Deciphering Preserved Autonomic Function After Spinal Cord Injury
Primary Purpose
Spinal Cord Injuries, Autonomic Imbalance, Autonomic Dysreflexia
Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Tests of sympathetic inhibition
Tests of sympathetic activation
Testing of autonomic dysreflexia
Sponsored by
About this trial
This is an interventional diagnostic trial for Spinal Cord Injuries
Eligibility Criteria
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.
Sites / Locations
- Spaulding Rehabilitation HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Individuals with spinal cord injury
Individuals without spinal cord injury
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Beat-to-beat heart rate
Electrocardiogram will record continuous measures with changes in R-R interval (ms) quantified and compared to baseline.
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.
Continuous galvanic skin response
Changes from resting state conductance with be quantified with a smartwatch.
Continuous wrist temperature
Changes from resting state temperature with be quantified with a smartwatch.
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).
Quantify secondary autonomic complications
Participants will be given the Composite Autonomic Symptom Score (range 0-100, with higher scores indicating more autonomic dysfunction).
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.
Full Information
NCT ID
NCT04493372
First Posted
July 17, 2020
Last Updated
June 20, 2022
Sponsor
Spaulding Rehabilitation Hospital
1. Study Identification
Unique Protocol Identification Number
NCT04493372
Brief Title
Deciphering Preserved Autonomic Function After Spinal Cord Injury
Official Title
Deciphering Preserved Autonomic Function After Spinal Cord Injury
Study Type
Interventional
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Recruiting
Study Start Date
November 13, 2020 (Actual)
Primary Completion Date
August 1, 2024 (Anticipated)
Study Completion Date
August 1, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Spaulding Rehabilitation Hospital
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spinal Cord Injuries, Autonomic Imbalance, Autonomic Dysreflexia, Orthostatic Hypotension
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
69 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Individuals with spinal cord injury
Arm Type
Experimental
Arm Title
Individuals without spinal cord injury
Arm Type
Experimental
Intervention Type
Diagnostic Test
Intervention Name(s)
Tests of sympathetic inhibition
Intervention Description
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.
Intervention Type
Diagnostic Test
Intervention Name(s)
Tests of sympathetic activation
Intervention Description
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).
Intervention Type
Diagnostic Test
Intervention Name(s)
Testing of autonomic dysreflexia
Intervention Description
Cold pressor test of the foot and bladder pressor response (in individuals with SCI) will be tested.
Primary Outcome Measure Information:
Title
Valsalva Maneuver Phase II
Description
Presence or absence of phase II on Valsalva maneuver testing, which takes approximately 15 seconds to complete. This will be repeated x3.
Time Frame
During laboratory diagnostic testing session
Secondary Outcome Measure Information:
Title
Muscle sympathetic nerve activity
Description
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.
Time Frame
During laboratory diagnostic testing session
Title
Beat-to-beat heart rate
Description
Electrocardiogram will record continuous measures with changes in R-R interval (ms) quantified and compared to baseline.
Time Frame
During laboratory diagnostic testing session
Title
Beat-to-beat blood pressure
Description
Non-invasive continuous blood pressure monitors will be used, with changes in systolic and diastolic pressure (in mmHg) from resting baseline measured.
Time Frame
During laboratory diagnostic testing session
Title
Continuous galvanic skin response
Description
Changes from resting state conductance with be quantified with a smartwatch.
Time Frame
During laboratory diagnostic testing session
Title
Continuous wrist temperature
Description
Changes from resting state temperature with be quantified with a smartwatch.
Time Frame
During laboratory diagnostic testing session
Title
Quantify autonomic dysreflexia and orthostatic hypotension
Description
Participants will be given the Autonomic Dysfunction Following Spinal Cord Injury questionnaire (score range 0-436, with higher scores indicating more autonomic dysfunction).
Time Frame
Baseline, prior to laboratory diagnostic testing session
Title
Quantify secondary autonomic complications
Description
Participants will be given the Composite Autonomic Symptom Score (range 0-100, with higher scores indicating more autonomic dysfunction).
Time Frame
Baseline, prior to laboratory diagnostic testing session
Title
Identify amplified functional connectivity within the spinal cord
Description
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.
Time Frame
During diagnostic imaging session
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
PI
Phone
16179525299
Email
rsolinsky@partners.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ryan Solinsky, MD
Organizational Affiliation
Spaulding Rehabilitation Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Spaulding Rehabilitation Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02129
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ryan Solinsky, MD
Email
rsolinsky@mgh.harvard.edu
12. IPD Sharing Statement
Plan to Share IPD
No
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Deciphering Preserved Autonomic Function After Spinal Cord Injury
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