Deciphering Preserved Autonomic Function After Spinal Cord Injury

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 laboratory-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. 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.

Study Overview

• Status: Suspended
• Conditions: Spinal Cord Injuries; Orthostatic Hypotension; Autonomic Dysreflexia; Autonomic Imbalance
• Intervention / Treatment: Diagnostic test: Tests of sympathetic inhibition; Diagnostic test: Tests of sympathetic activation; Diagnostic test: Testing of autonomic dysreflexia

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Estimated): 69
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55902
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

All subjects

- age 18-50 years old.

Participants with spinal cord injury

• Adult onset, traumatic spinal cord injury.
• 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Individuals with spinal cord injury	Diagnostic test: Tests of sympathetic inhibition; 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.; Diagnostic test: Tests of sympathetic activation; 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).; Diagnostic test: Testing of autonomic dysreflexia; Cold pressor test of the foot and bladder pressor response (in individuals with SCI) will be tested.
Experimental: Individuals without spinal cord injury	Diagnostic test: Tests of sympathetic inhibition; 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.; Diagnostic test: Tests of sympathetic activation; 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).; Diagnostic test: Testing of autonomic dysreflexia; Cold pressor test of the foot and bladder pressor response (in individuals with SCI) will be tested.

What is the study measuring?

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
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

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Ryan Solinsky, MD, Mayo Clinic

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2020
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: July 17, 2020
• First Submitted That Met QC Criteria: July 28, 2020
• First Posted (Actual): July 30, 2020

Study Record Updates

• Last Update Posted (Estimated): February 13, 2024
• Last Update Submitted That Met QC Criteria: February 9, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Spinal Cord Diseases; Autonomic Nervous System Diseases; Primary Dysautonomias; Orthostatic Intolerance; Wounds and Injuries; Hypotension; Spinal Cord Injuries; Hypotension, Orthostatic; Autonomic Dysreflexia
• Other Study ID Numbers: 23-005772

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No