Transcutaneous Spinal Cord Neuromodulation to Normalize Autonomic Phenotypes

Study Overview
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Brief Summary
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This study looks to characterize autonomic nervous system dysfunction after spinal cord injury and identify the potential role that transcutaneous spinal cord stimulation may play at altering neuroregulation. The autonomic nervous system plays key parts in regulation of blood pressure, skin blood flow, and bladder health- all issues that individuals with spinal cord injury typically encounter complications. For both individuals with spinal cord injury and uninjured controls, experiments will utilize multiple parallel recordings to identify how the autonomic nervous system is able to inhibit and activate sympathetic signals. The investigators anticipate that those with autonomic dysfunction after spinal cord injury will exhibit abnormalities in these precise metrics. In both study populations, transcutaneous spinal cord stimulation will be added, testing previously advocated parameters to alter autonomic neuroregulation. In accomplishing this, the investigators hope to give important insights to how the autonomic nervous system works after spinal cord injury and if it's function can be improved utilizing neuromodulation.

Official Title
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Transcutaneous Spinal Neuromodulation to Normalize Autonomic Phenotypes

Conditions
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Spinal Cord Injuries, Autonomic Imbalance, Autonomic Dysreflexia, Orthostatic; Hypotension, Neurogenic

Intervention / Treatment
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* Diagnostic Test: Tests of sympathetic inhibition
* Diagnostic Test: Tests of sympathetic activation
* Diagnostic Test: Testing of autonomic dysreflexia
* Device: Transcutaneous spinal cord stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All participants - age 18-30 years old. Participants with spinal cord injury Adult onset, traumatic spinal cord injury. Time since injury 1 year, in an effort to limit baroreflex desensitization. American Spinal Injury Association Impairment Scale, A, to limit potential confounders. Neurological level of injury, T1-T6, as defined by the International Standards for Neurological Classification of Spinal Cord Injury. Exclusion Criteria: History of cardiovascular disease, hypertension, neurologic disorders (with exception of spinal cord injury), or diabetes. Women who are pregnant or lactating. Currently taking blood thinners. Taking anti-hypertensive or other medication that could influence any of the dependent autonomic variables.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Individuals with spinal cord injury<br> | Diagnostic Test: Tests of sympathetic inhibition<br>* Bolus phenylephrine infusion using the Oxford technique will generate the need to inhibit sympathetic activity. Similarly, resting state Mayer waves will be assessed with regard to heart rate and blood pressure responses.<br>Diagnostic Test: Tests of sympathetic activation<br>* Cold pressor test of the hand will be used to cause sympathetic activation. Valsalva's maneuver will assess the ability to buffer against blood pressure fall (phase II).<br>Diagnostic Test: Testing of autonomic dysreflexia<br>* Cold pressor test of the foot and bladder pressor response (in individuals with SCI) will be tested.<br>Device: Transcutaneous spinal cord stimulation<br>* Transcutaneous spinal cord stimulation will be applied at T7-L1 spinal segments to assess alterations in autonomic neuroregulation.<br>|
| Experimental: Individuals without spinal cord injury<br> | Diagnostic Test: Tests of sympathetic inhibition<br>* Bolus phenylephrine infusion using the Oxford technique will generate the need to inhibit sympathetic activity. Similarly, resting state Mayer waves will be assessed with regard to heart rate and blood pressure responses.<br>Diagnostic Test: Tests of sympathetic activation<br>* Cold pressor test of the hand will be used to cause sympathetic activation. Valsalva's maneuver will assess the ability to buffer against blood pressure fall (phase II).<br>Device: Transcutaneous spinal cord stimulation<br>* Transcutaneous spinal cord stimulation will be applied at T7-L1 spinal segments to assess alterations in autonomic neuroregulation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Valsalva Maneuver Phase II | Presence or absence of phase II on Valsalva maneuver testing, which takes approximately 15 seconds to complete. This will be repeated x3. | Through study completion, average 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle sympathetic nerve activity | Microneurography will be performed to characterize cardiovascular autonomic phenotypes between uninjured controls and individuals with spinal cord injury. This will be quantified by spike frequency. | Through study completion, average 3 months | 
| Beat-to-beat heart rate | Electrocardiogram will record continuous measures with changes in R-R interval (ms) quantified and compared to baseline. | Through study completion, average 3 months | 
| Beat-to-beat blood pressure | Non-invasive continuous blood pressure monitors will be used, with changes in systolic and diastolic pressure (in mmHg) from resting baseline measured. | Through study completion, average 3 months | 
| Continuous galvanic skin response | Changes from resting state conductance with be quantified with a smartwatch. | Through study completion, average 3 months | 
| Quantify autonomic dysreflexia and orthostatic hypotension | Participants will be given the Autonomic Dysfunction Following Spinal Cord Injury questionnaire (score range 0-436, with higher scores indicating more autonomic dysfunction). | Baseline, prior to initial laboratory diagnostic testing session | 
| Quantify secondary autonomic complications | Participants will be given the Composite Autonomic Symptom Score (range 0-100, with higher scores indicating more autonomic dysfunction). | Baseline, prior to initial laboratory diagnostic testing session |