<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/NCT02983266</url>
  </required_header>
  <id_info>
    <org_study_id>20150478</org_study_id>
    <nct_id>NCT02983266</nct_id>
  </id_info>
  <brief_title>Vagal Nerve Stimulation to Reduce Inflammation and Hyperadrenergia</brief_title>
  <official_title>A Study of Safety and Autonomic Responses to Non-Invasive Vagal Stimulation in Persons With Spinal Cord Injury and Non-Disabled Controls Both With and Without Inflammatory Stress</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Miami</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Miami</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this research device study is to learn more about the autonomic nervous&#xD;
      system. This system uses nerves to send information from the brain to the rest of the body by&#xD;
      electrical signaling and has two divisions, the sympathetic and the parasympathetic branches.&#xD;
      It has been thought that electrical stimulation devices could be used to restore balance to&#xD;
      the nervous system. Because most of the imbalance seems to happen due to too much sympathetic&#xD;
      activity, the investigator plans to focus on the parasympathetic branch. Specifically, the&#xD;
      investigator hopes to restore balance by targeting the vagus nerve, which is the main&#xD;
      communicator of the parasympathetic branch. The study will examine whether the investigator&#xD;
      can decrease sympathetic activity and chronic inflammation by increasing parasympathetic&#xD;
      activity. This is a device study that will examine the use of non-invasive vagal nerve&#xD;
      stimulation to attenuate inflammatory stress and sympathetic hyperactivity in persons with&#xD;
      Spinal Cord Injury and Non-Disabled Controls.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Insufficient funding&#xD;
  </why_stopped>
  <start_date type="Anticipated">December 1, 2018</start_date>
  <completion_date type="Anticipated">December 1, 2020</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in parasympathetic activity after vagal nerve stimulation by Heart Rate Variability</measure>
    <time_frame>Baseline to 90 minutes post-vagal nerve stimulation</time_frame>
    <description>Measured by the normal-to-normal QRS complexes of the PQRST waveform of the electrocardiogram (ECG)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Group 1 &amp; 4: Change in acute heart rate response to vagal nerve stimulation</measure>
    <time_frame>Baseline to 90 minutes post-vagal nerve stimulation</time_frame>
    <description>Measured by numerical heart rate in beats per minute</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Group 1 &amp; 4: Change in acute blood pressure response to vagal nerve stimulation</measure>
    <time_frame>Baseline to 90 minutes post-vagal nerve stimulation</time_frame>
    <description>Measured by diastolic and systolic blood pressure (mm/Hg)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Group 1: Change in parasympathetic activity after vagal nerve stimulation by Vagus Somatosensory Evoked Potentials</measure>
    <time_frame>Baseline to 90 minutes post-vagal nerve stimulation</time_frame>
    <description>Measured by far field potentials from the brain stem</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Group 2 &amp; 4: Change in acute physiological stress response by a change in peripheral cortisol</measure>
    <time_frame>Baseline to 90 minutes post-experimental stimulus</time_frame>
    <description>Measured by cortisol levels in plasma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Group 2 &amp; 4: Change in acute physiological stress response by a change in peripheral catecholamines</measure>
    <time_frame>Baseline to 90 minutes post-experimental stimulus</time_frame>
    <description>Measured by catecholamine levels in plasma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Group 2 &amp; 4: Change in acute physiological stress response by a change in heart rate</measure>
    <time_frame>Baseline to 90 minutes post-experimental stimulus</time_frame>
    <description>Measured by numerical heart rate in beats per minute</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Group 2 &amp; 4: Change in acute physiological stress response by a change in blood pressure</measure>
    <time_frame>Baseline to 90 minutes post-experimental stimulus</time_frame>
    <description>Measured by diastolic and systolic blood pressure (mm/Hg)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Group 3 &amp; 4: Change in inflammatory biomarkers after vagal nerve stimulation</measure>
    <time_frame>Baseline to 90 minutes post-vagal nerve stimulation</time_frame>
    <description>Measured by cytokine levels in plasma</description>
  </secondary_outcome>
  <number_of_arms>9</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Spinal Cord Injury</condition>
  <arm_group>
    <arm_group_label>Group 1: Low Hertz</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive 10 hertz stimulation to the left auricular branch of the vagus nerve, delivered in one 15 minute session.&#xD;
Device: InTENsity MicroCombo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 1: High Hertz</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive 30 hertz stimulation to the left auricular branch of the vagus nerve, delivered in one 15 minute session.&#xD;
Device: InTENsity MicroCombo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 1: Control</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Participants will receive 30 hertz stimulation to a non-vagally innervated region of the left ear, delivered in one 15 minute session.&#xD;
Device: InTENsity MicroCombo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2: Pre-stressor</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive 10 or 30 hertz stimulation to the left auricular branch of the vagus nerve, delivered in one 15 minute session prior to receiving experimental sympathetic induction.&#xD;
Device: InTENsity MicroCombo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2: Post-stressor</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive 10 or 30 hertz stimulation to the left auricular branch of the vagus nerve, delivered in one 15 minute session after experimental sympathetic induction.&#xD;
Device: InTENsity MicroCombo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2: Control</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will receive 10 or 30 hertz stimulation to a non-vagally innervated region of the left ear, delivered in one 15 minute session prior to receiving experimental sympathetic induction.&#xD;
Device: InTENsity MicroCombo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 3: 30 Hz</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive 10 or 30 hertz stimulation to the left auricular branch of the vagus nerve, delivered in one 15 minute session.&#xD;
Device: InTENsity MicroCombo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 4: 30 Hz</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive 10 or 30 hertz stimulation to the left auricular branch of the vagus nerve, delivered in one 15 minute session. Participants will also receive stimulation on a subsequent session prior to urodynamic testing.&#xD;
Device: InTENsity MicroCombo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 1: Response</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive 10-30 hertz stimulation to the left auricular branch of the vagus nerve, delivered over the course of 1 hour.&#xD;
Device: InTENsity MicroCombo</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>InTENsity MicroCombo</intervention_name>
    <description>An electrotherapy device.</description>
    <arm_group_label>Group 1: Control</arm_group_label>
    <arm_group_label>Group 1: High Hertz</arm_group_label>
    <arm_group_label>Group 1: Low Hertz</arm_group_label>
    <arm_group_label>Group 1: Response</arm_group_label>
    <arm_group_label>Group 2: Control</arm_group_label>
    <arm_group_label>Group 2: Post-stressor</arm_group_label>
    <arm_group_label>Group 2: Pre-stressor</arm_group_label>
    <arm_group_label>Group 3: 30 Hz</arm_group_label>
    <arm_group_label>Group 4: 30 Hz</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Group 1 &amp; 2:&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 18-65&#xD;
&#xD;
          2. Willingness to participate in the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Use of an active electrical implant, such as a cardiac pacemaker or cochlear implant&#xD;
&#xD;
          2. Use of a hearing aid in the left ear&#xD;
&#xD;
          3. Use of an implanted insulin or morphine (pain) pump&#xD;
&#xD;
          4. Self-reported history of syncope from known or unknown origins&#xD;
&#xD;
          5. Self-reported history of cardiovascular disease or dysfunction (e.g., cardiovascular&#xD;
             disease, arrhythmia, congestive heart failure, or stroke)&#xD;
&#xD;
        Group 3:&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 18-65&#xD;
&#xD;
          2. Overweight, with a BMI ≥ 27&#xD;
&#xD;
          3. Presence of chronic inflammation, with C-reactive protein values &gt; 3 mg/l&#xD;
&#xD;
          4. Willingness to participate in the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Use of an active electrical implant, such as a cardiac pacemaker or cochlear implant&#xD;
&#xD;
          2. Use of a hearing aid in the left ear&#xD;
&#xD;
          3. Use of an implanted insulin or morphine (pain) pump&#xD;
&#xD;
          4. Self-reported history of syncope from known or unknown origins&#xD;
&#xD;
          5. Self-reported history of cardiovascular disease or dysfunction (e.g., cardiovascular&#xD;
             disease, arrhythmia, congestive heart failure, or stroke)&#xD;
&#xD;
          6. Use of statin drugs&#xD;
&#xD;
        Group 4:&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 18-65&#xD;
&#xD;
          2. ≥ 1-year post-injury&#xD;
&#xD;
          3. Bladder management by clean intermittent catheterization&#xD;
&#xD;
          4. Spinal cord injury resulting in Paraplegia level T1 to T6 and motor-complete (AIS A or&#xD;
             B) impairment. Injury level and impairment will be confirmed by an ASIA exam conducted&#xD;
             less than 2 years before study entry. If longer than 2 years, we will have a certified&#xD;
             rater repeat the exam.&#xD;
&#xD;
          5. Participant report of symptoms related to autonomic dysreflexia during episodes of&#xD;
             full bladder or voiding, including elevated BP, mild headache, paresthesia, chills,&#xD;
             nasal congestion, flushing of the skin, or diaphoresis.&#xD;
&#xD;
          6. Willingness to participate in the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Currently hospitalized&#xD;
&#xD;
          2. American Spinal Injury Association (AIS) C-E&#xD;
&#xD;
          3. Currently using an insulin, morphine (pain), or intrathecal pump&#xD;
&#xD;
          4. Use of an active electrical implant, such as a cardiac pacemaker or cochlear implant&#xD;
&#xD;
          5. Use of a hearing aid in the left ear&#xD;
&#xD;
          6. Self-reported history of syncope from known or unknown origins&#xD;
&#xD;
          7. Self-reported history of cardiovascular disease or dysfunction (e.g., cardiovascular&#xD;
             disease, arrhythmia, congestive heart failure, or stroke)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mark S Nash, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Miami</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The Miami Project to Cure Paralysis/ University of Miami</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>November 18, 2016</study_first_submitted>
  <study_first_submitted_qc>December 1, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 6, 2016</study_first_posted>
  <last_update_submitted>October 5, 2018</last_update_submitted>
  <last_update_submitted_qc>October 5, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 9, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Miami</investigator_affiliation>
    <investigator_full_name>Mark S. Nash, Ph.D., FACSM</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Hyperadrenergia</keyword>
  <keyword>Inflammatory stress</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Spinal Cord 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/NCT02983266
org study id: 20150478
nct id: NCT02983266
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is us export: No
The purpose of this research device study is to learn more about the autonomic nervous
      system. This system uses nerves to send information from the brain to the rest of the body by
      electrical signaling and has two divisions, the sympathetic and the parasympathetic branches.
      It has been thought that electrical stimulation devices could be used to restore balance to
      the nervous system. Because most of the imbalance seems to happen due to too much sympathetic
      activity, the investigator plans to focus on the parasympathetic branch. Specifically, the
      investigator hopes to restore balance by targeting the vagus nerve, which is the main
      communicator of the parasympathetic branch. The study will examine whether the investigator
      can decrease sympathetic activity and chronic inflammation by increasing parasympathetic
      activity. This is a device study that will examine the use of non-invasive vagal nerve
      stimulation to attenuate inflammatory stress and sympathetic hyperactivity in persons with
      Spinal Cord Injury and Non-Disabled Controls.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Single (Participant)
measure: Change in parasympathetic activity after vagal nerve stimulation by Heart Rate Variability
time frame: Baseline to 90 minutes post-vagal nerve stimulation
description: Measured by the normal-to-normal QRS complexes of the PQRST waveform of the electrocardiogram (ECG)
measure: Group 1 & 4: Change in acute heart rate response to vagal nerve stimulation
time frame: Baseline to 90 minutes post-vagal nerve stimulation
description: Measured by numerical heart rate in beats per minute
measure: Group 1 & 4: Change in acute blood pressure response to vagal nerve stimulation
time frame: Baseline to 90 minutes post-vagal nerve stimulation
description: Measured by diastolic and systolic blood pressure (mm/Hg)
measure: Group 1: Change in parasympathetic activity after vagal nerve stimulation by Vagus Somatosensory Evoked Potentials
time frame: Baseline to 90 minutes post-vagal nerve stimulation
description: Measured by far field potentials from the brain stem
measure: Group 2 & 4: Change in acute physiological stress response by a change in peripheral cortisol
time frame: Baseline to 90 minutes post-experimental stimulus
description: Measured by cortisol levels in plasma
measure: Group 2 & 4: Change in acute physiological stress response by a change in peripheral catecholamines
time frame: Baseline to 90 minutes post-experimental stimulus
description: Measured by catecholamine levels in plasma
measure: Group 2 & 4: Change in acute physiological stress response by a change in heart rate
time frame: Baseline to 90 minutes post-experimental stimulus
description: Measured by numerical heart rate in beats per minute
measure: Group 2 & 4: Change in acute physiological stress response by a change in blood pressure
time frame: Baseline to 90 minutes post-experimental stimulus
description: Measured by diastolic and systolic blood pressure (mm/Hg)
measure: Group 3 & 4: Change in inflammatory biomarkers after vagal nerve stimulation
time frame: Baseline to 90 minutes post-vagal nerve stimulation
description: Measured by cytokine levels in plasma
arm group label: Group 1: Low Hertz
arm group type: Experimental
description: Participants will receive 10 hertz stimulation to the left auricular branch of the vagus nerve, delivered in one 15 minute session.
Device: InTENsity MicroCombo
arm group label: Group 1: High Hertz
arm group type: Experimental
description: Participants will receive 30 hertz stimulation to the left auricular branch of the vagus nerve, delivered in one 15 minute session.
Device: InTENsity MicroCombo
arm group label: Group 1: Control
arm group type: Sham Comparator
description: Participants will receive 30 hertz stimulation to a non-vagally innervated region of the left ear, delivered in one 15 minute session.
Device: InTENsity MicroCombo
arm group label: Group 2: Pre-stressor
arm group type: Experimental
description: Participants will receive 10 or 30 hertz stimulation to the left auricular branch of the vagus nerve, delivered in one 15 minute session prior to receiving experimental sympathetic induction.
Device: InTENsity MicroCombo
arm group label: Group 2: Post-stressor
arm group type: Experimental
description: Participants will receive 10 or 30 hertz stimulation to the left auricular branch of the vagus nerve, delivered in one 15 minute session after experimental sympathetic induction.
Device: InTENsity MicroCombo
arm group label: Group 2: Control
arm group type: Placebo Comparator
description: Participants will receive 10 or 30 hertz stimulation to a non-vagally innervated region of the left ear, delivered in one 15 minute session prior to receiving experimental sympathetic induction.
Device: InTENsity MicroCombo
arm group label: Group 3: 30 Hz
arm group type: Experimental
description: Participants will receive 10 or 30 hertz stimulation to the left auricular branch of the vagus nerve, delivered in one 15 minute session.
Device: InTENsity MicroCombo
arm group label: Group 4: 30 Hz
arm group type: Experimental
description: Participants will receive 10 or 30 hertz stimulation to the left auricular branch of the vagus nerve, delivered in one 15 minute session. Participants will also receive stimulation on a subsequent session prior to urodynamic testing.
Device: InTENsity MicroCombo
arm group label: Group 1: Response
arm group type: Experimental
description: Participants will receive 10-30 hertz stimulation to the left auricular branch of the vagus nerve, delivered over the course of 1 hour.
Device: InTENsity MicroCombo
intervention type: Device
intervention name: InTENsity MicroCombo
description: An electrotherapy device.
arm group label: Group 1: Control
arm group label: Group 1: High Hertz
arm group label: Group 1: Low Hertz
arm group label: Group 1: Response
arm group label: Group 2: Control
arm group label: Group 2: Post-stressor
arm group label: Group 2: Pre-stressor
arm group label: Group 3: 30 Hz
arm group label: Group 4: 30 Hz
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Mark S Nash, Ph.D.
role: Principal Investigator
affiliation: University of Miami
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Miami
investigator full name: Mark S. Nash, Ph.D., FACSM
investigator title: Professor
mesh term: Spinal Cord Injuries
sharing ipd: No