Transcutaneous Spinal Cord Neuromodulation to Normalize Autonomic Phenotypes

Transcutaneous Spinal Neuromodulation to Normalize Autonomic Phenotypes

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.

Study Overview

• Status: Completed
• Conditions: Spinal Cord Injuries; Autonomic Dysreflexia; Autonomic Imbalance; Orthostatic; Hypotension, Neurogenic
• Intervention / Treatment: Diagnostic test: Tests of sympathetic inhibition; Diagnostic test: Tests of sympathetic activation; Diagnostic test: Testing of autonomic dysreflexia; Device: Transcutaneous spinal cord stimulation

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02129
      • Spaulding Rehabilitation Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

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.; Device: Transcutaneous spinal cord stimulation; Transcutaneous spinal cord stimulation will be applied at T7-L1 spinal segments to assess alterations in autonomic neuroregulation.
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).; Device: Transcutaneous spinal cord stimulation; Transcutaneous spinal cord stimulation will be applied at T7-L1 spinal segments to assess alterations in autonomic neuroregulation.

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.	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

Collaborators and Investigators

• Sponsor: Spaulding Rehabilitation Hospital
• Collaborators: Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2022
• Primary Completion (Actual): November 14, 2022
• Study Completion (Actual): November 14, 2022

Study Registration Dates

• First Submitted: April 14, 2021
• First Submitted That Met QC Criteria: April 21, 2021
• First Posted (Actual): April 26, 2021

Study Record Updates

• Last Update Posted (Actual): April 14, 2023
• Last Update Submitted That Met QC Criteria: April 13, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Trauma, Nervous System; Spinal Cord Diseases; Autonomic Nervous System Diseases; Primary Dysautonomias; Orthostatic Intolerance; Hypotension; Spinal Cord Injuries; Hypotension, Orthostatic; Autonomic Dysreflexia
• Other Study ID Numbers: 2021P001100

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: Yes
• product manufactured in and exported from the U.S.: No