<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04493372</url>
  </required_header>
  <id_info>
    <org_study_id>2020P001843</org_study_id>
    <nct_id>NCT04493372</nct_id>
  </id_info>
  <brief_title>Deciphering Preserved Autonomic Function After Spinal Cord Injury</brief_title>
  <official_title>Deciphering Preserved Autonomic Function After Spinal Cord Injury</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Spaulding Rehabilitation Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Spaulding Rehabilitation Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study looks to characterize gradients of dysfunction in the autonomic nervous system&#xD;
      after spinal cord injury. The autonomic nervous system plays key roles in regulation of blood&#xD;
      pressure, skin blood flow, and bladder health- all issues that individuals with spinal cord&#xD;
      injury typically suffer. Focusing on blood pressure regulation, the most precise metric with&#xD;
      broad clinical applicability, the investigators will perform a combination of laboratory,&#xD;
      ambulatory, and imaging-based tests to probe the body's ability to generate autonomic&#xD;
      responses. For both individuals with spinal cord injury and uninjured controls,&#xD;
      laboratory-based experiments will utilize multiple parallel recordings to identify how the&#xD;
      autonomic nervous system is able to inhibit and activate signals. The investigators&#xD;
      anticipate that those with autonomic dysfunction after spinal cord injury will exhibit&#xD;
      abnormalities in these precise metrics. The investigators will further have research&#xD;
      participants wear a smart watch that tracks skin electrical conductance, heart rate, and skin&#xD;
      temperature, which can all provide clues as to the degree of autonomic dysfunction someone&#xD;
      may suffer at home. The investigators will look to see if any substantial connections exist&#xD;
      between different degrees of preserved autonomic function and secondary autonomic&#xD;
      complications from spinal cord injury. Finally, functional magnetic resonance imaging scans&#xD;
      will be attained to characterize patterns of connectivity within the injured spinal cord. In&#xD;
      a similar manner, the investigators will look to see if different patterns of spinal cord&#xD;
      connectivity are more closely related to groupings of secondary autonomic complications. In&#xD;
      accomplishing this, the investigators hope to give scientists important insights to how the&#xD;
      autonomic nervous system works after spinal cord injury and give physicians better tools to&#xD;
      manage these secondary autonomic complications.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study looks to characterize gradients of dysfunction in the autonomic nervous system&#xD;
      after spinal cord injury. To accomplish this, we are enrolling both individuals with and&#xD;
      without spinal cord injuries (see inclusion criteria). Individuals will undergo the listed&#xD;
      diagnostics as part of a battery of laboratory testing. These will be correlated to clinical&#xD;
      histories of autonomic dysfunction the ADFSCI and COMPASS-31 surveys (noted in outcome&#xD;
      measures). Imaging-based tests will further probe the body's ability to generate autonomic&#xD;
      responses.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 13, 2020</start_date>
  <completion_date type="Anticipated">August 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">August 1, 2024</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Valsalva Maneuver Phase II</measure>
    <time_frame>During laboratory diagnostic testing session</time_frame>
    <description>Presence or absence of phase II on Valsalva maneuver testing, which takes approximately 15 seconds to complete. This will be repeated x3.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Muscle sympathetic nerve activity</measure>
    <time_frame>During laboratory diagnostic testing session</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Beat-to-beat heart rate</measure>
    <time_frame>During laboratory diagnostic testing session</time_frame>
    <description>Electrocardiogram will record continuous measures with changes in R-R interval (ms) quantified and compared to baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Beat-to-beat blood pressure</measure>
    <time_frame>During laboratory diagnostic testing session</time_frame>
    <description>Non-invasive continuous blood pressure monitors will be used, with changes in systolic and diastolic pressure (in mmHg) from resting baseline measured.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Continuous galvanic skin response</measure>
    <time_frame>During laboratory diagnostic testing session</time_frame>
    <description>Changes from resting state conductance with be quantified with a smartwatch.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Continuous wrist temperature</measure>
    <time_frame>During laboratory diagnostic testing session</time_frame>
    <description>Changes from resting state temperature with be quantified with a smartwatch.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quantify autonomic dysreflexia and orthostatic hypotension</measure>
    <time_frame>Baseline, prior to laboratory diagnostic testing session</time_frame>
    <description>Participants will be given the Autonomic Dysfunction Following Spinal Cord Injury questionnaire (score range 0-436, with higher scores indicating more autonomic dysfunction).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quantify secondary autonomic complications</measure>
    <time_frame>Baseline, prior to laboratory diagnostic testing session</time_frame>
    <description>Participants will be given the Composite Autonomic Symptom Score (range 0-100, with higher scores indicating more autonomic dysfunction).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Identify amplified functional connectivity within the spinal cord</measure>
    <time_frame>During diagnostic imaging session</time_frame>
    <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.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">69</enrollment>
  <condition>Spinal Cord Injuries</condition>
  <condition>Autonomic Imbalance</condition>
  <condition>Autonomic Dysreflexia</condition>
  <condition>Orthostatic Hypotension</condition>
  <arm_group>
    <arm_group_label>Individuals with spinal cord injury</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Individuals without spinal cord injury</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Tests of sympathetic inhibition</intervention_name>
    <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.</description>
    <arm_group_label>Individuals with spinal cord injury</arm_group_label>
    <arm_group_label>Individuals without spinal cord injury</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Tests of sympathetic activation</intervention_name>
    <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).</description>
    <arm_group_label>Individuals with spinal cord injury</arm_group_label>
    <arm_group_label>Individuals without spinal cord injury</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Testing of autonomic dysreflexia</intervention_name>
    <description>Cold pressor test of the foot and bladder pressor response (in individuals with SCI) will be tested.</description>
    <arm_group_label>Individuals with spinal cord injury</arm_group_label>
    <arm_group_label>Individuals without spinal cord injury</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        All subjects&#xD;
&#xD;
        - age 18-50 years old.&#xD;
&#xD;
        Participants with spinal cord injury&#xD;
&#xD;
          -  Adult onset, traumatic spinal cord injury.&#xD;
&#xD;
          -  Time since injury restricted to 1-5 years, in an effort to limit baroreflex&#xD;
             desensitization.&#xD;
&#xD;
          -  American Spinal Injury Association Impairment Scale, A-D, to encompass a spectrum of&#xD;
             autonomic dysfunction after spinal cord injury.&#xD;
&#xD;
          -  Neurological level of injury, C1-T12, as defined by the International Standards for&#xD;
             Neurological Classification of Spinal Cord Injury. Incorporating level of injury down&#xD;
             to T12 to encompass a broad range of autonomic dysfunction.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of cardiovascular disease, hypertension, neurologic disorders (with exception&#xD;
             of spinal cord injury), or diabetes.&#xD;
&#xD;
          -  Women who are pregnant or lactating.&#xD;
&#xD;
          -  Currently taking blood thinners.&#xD;
&#xD;
          -  Pacemaker, implanted defibrillator, or intrathecal pump incompatible with MRI&#xD;
             scanning.&#xD;
&#xD;
          -  Cognitive issues preventing informed consent for participation.&#xD;
&#xD;
          -  Body mass index &gt;30 kg/m2 for controls, in an effort to limit effects of early&#xD;
             cardiovascular disease and diabetes in control population. Body mass index has not&#xD;
             proven to be a good estimate of these factors following spinal cord injury.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ryan Solinsky, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Spaulding Rehabilitation Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>PI</last_name>
    <phone>16179525299</phone>
    <email>rsolinsky@partners.org</email>
  </overall_contact>
  <location>
    <facility>
      <name>Spaulding Rehabilitation Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02129</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ryan Solinsky, MD</last_name>
      <email>rsolinsky@mgh.harvard.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>July 17, 2020</study_first_submitted>
  <study_first_submitted_qc>July 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 30, 2020</study_first_posted>
  <last_update_submitted>June 20, 2022</last_update_submitted>
  <last_update_submitted_qc>June 20, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 24, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Spaulding Rehabilitation Hospital</investigator_affiliation>
    <investigator_full_name>Ryan Solinsky</investigator_full_name>
    <investigator_title>Clinician-Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Spinal Cord Injuries</mesh_term>
    <mesh_term>Hypotension, Orthostatic</mesh_term>
    <mesh_term>Autonomic Dysreflexia</mesh_term>
    <mesh_term>Hypotension</mesh_term>
    <mesh_term>Wounds and Injuries</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04493372
org study id: 2020P001843
nct id: NCT04493372
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
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.
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.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Valsalva Maneuver Phase II
time frame: During laboratory diagnostic testing session
description: Presence or absence of phase II on Valsalva maneuver testing, which takes approximately 15 seconds to complete. This will be repeated x3.
measure: Muscle sympathetic nerve activity
time frame: During laboratory diagnostic testing session
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.
measure: Beat-to-beat heart rate
time frame: During laboratory diagnostic testing session
description: Electrocardiogram will record continuous measures with changes in R-R interval (ms) quantified and compared to baseline.
measure: Beat-to-beat blood pressure
time frame: During laboratory diagnostic testing session
description: Non-invasive continuous blood pressure monitors will be used, with changes in systolic and diastolic pressure (in mmHg) from resting baseline measured.
measure: Continuous galvanic skin response
time frame: During laboratory diagnostic testing session
description: Changes from resting state conductance with be quantified with a smartwatch.
measure: Continuous wrist temperature
time frame: During laboratory diagnostic testing session
description: Changes from resting state temperature with be quantified with a smartwatch.
measure: Quantify autonomic dysreflexia and orthostatic hypotension
time frame: Baseline, prior to laboratory diagnostic testing session
description: Participants will be given the Autonomic Dysfunction Following Spinal Cord Injury questionnaire (score range 0-436, with higher scores indicating more autonomic dysfunction).
measure: Quantify secondary autonomic complications
time frame: Baseline, prior to laboratory diagnostic testing session
description: Participants will be given the Composite Autonomic Symptom Score (range 0-100, with higher scores indicating more autonomic dysfunction).
measure: Identify amplified functional connectivity within the spinal cord
time frame: During diagnostic imaging session
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.
arm group label: Individuals with spinal cord injury
arm group type: Experimental
arm group label: Individuals without spinal cord injury
arm group type: Experimental
intervention type: Diagnostic Test
intervention name: Tests of sympathetic inhibition
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.
arm group label: Individuals with spinal cord injury
arm group label: Individuals without spinal cord injury
intervention type: Diagnostic Test
intervention name: Tests of sympathetic activation
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).
arm group label: Individuals with spinal cord injury
arm group label: Individuals without spinal cord injury
intervention type: Diagnostic Test
intervention name: Testing of autonomic dysreflexia
description: Cold pressor test of the foot and bladder pressor response (in individuals with SCI) will be tested.
arm group label: Individuals with spinal cord injury
arm group label: Individuals without spinal cord injury
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Ryan Solinsky, MD
role: Principal Investigator
affiliation: Spaulding Rehabilitation Hospital
last name: PI
phone: 16179525299
email: rsolinsky@partners.org
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Spaulding Rehabilitation Hospital
investigator full name: Ryan Solinsky
investigator title: Clinician-Investigator
mesh term: Spinal Cord Injuries
mesh term: Hypotension, Orthostatic
mesh term: Autonomic Dysreflexia
mesh term: Hypotension
mesh term: Wounds and Injuries
sharing ipd: No