100 mmHg and/or diastolic blood pressure less than 70 mmHg) Exclusion Criteria: acute illness or infection documented history of controlled or uncontrolled diabetes any other neurological disease other than spinal cord injury cardiovascular disease (coronary artery disease, congestive heart failure, peripheral artery disease, stroke) present of history of thrombosis in the last 12 months, severe contractures pregnant

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: All participants will complete transcutanous stimulation mapping sessions to determine the optimal parameters to increase and maintain systolic blood pressure between 110-120 mmHg for males and 100-120 mmHg for females. The last two (or three) visits, the participants will be blinded to the order of completing an orthostatic tilt with and without stimulation. The third visit might be needed if the amplitude of the intensity that was found to be optimal in the seated position needs to be increased during a tilt to increase systolic blood pressure.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Without Stimulation<br>Participant will complete an orthostatic challenge without transcutaneous stimulation. | Diagnostic Test: Orthostatic tilt<br>* perform an orthostatic tilt without and with stimulation.<br>|
| Active Comparator: With Stimulation<br>Participant will complete an orthostatic challenge with transcutaneous stimulation. | Device: DS8R<br>* transcutaneous stimulation of the spinal cord.<br>* Other names: Transcutaneous Stimulation;Diagnostic Test: Orthostatic tilt<br>* perform an orthostatic tilt without and with stimulation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Electrode placement | Electrodes will be placed on the vertebral midline at the spinous process (T7/T8, T9/10, T11/12, L1/L2). Determine the best electrode placement on the spine that increases blood pressure between 110-120 mmHg for males and 100-120 mmHg for females in the seated position. The best electrode placement will be used to increase blood pressure during an orthostatic tilt. | through study completion, up to 2 years | 
| Amplitude of TSCS | Amplitude of the stimulation will start at 0mA and increase in increments between 1 - 10mA to determine the best amplitude to increase systolic blood pressure between 110-120 mmHg for males and 100-120 mmHg for females. The same spinous process sites (T7/T8, T9/10, T11/12, L1/L2) will be used. The best amplitude will be used to increase blood pressure during an orthostatic tilt. | through study completion, up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systolic blood pressure | Determine the differences in systolic blood pressure during an orthostatic tilt without stimulation and with optimal stimulation. | through study completion, up to 2 years | 
| Concentration of Norepinephrine | Determine the differences in norepinephrine during an orthostatic tilt without stimulation and with optimal stimulation. | through study completion, up to 2 years | 
| Velocity of Arterial stiffness | Determine the differences in arterial stiffness during an orthostatic tilt without stimulation and with optimal stimulation. Arterial stiffness will be measured using pulse wave velocity of the carotid and femoral arteries. The unit of measure is velocity. | through study completion, up to 2 years | 
| Concentration of Renin | Determine the differences in renin during an orthostatic tilt without stimulation and with optimal stimulation. | through study completion, an average of 2 years | 
| Concentration of Aldosterone | Determine the differences in aldosterone during an orthostatic tilt without stimulation and with optimal stimulation. | through study completion, an average of 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Blood pressure, Orthostatic hypotension, Transcutaneous stimulation, Cardiovascular disease