Deciphering Preserved Autonomic Function After Spinal Cord Injury

Study Overview
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Brief Summary
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This study looks to characterize gradients of dysfunction in the autonomic nervous system after spinal cord injury. The autonomic nervous system plays key roles in regulation of blood pressure, skin blood flow, and bladder health- all issues that individuals with spinal cord injury typically suffer. Focusing on blood pressure regulation, the most precise metric with broad clinical applicability, the investigators will perform a combination of laboratory, ambulatory, and imaging-based tests to probe the body's ability to generate autonomic responses. For both individuals with spinal cord injury and uninjured controls, laboratory-based experiments will utilize multiple parallel recordings to identify how the autonomic nervous system is able to inhibit and activate signals. The investigators anticipate that those with autonomic dysfunction after spinal cord injury will exhibit abnormalities in these precise metrics. The investigators will further have research participants wear a smart watch that tracks skin electrical conductance, heart rate, and skin temperature, which can all provide clues as to the degree of autonomic dysfunction someone may suffer at home. The investigators will look to see if any substantial connections exist between different degrees of preserved autonomic function and secondary autonomic complications from spinal cord injury. Finally, functional magnetic resonance imaging scans will be attained to characterize patterns of connectivity within the injured spinal cord. In a similar manner, the investigators will look to see if different patterns of spinal cord connectivity are more closely related to groupings of secondary autonomic complications. In accomplishing this, the investigators hope to give scientists important insights to how the autonomic nervous system works after spinal cord injury and give physicians better tools to manage these secondary autonomic complications.

Detailed Description
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This study looks to characterize gradients of dysfunction in the autonomic nervous system after spinal cord injury. To accomplish this, we are enrolling both individuals with and without spinal cord injuries (see inclusion criteria). Individuals will undergo the listed diagnostics as part of a battery of laboratory testing. These will be correlated to clinical histories of autonomic dysfunction the ADFSCI and COMPASS-31 surveys (noted in outcome measures). Imaging-based tests will further probe the body's ability to generate autonomic responses.

Official Title
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Deciphering Preserved Autonomic Function After Spinal Cord Injury

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

Intervention / Treatment
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* Diagnostic Test: Tests of sympathetic inhibition
* Diagnostic Test: Tests of sympathetic activation
* Diagnostic Test: Testing of autonomic dysreflexia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All subjects - age 18-50 years old. Participants with spinal cord injury Adult onset, traumatic spinal cord injury. Time since injury restricted to 1-5 years, in an effort to limit baroreflex desensitization. American Spinal Injury Association Impairment Scale, A-D, to encompass a spectrum of autonomic dysfunction after spinal cord injury. Neurological level of injury, C1-T12, as defined by the International Standards for Neurological Classification of Spinal Cord Injury. Incorporating level of injury down to T12 to encompass a broad range of autonomic dysfunction. 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. Pacemaker, implanted defibrillator, or intrathecal pump incompatible with MRI scanning. Cognitive issues preventing informed consent for participation. Body mass index >30 kg/m2 for controls, in an effort to limit effects of early cardiovascular disease and diabetes in control population. Body mass index has not proven to be a good estimate of these factors following spinal cord injury.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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>|
| 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>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>|

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. | During laboratory diagnostic testing session | 

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. | During laboratory diagnostic testing session | 
| Beat-to-beat heart rate | Electrocardiogram will record continuous measures with changes in R-R interval (ms) quantified and compared to baseline. | During laboratory diagnostic testing session | 
| 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. | During laboratory diagnostic testing session | 
| Continuous galvanic skin response | Changes from resting state conductance with be quantified with a smartwatch. | During laboratory diagnostic testing session | 
| Continuous wrist temperature | Changes from resting state temperature with be quantified with a smartwatch. | During laboratory diagnostic testing session | 
| 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 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 laboratory diagnostic testing session | 
| Identify amplified functional connectivity within the spinal cord | High-field spinal cord functional magnetic resonance imaging will be attained for all individuals to determine relative activation of spinal networks at rest and during mild noxious stimulus. | During diagnostic imaging session |