<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/NCT02992899</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00091171</org_study_id>
    <nct_id>NCT02992899</nct_id>
  </id_info>
  <brief_title>Closed Loop Vagal Nerve Stimulation for Patients With Posttraumatic Stress Disorder</brief_title>
  <official_title>Closed Loop Vagal Nerve Stimulation in Patients With Posttraumatic Stress Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Emory University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Georgia Institute of Technology</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Emory University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The tasks of the project are to map the potency and kinetics of the neurologic, autonomic&#xD;
      peripheral, inflammatory, and behavioral responses to vagal nerve stimulation (VNS) vs. sham&#xD;
      treatment, at baseline and in response to stressful traumatic scripts related to personal&#xD;
      traumatic events, as well as a series of other stressors.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this project is to develop the fundamental physiological understanding of&#xD;
      feedback controlled vagal nerve stimulation (VNS) using positron emission tomography (PET)&#xD;
      brain imaging and blood biomarker measurement with stress in healthy individuals and&#xD;
      individuals with PTSD. Healthy human subjects with a history of psychological trauma but&#xD;
      without the diagnosis of a psychiatric disorder (Phase 1), and human subjects with a history&#xD;
      of PTSD (Phase 2), undergo PET imaging of the brain in conjunction with VNS or a sham&#xD;
      treatment during exposure to neutral scripts and scripts of personal traumatic events. Blood&#xD;
      is drawn simultaneously for measurement of a variety of stress responsive biomarkers,&#xD;
      including inflammatory markers and neurohormones. A second PET scan with biomarkers assesses&#xD;
      the delayed effects of VNS. On two other days subjects undergo exposure to random stressors&#xD;
      with VNS or sham in conjunction with measurement of stress biomarkers.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 19, 2017</start_date>
  <completion_date type="Actual">September 21, 2019</completion_date>
  <primary_completion_date type="Actual">September 21, 2019</primary_completion_date>
  <phase>Phase 3</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>Other</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Level of Interleukin-6 (IL6)</measure>
    <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
    <description>IL6 level will be collected via blood draw. Change is defined as the difference in IL6 level from baseline to post emotional stress testing.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Level of Tryptophan</measure>
    <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
    <description>Tryptophan level will be collected via blood draw. Change is defined as the difference in tryptophan level from baseline to post emotional stress testing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of Kynurenine</measure>
    <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
    <description>Kynurenine level will be collected via blood draw. Change is defined as the difference in kynurenine level from baseline to post emotional stress testing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of Kynurenic Acid</measure>
    <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
    <description>Kynurenic acid level will be collected via blood draw. Change is defined as the difference in kynurenic acid level from baseline to post emotional stress testing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of 3-3 Hydroxykynurenine</measure>
    <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
    <description>3-3 hydroxykynurenine level will be collected via blood draw. Change is defined as the difference in 3-3 hydroxykynurenine level from baseline to post emotional stress testing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of Anthranilic Acid</measure>
    <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
    <description>Anthranilic Acid level will be collected via blood draw. Change is defined as the difference in anthranilic acid level from baseline to post emotional stress testing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of Tumor Necrosis Factor (TNF)-Alpha</measure>
    <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
    <description>TNF-alpha level will be collected via blood draw. Change is defined as the difference in TNF-alpha level from baseline to post emotional stress testing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of Interferon-Gamma</measure>
    <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
    <description>Interferon-Gamma level will be collected via blood draw. Change is defined as the difference in Interferon-Gamma level from baseline to post emotional stress testing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of Interleukin-1 Beta</measure>
    <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
    <description>Interleukin-1 Beta level will be collected via blood draw. Change is defined as the difference in Interleukin-1 Beta level from baseline to post emotional stress testing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of Interleukin-2 (IL2)</measure>
    <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
    <description>IL2 level will be collected via blood draw. Change is defined as the difference in IL2 level from baseline to post emotional stress testing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of Interleukin-4 (IL4)</measure>
    <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
    <description>IL4 level will be collected via blood draw. Change is defined as the difference in IL4 level from baseline to post emotional stress testing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of Interleukin-8 (IL8)</measure>
    <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
    <description>IL8 level will be collected via blood draw. Change is defined as the difference in IL8 level from baseline to post emotional stress testing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of Interleukin-10 (IL10)</measure>
    <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
    <description>IL10 level will be collected via blood draw. Change is defined as the difference in IL10 level from baseline to post emotional stress testing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of Interleukin-12p70 (IL12p70)</measure>
    <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
    <description>IL12p70 level will be collected via blood draw. Change is defined as the difference in IL12p70 level from baseline to post emotional stress testing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of Interleukin-12p (IL12p)</measure>
    <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
    <description>IL12p level will be collected via blood draw. Change is defined as the difference in IL12p level from baseline to post emotional stress testing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of Interleukin-13 (IL13)</measure>
    <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
    <description>IL13 level will be collected via blood draw. Change is defined as the difference in IL13 level from baseline to post emotional stress testing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of Macrophage Migration Inhibitory Factor</measure>
    <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
    <description>Macrophage migration inhibitory factor will be collected via blood draw. Change is defined as the difference in factor level from baseline to post emotional stress testing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of High-Mobility Group Protein B1</measure>
    <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
    <description>High-mobility group protein B1 level will be collected via blood draw. Change is defined as the difference in high-mobility group protein B1 level from baseline to post emotional stress testing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of Adrenocorticotropic Hormone</measure>
    <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
    <description>Adrenocorticotropic hormone level will be collected via blood draw. Change is defined as the difference in adrenocorticotropic hormone level from baseline to post emotional stress testing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of Cortisol</measure>
    <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
    <description>Cortisol level will be collected via blood draw. Change is defined as the difference in cortisol level from baseline to post emotional stress testing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of Epinephrine</measure>
    <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
    <description>Epinephrine level will be collected via blood draw. Change is defined as the difference in epinephrine level from baseline to post emotional stress testing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of Dopamine</measure>
    <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
    <description>Dopamine level will be collected via blood draw. Change is defined as the difference in dopamine level from baseline to post emotional stress testing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of Norepinephrine</measure>
    <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
    <description>Norepinephrine level will be collected via blood draw. Change is defined as the difference in norepinephrine level from baseline to post emotional stress testing.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">56</enrollment>
  <condition>PostTraumatic Stress Disorder</condition>
  <arm_group>
    <arm_group_label>Vagal Nerve Stimulation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants randomized to this arm will receive stimulation of the vagus nerve in conjunction with stress exposure.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham Stimulation</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Participants randomized to this arm will receive sham stimulation of the vagus nerve in conjunction with stress exposure.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>GammaCore/electroCore non-invasive VNS device</intervention_name>
    <description>Vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The intensity of the stimulus (the current amplitude) is adjusted by the user, to the maximum tolerable level to ensure VNS without causing excessive pain (typically 10-30 V), the burst frequency to 5 kilohertz (kHz), and the envelope frequency to 25 Hz. These are the standard frequency settings that electroCore has demonstrated to be most effective in capturing the vagus nerve based on evoked potential studies. The duration of delivery is 2 minutes, one minute into which the high-resolution positron emission tomography (HR-PET) scan is conducted; following an additional 8 minutes, a second VNS delivery is administered, after which another scan is obtained.</description>
    <arm_group_label>Vagal Nerve Stimulation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Sham gammaCore/electroCore</intervention_name>
    <description>Sham vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The device is programmed such that no actual stimulation is given to the vagus nerve. The duration of delivery is 2 minutes, one minute into which the HR-PET scan is conducted; following an additional 8 minutes, a second sham VNS delivery is administered, after which another scan is obtained.</description>
    <arm_group_label>Sham Stimulation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>O-15 water</intervention_name>
    <description>Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . H2[15O] will be prepared on-site in the Emory PET Center cyclotron. During the hours of the test, an intravenous infusion of normal saline will be started to permit the bolus injection of H2[15O]. Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
    <arm_group_label>Sham Stimulation</arm_group_label>
    <arm_group_label>Vagal Nerve Stimulation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Phase 1:&#xD;
&#xD;
          -  Do not meet criteria for post traumatic stress disorder (PTSD) or other major mental&#xD;
             disorder as determined by the Structured Clinical Interview for Diagnostic and&#xD;
             Statistical Manual of Mental Disorders-5 (DSM-5 SCID) interview for PTSD&#xD;
&#xD;
          -  Have a history of psychological trauma as defined by DSM-5.&#xD;
&#xD;
        Phase 2:&#xD;
&#xD;
        - Meet criteria for PTSD as determined by the Structured Clinical Interview for DSM-5&#xD;
        (SCID) interview for PTSD.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Positive pregnancy test&#xD;
&#xD;
          -  Meningitis&#xD;
&#xD;
          -  Traumatic brain injury&#xD;
&#xD;
          -  Neurological disorder or organic mental disorder&#xD;
&#xD;
          -  History of loss of consciousness greater than one minute&#xD;
&#xD;
          -  Alcohol abuse or substance abuse or dependence based on the SCID within the past 12&#xD;
             months&#xD;
&#xD;
          -  Positive toxicology screen&#xD;
&#xD;
          -  Current or lifetime history of schizophrenia, schizoaffective disorder, or bulimia,&#xD;
             based on the SCID&#xD;
&#xD;
          -  A history of serious medical or neurological illness, such as cardiovascular,&#xD;
             gastrointestinal, hepatic, renal, neurologic or other systemic illness&#xD;
&#xD;
          -  Evidence of a major medical or neurological illness on physical examination or as a&#xD;
             result of laboratory studies (complete blood count (CBC), blood urea nitrogen (BUN),&#xD;
             creatinine, blood sugar, electrolytes, liver and thyroid function tests, urinalysis,&#xD;
             and EKG)&#xD;
&#xD;
          -  Active implantable device (i.e. pacemaker)&#xD;
&#xD;
          -  Carotid atherosclerosis&#xD;
&#xD;
          -  Cervical vagotomy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>James D Bremner, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Emory University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Emory University</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>December 12, 2016</study_first_submitted>
  <study_first_submitted_qc>December 12, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 14, 2016</study_first_posted>
  <results_first_submitted>April 26, 2021</results_first_submitted>
  <results_first_submitted_qc>April 26, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">May 19, 2021</results_first_posted>
  <disposition_first_submitted>August 28, 2020</disposition_first_submitted>
  <disposition_first_submitted_qc>August 28, 2020</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">September 2, 2020</disposition_first_posted>
  <last_update_submitted>May 20, 2021</last_update_submitted>
  <last_update_submitted_qc>May 20, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 14, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Emory University</investigator_affiliation>
    <investigator_full_name>J. Douglas Bremner, MD</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>stress disorders, post-traumatic</keyword>
  <keyword>posttraumatic stress disorder</keyword>
  <keyword>PTSD</keyword>
  <keyword>vagal nerve</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stress Disorders, Traumatic</mesh_term>
    <mesh_term>Stress Disorders, Post-Traumatic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>August 8, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/99/NCT02992899/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Vagal Nerve Stimulation</title>
          <description>Participants randomized to this arm will receive stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
GammaCore/electroCore non-invasive VNS device: Vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The intensity of the stimulus is adjusted by the user, to the maximum tolerable level to ensure VNS without causing excessive pain (typically 10-30 V). The duration of delivery is 2 minutes, one minute into which the high-resolution positron emission tomography (HR-PET) scan is conducted; following an additional 8 minutes, a second VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
        </group>
        <group group_id="P2">
          <title>Sham Stimulation</title>
          <description>Participants randomized to this arm will receive sham stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
Sham gammaCore/electroCore: Sham vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The device is programmed such that no actual stimulation is given to the vagus nerve. The duration of delivery is 2 minutes, one minute into which the HR-PET scan is conducted; following an additional 8 minutes, a second sham VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . H2[15O] will be prepared on-site in the Emory PET Center cyclotron. During the hours of the test, an intravenous infusion of normal saline will be started to permit the bolus injection of H2[15O]. Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="27"/>
                <participants group_id="P2" count="29"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
                <participants group_id="P2" count="26"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Vagal Nerve Stimulation</title>
          <description>Participants randomized to this arm will receive stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
GammaCore/electroCore non-invasive VNS device: Vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The intensity of the stimulus is adjusted by the user, to the maximum tolerable level to ensure VNS without causing excessive pain (typically 10-30 V). The duration of delivery is 2 minutes, one minute into which the high-resolution positron emission tomography (HR-PET) scan is conducted; following an additional 8 minutes, a second VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
        </group>
        <group group_id="B2">
          <title>Sham Stimulation</title>
          <description>Participants randomized to this arm will receive sham stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
Sham gammaCore/electroCore: Sham vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The device is programmed such that no actual stimulation is given to the vagus nerve. The duration of delivery is 2 minutes, one minute into which the HR-PET scan is conducted; following an additional 8 minutes, a second sham VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . H2[15O] will be prepared on-site in the Emory PET Center cyclotron. During the hours of the test, an intravenous infusion of normal saline will be started to permit the bolus injection of H2[15O]. Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="27"/>
            <count group_id="B2" value="29"/>
            <count group_id="B3" value="56"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="31" spread="11"/>
                    <measurement group_id="B2" value="35" spread="11"/>
                    <measurement group_id="B3" value="33" spread="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="27"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Level of Interleukin-6 (IL6)</title>
        <description>IL6 level will be collected via blood draw. Change is defined as the difference in IL6 level from baseline to post emotional stress testing.</description>
        <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
        <population>Due to technical reasons and/or limited blood draw, the number of participants analyzed is less than the number of participants that completed the trial.</population>
        <group_list>
          <group group_id="O1">
            <title>Vagal Nerve Stimulation</title>
            <description>Participants randomized to this arm will receive stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
GammaCore/electroCore non-invasive VNS device: Vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The intensity of the stimulus is adjusted by the user, to the maximum tolerable level to ensure VNS without causing excessive pain (typically 10-30 V). The duration of delivery is 2 minutes, one minute into which the high-resolution positron emission tomography (HR-PET) scan is conducted; following an additional 8 minutes, a second VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
          <group group_id="O2">
            <title>Sham Stimulation</title>
            <description>Participants randomized to this arm will receive sham stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
Sham gammaCore/electroCore: Sham vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The device is programmed such that no actual stimulation is given to the vagus nerve. The duration of delivery is 2 minutes, one minute into which the HR-PET scan is conducted; following an additional 8 minutes, a second sham VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . H2[15O] will be prepared on-site in the Emory PET Center cyclotron. During the hours of the test, an intravenous infusion of normal saline will be started to permit the bolus injection of H2[15O]. Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
        </group_list>
        <measure>
          <title>Level of Interleukin-6 (IL6)</title>
          <description>IL6 level will be collected via blood draw. Change is defined as the difference in IL6 level from baseline to post emotional stress testing.</description>
          <population>Due to technical reasons and/or limited blood draw, the number of participants analyzed is less than the number of participants that completed the trial.</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline IL-6 Level</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.88" spread="0.59"/>
                    <measurement group_id="O2" value="0.84" spread="0.61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post Stress Testing IL-6 Level</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.77" spread="1.43"/>
                    <measurement group_id="O2" value="2.11" spread="2.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Level of Tryptophan</title>
        <description>Tryptophan level will be collected via blood draw. Change is defined as the difference in tryptophan level from baseline to post emotional stress testing.</description>
        <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
        <population>Due to technical reasons and/or limited blood draw, the number of participants analyzed is less than the number of participants that completed the trial.</population>
        <group_list>
          <group group_id="O1">
            <title>Vagal Nerve Stimulation</title>
            <description>Participants randomized to this arm will receive stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
GammaCore/electroCore non-invasive VNS device: Vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The intensity of the stimulus is adjusted by the user, to the maximum tolerable level to ensure VNS without causing excessive pain (typically 10-30 V). The duration of delivery is 2 minutes, one minute into which the high-resolution positron emission tomography (HR-PET) scan is conducted; following an additional 8 minutes, a second VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
          <group group_id="O2">
            <title>Sham Stimulation</title>
            <description>Participants randomized to this arm will receive sham stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
Sham gammaCore/electroCore: Sham vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The device is programmed such that no actual stimulation is given to the vagus nerve. The duration of delivery is 2 minutes, one minute into which the HR-PET scan is conducted; following an additional 8 minutes, a second sham VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . H2[15O] will be prepared on-site in the Emory PET Center cyclotron. During the hours of the test, an intravenous infusion of normal saline will be started to permit the bolus injection of H2[15O]. Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
        </group_list>
        <measure>
          <title>Level of Tryptophan</title>
          <description>Tryptophan level will be collected via blood draw. Change is defined as the difference in tryptophan level from baseline to post emotional stress testing.</description>
          <population>Due to technical reasons and/or limited blood draw, the number of participants analyzed is less than the number of participants that completed the trial.</population>
          <units>micromole/l</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline Tryptophan Level</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="50.59" spread="11.65"/>
                    <measurement group_id="O2" value="55.80" spread="15.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post Stress Testing Tryptophan Level</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="54.42" spread="13.21"/>
                    <measurement group_id="O2" value="57.79" spread="14.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Level of Kynurenine</title>
        <description>Kynurenine level will be collected via blood draw. Change is defined as the difference in kynurenine level from baseline to post emotional stress testing.</description>
        <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
        <population>Due to technical reasons and/or limited blood draw, the number of participants analyzed is less than the number of participants that completed the trial.</population>
        <group_list>
          <group group_id="O1">
            <title>Vagal Nerve Stimulation</title>
            <description>Participants randomized to this arm will receive stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
GammaCore/electroCore non-invasive VNS device: Vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The intensity of the stimulus is adjusted by the user, to the maximum tolerable level to ensure VNS without causing excessive pain (typically 10-30 V). The duration of delivery is 2 minutes, one minute into which the high-resolution positron emission tomography (HR-PET) scan is conducted; following an additional 8 minutes, a second VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
          <group group_id="O2">
            <title>Sham Stimulation</title>
            <description>Participants randomized to this arm will receive sham stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
Sham gammaCore/electroCore: Sham vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The device is programmed such that no actual stimulation is given to the vagus nerve. The duration of delivery is 2 minutes, one minute into which the HR-PET scan is conducted; following an additional 8 minutes, a second sham VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . H2[15O] will be prepared on-site in the Emory PET Center cyclotron. During the hours of the test, an intravenous infusion of normal saline will be started to permit the bolus injection of H2[15O]. Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
        </group_list>
        <measure>
          <title>Level of Kynurenine</title>
          <description>Kynurenine level will be collected via blood draw. Change is defined as the difference in kynurenine level from baseline to post emotional stress testing.</description>
          <population>Due to technical reasons and/or limited blood draw, the number of participants analyzed is less than the number of participants that completed the trial.</population>
          <units>µM</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline Kynurenine Level</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.72" spread="5.37"/>
                    <measurement group_id="O2" value="7.19" spread="5.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post Stress Testing Kynurenine Level</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.04" spread="5.81"/>
                    <measurement group_id="O2" value="7.06" spread="5.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Level of Kynurenic Acid</title>
        <description>Kynurenic acid level will be collected via blood draw. Change is defined as the difference in kynurenic acid level from baseline to post emotional stress testing.</description>
        <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
        <population>Due to technical reasons and/or limited blood draw, the number of participants analyzed is less than the number of participants that completed the trial.</population>
        <group_list>
          <group group_id="O1">
            <title>Vagal Nerve Stimulation</title>
            <description>Participants randomized to this arm will receive stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
GammaCore/electroCore non-invasive VNS device: Vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The intensity of the stimulus is adjusted by the user, to the maximum tolerable level to ensure VNS without causing excessive pain (typically 10-30 V). The duration of delivery is 2 minutes, one minute into which the high-resolution positron emission tomography (HR-PET) scan is conducted; following an additional 8 minutes, a second VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
          <group group_id="O2">
            <title>Sham Stimulation</title>
            <description>Participants randomized to this arm will receive sham stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
Sham gammaCore/electroCore: Sham vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The device is programmed such that no actual stimulation is given to the vagus nerve. The duration of delivery is 2 minutes, one minute into which the HR-PET scan is conducted; following an additional 8 minutes, a second sham VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . H2[15O] will be prepared on-site in the Emory PET Center cyclotron. During the hours of the test, an intravenous infusion of normal saline will be started to permit the bolus injection of H2[15O]. Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
        </group_list>
        <measure>
          <title>Level of Kynurenic Acid</title>
          <description>Kynurenic acid level will be collected via blood draw. Change is defined as the difference in kynurenic acid level from baseline to post emotional stress testing.</description>
          <population>Due to technical reasons and/or limited blood draw, the number of participants analyzed is less than the number of participants that completed the trial.</population>
          <units>pmol/100 microliters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline Kynurenic Acid Level</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.71" spread="9.59"/>
                    <measurement group_id="O2" value="43.07" spread="21.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post Stress Testing Kynurenic Acid Level</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="38.81" spread="16.50"/>
                    <measurement group_id="O2" value="37.88" spread="12.37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Level of 3-3 Hydroxykynurenine</title>
        <description>3-3 hydroxykynurenine level will be collected via blood draw. Change is defined as the difference in 3-3 hydroxykynurenine level from baseline to post emotional stress testing.</description>
        <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
        <population>This outcome was not assessed due to a lack of resources and a focus on other pertinent biomarkers per the literature.</population>
        <group_list>
          <group group_id="O1">
            <title>Vagal Nerve Stimulation</title>
            <description>Participants randomized to this arm will receive stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
GammaCore/electroCore non-invasive VNS device: Vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The intensity of the stimulus is adjusted by the user, to the maximum tolerable level to ensure VNS without causing excessive pain (typically 10-30 V). The duration of delivery is 2 minutes, one minute into which the high-resolution positron emission tomography (HR-PET) scan is conducted; following an additional 8 minutes, a second VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
          <group group_id="O2">
            <title>Sham Stimulation</title>
            <description>Participants randomized to this arm will receive sham stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
Sham gammaCore/electroCore: Sham vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The device is programmed such that no actual stimulation is given to the vagus nerve. The duration of delivery is 2 minutes, one minute into which the HR-PET scan is conducted; following an additional 8 minutes, a second sham VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . H2[15O] will be prepared on-site in the Emory PET Center cyclotron. During the hours of the test, an intravenous infusion of normal saline will be started to permit the bolus injection of H2[15O]. Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
        </group_list>
        <measure>
          <title>Level of 3-3 Hydroxykynurenine</title>
          <description>3-3 hydroxykynurenine level will be collected via blood draw. Change is defined as the difference in 3-3 hydroxykynurenine level from baseline to post emotional stress testing.</description>
          <population>This outcome was not assessed due to a lack of resources and a focus on other pertinent biomarkers per the literature.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Level of Anthranilic Acid</title>
        <description>Anthranilic Acid level will be collected via blood draw. Change is defined as the difference in anthranilic acid level from baseline to post emotional stress testing.</description>
        <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
        <population>Due to technical reasons and/or limited blood draw, the number of participants analyzed is less than the number of participants that completed the trial.</population>
        <group_list>
          <group group_id="O1">
            <title>Vagal Nerve Stimulation</title>
            <description>Participants randomized to this arm will receive stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
GammaCore/electroCore non-invasive VNS device: Vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The intensity of the stimulus is adjusted by the user, to the maximum tolerable level to ensure VNS without causing excessive pain (typically 10-30 V). The duration of delivery is 2 minutes, one minute into which the high-resolution positron emission tomography (HR-PET) scan is conducted; following an additional 8 minutes, a second VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
          <group group_id="O2">
            <title>Sham Stimulation</title>
            <description>Participants randomized to this arm will receive sham stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
Sham gammaCore/electroCore: Sham vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The device is programmed such that no actual stimulation is given to the vagus nerve. The duration of delivery is 2 minutes, one minute into which the HR-PET scan is conducted; following an additional 8 minutes, a second sham VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . H2[15O] will be prepared on-site in the Emory PET Center cyclotron. During the hours of the test, an intravenous infusion of normal saline will be started to permit the bolus injection of H2[15O]. Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
        </group_list>
        <measure>
          <title>Level of Anthranilic Acid</title>
          <description>Anthranilic Acid level will be collected via blood draw. Change is defined as the difference in anthranilic acid level from baseline to post emotional stress testing.</description>
          <population>Due to technical reasons and/or limited blood draw, the number of participants analyzed is less than the number of participants that completed the trial.</population>
          <units>nM</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline Anthranilic Acid Level</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.32" spread="2.68"/>
                    <measurement group_id="O2" value="7.02" spread="1.68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post Stress Testing Anthranilic Acid Level</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.49" spread="2.13"/>
                    <measurement group_id="O2" value="6.90" spread="1.59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Level of Tumor Necrosis Factor (TNF)-Alpha</title>
        <description>TNF-alpha level will be collected via blood draw. Change is defined as the difference in TNF-alpha level from baseline to post emotional stress testing.</description>
        <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
        <population>Due to technical reasons and/or limited blood draw, the number of participants analyzed is less than the number of participants that completed the trial.</population>
        <group_list>
          <group group_id="O1">
            <title>Vagal Nerve Stimulation</title>
            <description>Participants randomized to this arm will receive stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
GammaCore/electroCore non-invasive VNS device: Vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The intensity of the stimulus is adjusted by the user, to the maximum tolerable level to ensure VNS without causing excessive pain (typically 10-30 V). The duration of delivery is 2 minutes, one minute into which the high-resolution positron emission tomography (HR-PET) scan is conducted; following an additional 8 minutes, a second VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
          <group group_id="O2">
            <title>Sham Stimulation</title>
            <description>Participants randomized to this arm will receive sham stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
Sham gammaCore/electroCore: Sham vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The device is programmed such that no actual stimulation is given to the vagus nerve. The duration of delivery is 2 minutes, one minute into which the HR-PET scan is conducted; following an additional 8 minutes, a second sham VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . H2[15O] will be prepared on-site in the Emory PET Center cyclotron. During the hours of the test, an intravenous infusion of normal saline will be started to permit the bolus injection of H2[15O]. Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
        </group_list>
        <measure>
          <title>Level of Tumor Necrosis Factor (TNF)-Alpha</title>
          <description>TNF-alpha level will be collected via blood draw. Change is defined as the difference in TNF-alpha level from baseline to post emotional stress testing.</description>
          <population>Due to technical reasons and/or limited blood draw, the number of participants analyzed is less than the number of participants that completed the trial.</population>
          <units>pg/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline Tumor Necrosis Factor (TNF)-alpha Level</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.81" spread="1.28"/>
                    <measurement group_id="O2" value="2.37" spread="0.87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post Stress Testing Tumor Necrosis Factor (TNF)-alpha Level</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.63" spread="1.03"/>
                    <measurement group_id="O2" value="2.26" spread="0.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Level of Interferon-Gamma</title>
        <description>Interferon-Gamma level will be collected via blood draw. Change is defined as the difference in Interferon-Gamma level from baseline to post emotional stress testing.</description>
        <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
        <population>Due to technical reasons and/or limited blood draw, the number of participants analyzed is less than the number of participants that completed the trial.</population>
        <group_list>
          <group group_id="O1">
            <title>Vagal Nerve Stimulation</title>
            <description>Participants randomized to this arm will receive stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
GammaCore/electroCore non-invasive VNS device: Vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The intensity of the stimulus is adjusted by the user, to the maximum tolerable level to ensure VNS without causing excessive pain (typically 10-30 V). The duration of delivery is 2 minutes, one minute into which the high-resolution positron emission tomography (HR-PET) scan is conducted; following an additional 8 minutes, a second VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
          <group group_id="O2">
            <title>Sham Stimulation</title>
            <description>Participants randomized to this arm will receive sham stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
Sham gammaCore/electroCore: Sham vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The device is programmed such that no actual stimulation is given to the vagus nerve. The duration of delivery is 2 minutes, one minute into which the HR-PET scan is conducted; following an additional 8 minutes, a second sham VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . H2[15O] will be prepared on-site in the Emory PET Center cyclotron. During the hours of the test, an intravenous infusion of normal saline will be started to permit the bolus injection of H2[15O]. Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
        </group_list>
        <measure>
          <title>Level of Interferon-Gamma</title>
          <description>Interferon-Gamma level will be collected via blood draw. Change is defined as the difference in Interferon-Gamma level from baseline to post emotional stress testing.</description>
          <population>Due to technical reasons and/or limited blood draw, the number of participants analyzed is less than the number of participants that completed the trial.</population>
          <units>pg/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline Interferon-Gamma Level</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.75" spread="9.61"/>
                    <measurement group_id="O2" value="3.43" spread="2.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post Stress Testing Interferon-Gamma Level</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.86" spread="10.20"/>
                    <measurement group_id="O2" value="8.87" spread="27.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Level of Interleukin-1 Beta</title>
        <description>Interleukin-1 Beta level will be collected via blood draw. Change is defined as the difference in Interleukin-1 Beta level from baseline to post emotional stress testing.</description>
        <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
        <population>Due to technical reasons and/or limited blood draw, the number of participants analyzed is less than the number of participants that completed the trial.</population>
        <group_list>
          <group group_id="O1">
            <title>Vagal Nerve Stimulation</title>
            <description>Participants randomized to this arm will receive stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
GammaCore/electroCore non-invasive VNS device: Vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The intensity of the stimulus is adjusted by the user, to the maximum tolerable level to ensure VNS without causing excessive pain (typically 10-30 V). The duration of delivery is 2 minutes, one minute into which the high-resolution positron emission tomography (HR-PET) scan is conducted; following an additional 8 minutes, a second VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
          <group group_id="O2">
            <title>Sham Stimulation</title>
            <description>Participants randomized to this arm will receive sham stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
Sham gammaCore/electroCore: Sham vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The device is programmed such that no actual stimulation is given to the vagus nerve. The duration of delivery is 2 minutes, one minute into which the HR-PET scan is conducted; following an additional 8 minutes, a second sham VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . H2[15O] will be prepared on-site in the Emory PET Center cyclotron. During the hours of the test, an intravenous infusion of normal saline will be started to permit the bolus injection of H2[15O]. Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
        </group_list>
        <measure>
          <title>Level of Interleukin-1 Beta</title>
          <description>Interleukin-1 Beta level will be collected via blood draw. Change is defined as the difference in Interleukin-1 Beta level from baseline to post emotional stress testing.</description>
          <population>Due to technical reasons and/or limited blood draw, the number of participants analyzed is less than the number of participants that completed the trial.</population>
          <units>pg/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline Interleukin-1 Beta Level</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.056" spread="0.033"/>
                    <measurement group_id="O2" value="0.086" spread="0.056"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post Stress Testing Interleukin-1 Beta Level</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.071" spread="0.041"/>
                    <measurement group_id="O2" value="0.085" spread="0.077"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Level of Interleukin-2 (IL2)</title>
        <description>IL2 level will be collected via blood draw. Change is defined as the difference in IL2 level from baseline to post emotional stress testing.</description>
        <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
        <population>Due to technical reasons and/or limited blood draw, the number of participants analyzed is less than the number of participants that completed the trial.</population>
        <group_list>
          <group group_id="O1">
            <title>Vagal Nerve Stimulation</title>
            <description>Participants randomized to this arm will receive stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
GammaCore/electroCore non-invasive VNS device: Vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The intensity of the stimulus is adjusted by the user, to the maximum tolerable level to ensure VNS without causing excessive pain (typically 10-30 V). The duration of delivery is 2 minutes, one minute into which the high-resolution positron emission tomography (HR-PET) scan is conducted; following an additional 8 minutes, a second VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
          <group group_id="O2">
            <title>Sham Stimulation</title>
            <description>Participants randomized to this arm will receive sham stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
Sham gammaCore/electroCore: Sham vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The device is programmed such that no actual stimulation is given to the vagus nerve. The duration of delivery is 2 minutes, one minute into which the HR-PET scan is conducted; following an additional 8 minutes, a second sham VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . H2[15O] will be prepared on-site in the Emory PET Center cyclotron. During the hours of the test, an intravenous infusion of normal saline will be started to permit the bolus injection of H2[15O]. Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
        </group_list>
        <measure>
          <title>Level of Interleukin-2 (IL2)</title>
          <description>IL2 level will be collected via blood draw. Change is defined as the difference in IL2 level from baseline to post emotional stress testing.</description>
          <population>Due to technical reasons and/or limited blood draw, the number of participants analyzed is less than the number of participants that completed the trial.</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline Interleukin-2 (IL2) Level</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.29" spread="0.22"/>
                    <measurement group_id="O2" value="0.29" spread="0.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post Stress Testing Interleukin-2 (IL2) Level</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.36" spread="0.20"/>
                    <measurement group_id="O2" value="0.27" spread="0.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Level of Interleukin-4 (IL4)</title>
        <description>IL4 level will be collected via blood draw. Change is defined as the difference in IL4 level from baseline to post emotional stress testing.</description>
        <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
        <population>This outcome was not assessed due to a lack of resources and a focus on other pertinent biomarkers per the literature.</population>
        <group_list>
          <group group_id="O1">
            <title>Vagal Nerve Stimulation</title>
            <description>Participants randomized to this arm will receive stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
GammaCore/electroCore non-invasive VNS device: Vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The intensity of the stimulus is adjusted by the user, to the maximum tolerable level to ensure VNS without causing excessive pain (typically 10-30 V). The duration of delivery is 2 minutes, one minute into which the high-resolution positron emission tomography (HR-PET) scan is conducted; following an additional 8 minutes, a second VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
          <group group_id="O2">
            <title>Sham Stimulation</title>
            <description>Participants randomized to this arm will receive sham stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
Sham gammaCore/electroCore: Sham vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The device is programmed such that no actual stimulation is given to the vagus nerve. The duration of delivery is 2 minutes, one minute into which the HR-PET scan is conducted; following an additional 8 minutes, a second sham VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . H2[15O] will be prepared on-site in the Emory PET Center cyclotron. During the hours of the test, an intravenous infusion of normal saline will be started to permit the bolus injection of H2[15O]. Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
        </group_list>
        <measure>
          <title>Level of Interleukin-4 (IL4)</title>
          <description>IL4 level will be collected via blood draw. Change is defined as the difference in IL4 level from baseline to post emotional stress testing.</description>
          <population>This outcome was not assessed due to a lack of resources and a focus on other pertinent biomarkers per the literature.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Level of Interleukin-8 (IL8)</title>
        <description>IL8 level will be collected via blood draw. Change is defined as the difference in IL8 level from baseline to post emotional stress testing.</description>
        <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
        <population>This outcome was not assessed due to a lack of resources and a focus on other pertinent biomarkers per the literature.</population>
        <group_list>
          <group group_id="O1">
            <title>Vagal Nerve Stimulation</title>
            <description>Participants randomized to this arm will receive stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
GammaCore/electroCore non-invasive VNS device: Vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The intensity of the stimulus is adjusted by the user, to the maximum tolerable level to ensure VNS without causing excessive pain (typically 10-30 V). The duration of delivery is 2 minutes, one minute into which the high-resolution positron emission tomography (HR-PET) scan is conducted; following an additional 8 minutes, a second VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
          <group group_id="O2">
            <title>Sham Stimulation</title>
            <description>Participants randomized to this arm will receive sham stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
Sham gammaCore/electroCore: Sham vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The device is programmed such that no actual stimulation is given to the vagus nerve. The duration of delivery is 2 minutes, one minute into which the HR-PET scan is conducted; following an additional 8 minutes, a second sham VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . H2[15O] will be prepared on-site in the Emory PET Center cyclotron. During the hours of the test, an intravenous infusion of normal saline will be started to permit the bolus injection of H2[15O]. Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
        </group_list>
        <measure>
          <title>Level of Interleukin-8 (IL8)</title>
          <description>IL8 level will be collected via blood draw. Change is defined as the difference in IL8 level from baseline to post emotional stress testing.</description>
          <population>This outcome was not assessed due to a lack of resources and a focus on other pertinent biomarkers per the literature.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Level of Interleukin-10 (IL10)</title>
        <description>IL10 level will be collected via blood draw. Change is defined as the difference in IL10 level from baseline to post emotional stress testing.</description>
        <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
        <population>This outcome was not assessed due to a lack of resources and a focus on other pertinent biomarkers per the literature.</population>
        <group_list>
          <group group_id="O1">
            <title>Vagal Nerve Stimulation</title>
            <description>Participants randomized to this arm will receive stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
GammaCore/electroCore non-invasive VNS device: Vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The intensity of the stimulus is adjusted by the user, to the maximum tolerable level to ensure VNS without causing excessive pain (typically 10-30 V). The duration of delivery is 2 minutes, one minute into which the high-resolution positron emission tomography (HR-PET) scan is conducted; following an additional 8 minutes, a second VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
          <group group_id="O2">
            <title>Sham Stimulation</title>
            <description>Participants randomized to this arm will receive sham stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
Sham gammaCore/electroCore: Sham vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The device is programmed such that no actual stimulation is given to the vagus nerve. The duration of delivery is 2 minutes, one minute into which the HR-PET scan is conducted; following an additional 8 minutes, a second sham VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . H2[15O] will be prepared on-site in the Emory PET Center cyclotron. During the hours of the test, an intravenous infusion of normal saline will be started to permit the bolus injection of H2[15O]. Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
        </group_list>
        <measure>
          <title>Level of Interleukin-10 (IL10)</title>
          <description>IL10 level will be collected via blood draw. Change is defined as the difference in IL10 level from baseline to post emotional stress testing.</description>
          <population>This outcome was not assessed due to a lack of resources and a focus on other pertinent biomarkers per the literature.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Level of Interleukin-12p70 (IL12p70)</title>
        <description>IL12p70 level will be collected via blood draw. Change is defined as the difference in IL12p70 level from baseline to post emotional stress testing.</description>
        <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
        <population>Due to technical reasons and/or limited blood draw, the number of participants analyzed is less than the number of participants that completed the trial.</population>
        <group_list>
          <group group_id="O1">
            <title>Vagal Nerve Stimulation</title>
            <description>Participants randomized to this arm will receive stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
GammaCore/electroCore non-invasive VNS device: Vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The intensity of the stimulus is adjusted by the user, to the maximum tolerable level to ensure VNS without causing excessive pain (typically 10-30 V). The duration of delivery is 2 minutes, one minute into which the high-resolution positron emission tomography (HR-PET) scan is conducted; following an additional 8 minutes, a second VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
          <group group_id="O2">
            <title>Sham Stimulation</title>
            <description>Participants randomized to this arm will receive sham stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
Sham gammaCore/electroCore: Sham vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The device is programmed such that no actual stimulation is given to the vagus nerve. The duration of delivery is 2 minutes, one minute into which the HR-PET scan is conducted; following an additional 8 minutes, a second sham VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . H2[15O] will be prepared on-site in the Emory PET Center cyclotron. During the hours of the test, an intravenous infusion of normal saline will be started to permit the bolus injection of H2[15O]. Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
        </group_list>
        <measure>
          <title>Level of Interleukin-12p70 (IL12p70)</title>
          <description>IL12p70 level will be collected via blood draw. Change is defined as the difference in IL12p70 level from baseline to post emotional stress testing.</description>
          <population>Due to technical reasons and/or limited blood draw, the number of participants analyzed is less than the number of participants that completed the trial.</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline Interleukin-12p70 (IL12p70) Level Level</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.20" spread="1.48"/>
                    <measurement group_id="O2" value="3.22" spread="1.68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post Stress Testing Interleukin-12p70 (IL12p70) Level Level</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.82" spread="0.99"/>
                    <measurement group_id="O2" value="2.96" spread="2.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Level of Interleukin-12p (IL12p)</title>
        <description>IL12p level will be collected via blood draw. Change is defined as the difference in IL12p level from baseline to post emotional stress testing.</description>
        <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
        <population>This outcome was not assessed due to a lack of resources and a focus on other pertinent biomarkers per the literature.</population>
        <group_list>
          <group group_id="O1">
            <title>Vagal Nerve Stimulation</title>
            <description>Participants randomized to this arm will receive stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
GammaCore/electroCore non-invasive VNS device: Vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The intensity of the stimulus is adjusted by the user, to the maximum tolerable level to ensure VNS without causing excessive pain (typically 10-30 V). The duration of delivery is 2 minutes, one minute into which the high-resolution positron emission tomography (HR-PET) scan is conducted; following an additional 8 minutes, a second VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
          <group group_id="O2">
            <title>Sham Stimulation</title>
            <description>Participants randomized to this arm will receive sham stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
Sham gammaCore/electroCore: Sham vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The device is programmed such that no actual stimulation is given to the vagus nerve. The duration of delivery is 2 minutes, one minute into which the HR-PET scan is conducted; following an additional 8 minutes, a second sham VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . H2[15O] will be prepared on-site in the Emory PET Center cyclotron. During the hours of the test, an intravenous infusion of normal saline will be started to permit the bolus injection of H2[15O]. Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
        </group_list>
        <measure>
          <title>Level of Interleukin-12p (IL12p)</title>
          <description>IL12p level will be collected via blood draw. Change is defined as the difference in IL12p level from baseline to post emotional stress testing.</description>
          <population>This outcome was not assessed due to a lack of resources and a focus on other pertinent biomarkers per the literature.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Level of Interleukin-13 (IL13)</title>
        <description>IL13 level will be collected via blood draw. Change is defined as the difference in IL13 level from baseline to post emotional stress testing.</description>
        <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
        <population>Due to technical reasons and/or limited blood draw, the number of participants analyzed is less than the number of participants that completed the trial.</population>
        <group_list>
          <group group_id="O1">
            <title>Vagal Nerve Stimulation</title>
            <description>Participants randomized to this arm will receive stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
GammaCore/electroCore non-invasive VNS device: Vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The intensity of the stimulus is adjusted by the user, to the maximum tolerable level to ensure VNS without causing excessive pain (typically 10-30 V). The duration of delivery is 2 minutes, one minute into which the high-resolution positron emission tomography (HR-PET) scan is conducted; following an additional 8 minutes, a second VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
          <group group_id="O2">
            <title>Sham Stimulation</title>
            <description>Participants randomized to this arm will receive sham stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
Sham gammaCore/electroCore: Sham vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The device is programmed such that no actual stimulation is given to the vagus nerve. The duration of delivery is 2 minutes, one minute into which the HR-PET scan is conducted; following an additional 8 minutes, a second sham VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . H2[15O] will be prepared on-site in the Emory PET Center cyclotron. During the hours of the test, an intravenous infusion of normal saline will be started to permit the bolus injection of H2[15O]. Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
        </group_list>
        <measure>
          <title>Level of Interleukin-13 (IL13)</title>
          <description>IL13 level will be collected via blood draw. Change is defined as the difference in IL13 level from baseline to post emotional stress testing.</description>
          <population>Due to technical reasons and/or limited blood draw, the number of participants analyzed is less than the number of participants that completed the trial.</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline Interleukin-13 (IL13) Level</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.77" spread="16.87"/>
                    <measurement group_id="O2" value="43.10" spread="18.78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post Stress Testing Interleukin-13 (IL13) Level</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.17" spread="14.03"/>
                    <measurement group_id="O2" value="43.55" spread="31.91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Level of Macrophage Migration Inhibitory Factor</title>
        <description>Macrophage migration inhibitory factor will be collected via blood draw. Change is defined as the difference in factor level from baseline to post emotional stress testing.</description>
        <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
        <population>Due to technical reasons and/or limited blood draw, the number of participants analyzed is less than the number of participants that completed the trial.</population>
        <group_list>
          <group group_id="O1">
            <title>Vagal Nerve Stimulation</title>
            <description>Participants randomized to this arm will receive stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
GammaCore/electroCore non-invasive VNS device: Vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The intensity of the stimulus is adjusted by the user, to the maximum tolerable level to ensure VNS without causing excessive pain (typically 10-30 V). The duration of delivery is 2 minutes, one minute into which the high-resolution positron emission tomography (HR-PET) scan is conducted; following an additional 8 minutes, a second VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
          <group group_id="O2">
            <title>Sham Stimulation</title>
            <description>Participants randomized to this arm will receive sham stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
Sham gammaCore/electroCore: Sham vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The device is programmed such that no actual stimulation is given to the vagus nerve. The duration of delivery is 2 minutes, one minute into which the HR-PET scan is conducted; following an additional 8 minutes, a second sham VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . H2[15O] will be prepared on-site in the Emory PET Center cyclotron. During the hours of the test, an intravenous infusion of normal saline will be started to permit the bolus injection of H2[15O]. Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
        </group_list>
        <measure>
          <title>Level of Macrophage Migration Inhibitory Factor</title>
          <description>Macrophage migration inhibitory factor will be collected via blood draw. Change is defined as the difference in factor level from baseline to post emotional stress testing.</description>
          <population>Due to technical reasons and/or limited blood draw, the number of participants analyzed is less than the number of participants that completed the trial.</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline Macrophage Migration Inhibitory Factor Level</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32,204" spread="14,130"/>
                    <measurement group_id="O2" value="31,309" spread="20,624"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post Stress Testing Macrophage Migration Inhibitory Factor Level</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30,403" spread="14,007"/>
                    <measurement group_id="O2" value="30,515" spread="17,399"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Level of High-Mobility Group Protein B1</title>
        <description>High-mobility group protein B1 level will be collected via blood draw. Change is defined as the difference in high-mobility group protein B1 level from baseline to post emotional stress testing.</description>
        <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
        <population>Due to technical reasons and/or limited blood draw, the number of participants analyzed is less than the number of participants that completed the trial.</population>
        <group_list>
          <group group_id="O1">
            <title>Vagal Nerve Stimulation</title>
            <description>Participants randomized to this arm will receive stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
GammaCore/electroCore non-invasive VNS device: Vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The intensity of the stimulus is adjusted by the user, to the maximum tolerable level to ensure VNS without causing excessive pain (typically 10-30 V). The duration of delivery is 2 minutes, one minute into which the high-resolution positron emission tomography (HR-PET) scan is conducted; following an additional 8 minutes, a second VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
          <group group_id="O2">
            <title>Sham Stimulation</title>
            <description>Participants randomized to this arm will receive sham stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
Sham gammaCore/electroCore: Sham vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The device is programmed such that no actual stimulation is given to the vagus nerve. The duration of delivery is 2 minutes, one minute into which the HR-PET scan is conducted; following an additional 8 minutes, a second sham VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . H2[15O] will be prepared on-site in the Emory PET Center cyclotron. During the hours of the test, an intravenous infusion of normal saline will be started to permit the bolus injection of H2[15O]. Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
        </group_list>
        <measure>
          <title>Level of High-Mobility Group Protein B1</title>
          <description>High-mobility group protein B1 level will be collected via blood draw. Change is defined as the difference in high-mobility group protein B1 level from baseline to post emotional stress testing.</description>
          <population>Due to technical reasons and/or limited blood draw, the number of participants analyzed is less than the number of participants that completed the trial.</population>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline High-Mobility Group Protein B1 Level</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1,552" spread="1,105"/>
                    <measurement group_id="O2" value="1,734" spread="893"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post Stress Testing High-Mobility Group Protein B1 Level</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1,299" spread="574"/>
                    <measurement group_id="O2" value="1,691" spread="942"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Level of Adrenocorticotropic Hormone</title>
        <description>Adrenocorticotropic hormone level will be collected via blood draw. Change is defined as the difference in adrenocorticotropic hormone level from baseline to post emotional stress testing.</description>
        <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
        <population>This outcome was not assessed due to a lack of resources and a focus on other pertinent biomarkers per the literature.</population>
        <group_list>
          <group group_id="O1">
            <title>Vagal Nerve Stimulation</title>
            <description>Participants randomized to this arm will receive stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
GammaCore/electroCore non-invasive VNS device: Vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The intensity of the stimulus is adjusted by the user, to the maximum tolerable level to ensure VNS without causing excessive pain (typically 10-30 V). The duration of delivery is 2 minutes, one minute into which the high-resolution positron emission tomography (HR-PET) scan is conducted; following an additional 8 minutes, a second VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
          <group group_id="O2">
            <title>Sham Stimulation</title>
            <description>Participants randomized to this arm will receive sham stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
Sham gammaCore/electroCore: Sham vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The device is programmed such that no actual stimulation is given to the vagus nerve. The duration of delivery is 2 minutes, one minute into which the HR-PET scan is conducted; following an additional 8 minutes, a second sham VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . H2[15O] will be prepared on-site in the Emory PET Center cyclotron. During the hours of the test, an intravenous infusion of normal saline will be started to permit the bolus injection of H2[15O]. Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
        </group_list>
        <measure>
          <title>Level of Adrenocorticotropic Hormone</title>
          <description>Adrenocorticotropic hormone level will be collected via blood draw. Change is defined as the difference in adrenocorticotropic hormone level from baseline to post emotional stress testing.</description>
          <population>This outcome was not assessed due to a lack of resources and a focus on other pertinent biomarkers per the literature.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Level of Cortisol</title>
        <description>Cortisol level will be collected via blood draw. Change is defined as the difference in cortisol level from baseline to post emotional stress testing.</description>
        <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
        <population>This outcome was not assessed due to a lack of resources and a focus on other pertinent biomarkers per the literature.</population>
        <group_list>
          <group group_id="O1">
            <title>Vagal Nerve Stimulation</title>
            <description>Participants randomized to this arm will receive stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
GammaCore/electroCore non-invasive VNS device: Vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The intensity of the stimulus is adjusted by the user, to the maximum tolerable level to ensure VNS without causing excessive pain (typically 10-30 V). The duration of delivery is 2 minutes, one minute into which the high-resolution positron emission tomography (HR-PET) scan is conducted; following an additional 8 minutes, a second VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
          <group group_id="O2">
            <title>Sham Stimulation</title>
            <description>Participants randomized to this arm will receive sham stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
Sham gammaCore/electroCore: Sham vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The device is programmed such that no actual stimulation is given to the vagus nerve. The duration of delivery is 2 minutes, one minute into which the HR-PET scan is conducted; following an additional 8 minutes, a second sham VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . H2[15O] will be prepared on-site in the Emory PET Center cyclotron. During the hours of the test, an intravenous infusion of normal saline will be started to permit the bolus injection of H2[15O]. Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
        </group_list>
        <measure>
          <title>Level of Cortisol</title>
          <description>Cortisol level will be collected via blood draw. Change is defined as the difference in cortisol level from baseline to post emotional stress testing.</description>
          <population>This outcome was not assessed due to a lack of resources and a focus on other pertinent biomarkers per the literature.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Level of Epinephrine</title>
        <description>Epinephrine level will be collected via blood draw. Change is defined as the difference in epinephrine level from baseline to post emotional stress testing.</description>
        <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
        <population>This outcome was not assessed due to a lack of resources and a focus on other pertinent biomarkers per the literature.</population>
        <group_list>
          <group group_id="O1">
            <title>Vagal Nerve Stimulation</title>
            <description>Participants randomized to this arm will receive stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
GammaCore/electroCore non-invasive VNS device: Vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The intensity of the stimulus is adjusted by the user, to the maximum tolerable level to ensure VNS without causing excessive pain (typically 10-30 V). The duration of delivery is 2 minutes, one minute into which the high-resolution positron emission tomography (HR-PET) scan is conducted; following an additional 8 minutes, a second VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
          <group group_id="O2">
            <title>Sham Stimulation</title>
            <description>Participants randomized to this arm will receive sham stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
Sham gammaCore/electroCore: Sham vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The device is programmed such that no actual stimulation is given to the vagus nerve. The duration of delivery is 2 minutes, one minute into which the HR-PET scan is conducted; following an additional 8 minutes, a second sham VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . H2[15O] will be prepared on-site in the Emory PET Center cyclotron. During the hours of the test, an intravenous infusion of normal saline will be started to permit the bolus injection of H2[15O]. Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
        </group_list>
        <measure>
          <title>Level of Epinephrine</title>
          <description>Epinephrine level will be collected via blood draw. Change is defined as the difference in epinephrine level from baseline to post emotional stress testing.</description>
          <population>This outcome was not assessed due to a lack of resources and a focus on other pertinent biomarkers per the literature.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Level of Dopamine</title>
        <description>Dopamine level will be collected via blood draw. Change is defined as the difference in dopamine level from baseline to post emotional stress testing.</description>
        <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
        <population>This outcome was not assessed due to a lack of resources and a focus on other pertinent biomarkers per the literature.</population>
        <group_list>
          <group group_id="O1">
            <title>Vagal Nerve Stimulation</title>
            <description>Participants randomized to this arm will receive stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
GammaCore/electroCore non-invasive VNS device: Vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The intensity of the stimulus is adjusted by the user, to the maximum tolerable level to ensure VNS without causing excessive pain (typically 10-30 V). The duration of delivery is 2 minutes, one minute into which the high-resolution positron emission tomography (HR-PET) scan is conducted; following an additional 8 minutes, a second VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
          <group group_id="O2">
            <title>Sham Stimulation</title>
            <description>Participants randomized to this arm will receive sham stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
Sham gammaCore/electroCore: Sham vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The device is programmed such that no actual stimulation is given to the vagus nerve. The duration of delivery is 2 minutes, one minute into which the HR-PET scan is conducted; following an additional 8 minutes, a second sham VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . H2[15O] will be prepared on-site in the Emory PET Center cyclotron. During the hours of the test, an intravenous infusion of normal saline will be started to permit the bolus injection of H2[15O]. Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
        </group_list>
        <measure>
          <title>Level of Dopamine</title>
          <description>Dopamine level will be collected via blood draw. Change is defined as the difference in dopamine level from baseline to post emotional stress testing.</description>
          <population>This outcome was not assessed due to a lack of resources and a focus on other pertinent biomarkers per the literature.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Level of Norepinephrine</title>
        <description>Norepinephrine level will be collected via blood draw. Change is defined as the difference in norepinephrine level from baseline to post emotional stress testing.</description>
        <time_frame>Baseline, Post Stress Testing (Up to 4 Hours)</time_frame>
        <population>This outcome was not assessed due to a lack of resources and a focus on other pertinent biomarkers per the literature.</population>
        <group_list>
          <group group_id="O1">
            <title>Vagal Nerve Stimulation</title>
            <description>Participants randomized to this arm will receive stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
GammaCore/electroCore non-invasive VNS device: Vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The intensity of the stimulus is adjusted by the user, to the maximum tolerable level to ensure VNS without causing excessive pain (typically 10-30 V). The duration of delivery is 2 minutes, one minute into which the high-resolution positron emission tomography (HR-PET) scan is conducted; following an additional 8 minutes, a second VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
          <group group_id="O2">
            <title>Sham Stimulation</title>
            <description>Participants randomized to this arm will receive sham stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
Sham gammaCore/electroCore: Sham vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The device is programmed such that no actual stimulation is given to the vagus nerve. The duration of delivery is 2 minutes, one minute into which the HR-PET scan is conducted; following an additional 8 minutes, a second sham VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . H2[15O] will be prepared on-site in the Emory PET Center cyclotron. During the hours of the test, an intravenous infusion of normal saline will be started to permit the bolus injection of H2[15O]. Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
          </group>
        </group_list>
        <measure>
          <title>Level of Norepinephrine</title>
          <description>Norepinephrine level will be collected via blood draw. Change is defined as the difference in norepinephrine level from baseline to post emotional stress testing.</description>
          <population>This outcome was not assessed due to a lack of resources and a focus on other pertinent biomarkers per the literature.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From the time consent was given through all follow up (up to 4 hours post intervention).</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Vagal Nerve Stimulation</title>
          <description>Participants randomized to this arm will receive stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
GammaCore/electroCore non-invasive VNS device: Vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The intensity of the stimulus is adjusted by the user, to the maximum tolerable level to ensure VNS without causing excessive pain (typically 10-30 V). The duration of delivery is 2 minutes, one minute into which the high-resolution positron emission tomography (HR-PET) scan is conducted; following an additional 8 minutes, a second VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
        </group>
        <group group_id="E2">
          <title>Sham Stimulation</title>
          <description>Participants randomized to this arm will receive sham stimulation of the vagus nerve in conjunction with stress exposure.&#xD;
Sham gammaCore/electroCore: Sham vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The device is programmed such that no actual stimulation is given to the vagus nerve. The duration of delivery is 2 minutes, one minute into which the HR-PET scan is conducted; following an additional 8 minutes, a second sham VNS delivery is administered, after which another scan is obtained.&#xD;
O-15 water: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . H2[15O] will be prepared on-site in the Emory PET Center cyclotron. During the hours of the test, an intravenous infusion of normal saline will be started to permit the bolus injection of H2[15O]. Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Douglas Bremner</name_or_title>
      <organization>Emory University</organization>
      <phone>404-712-9569</phone>
      <email>doug.bremner@emory.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02992899
org study id: IRB00091171
nct id: NCT02992899
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: Yes
The tasks of the project are to map the potency and kinetics of the neurologic, autonomic
      peripheral, inflammatory, and behavioral responses to vagal nerve stimulation (VNS) vs. sham
      treatment, at baseline and in response to stressful traumatic scripts related to personal
      traumatic events, as well as a series of other stressors.
The purpose of this project is to develop the fundamental physiological understanding of
      feedback controlled vagal nerve stimulation (VNS) using positron emission tomography (PET)
      brain imaging and blood biomarker measurement with stress in healthy individuals and
      individuals with PTSD. Healthy human subjects with a history of psychological trauma but
      without the diagnosis of a psychiatric disorder (Phase 1), and human subjects with a history
      of PTSD (Phase 2), undergo PET imaging of the brain in conjunction with VNS or a sham
      treatment during exposure to neutral scripts and scripts of personal traumatic events. Blood
      is drawn simultaneously for measurement of a variety of stress responsive biomarkers,
      including inflammatory markers and neurohormones. A second PET scan with biomarkers assesses
      the delayed effects of VNS. On two other days subjects undergo exposure to random stressors
      with VNS or sham in conjunction with measurement of stress biomarkers.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: Single (Participant)
measure: Level of Interleukin-6 (IL6)
time frame: Baseline, Post Stress Testing (Up to 4 Hours)
description: IL6 level will be collected via blood draw. Change is defined as the difference in IL6 level from baseline to post emotional stress testing.
measure: Level of Tryptophan
time frame: Baseline, Post Stress Testing (Up to 4 Hours)
description: Tryptophan level will be collected via blood draw. Change is defined as the difference in tryptophan level from baseline to post emotional stress testing.
measure: Level of Kynurenine
time frame: Baseline, Post Stress Testing (Up to 4 Hours)
description: Kynurenine level will be collected via blood draw. Change is defined as the difference in kynurenine level from baseline to post emotional stress testing.
measure: Level of Kynurenic Acid
time frame: Baseline, Post Stress Testing (Up to 4 Hours)
description: Kynurenic acid level will be collected via blood draw. Change is defined as the difference in kynurenic acid level from baseline to post emotional stress testing.
measure: Level of 3-3 Hydroxykynurenine
time frame: Baseline, Post Stress Testing (Up to 4 Hours)
description: 3-3 hydroxykynurenine level will be collected via blood draw. Change is defined as the difference in 3-3 hydroxykynurenine level from baseline to post emotional stress testing.
measure: Level of Anthranilic Acid
time frame: Baseline, Post Stress Testing (Up to 4 Hours)
description: Anthranilic Acid level will be collected via blood draw. Change is defined as the difference in anthranilic acid level from baseline to post emotional stress testing.
measure: Level of Tumor Necrosis Factor (TNF)-Alpha
time frame: Baseline, Post Stress Testing (Up to 4 Hours)
description: TNF-alpha level will be collected via blood draw. Change is defined as the difference in TNF-alpha level from baseline to post emotional stress testing.
measure: Level of Interferon-Gamma
time frame: Baseline, Post Stress Testing (Up to 4 Hours)
description: Interferon-Gamma level will be collected via blood draw. Change is defined as the difference in Interferon-Gamma level from baseline to post emotional stress testing.
measure: Level of Interleukin-1 Beta
time frame: Baseline, Post Stress Testing (Up to 4 Hours)
description: Interleukin-1 Beta level will be collected via blood draw. Change is defined as the difference in Interleukin-1 Beta level from baseline to post emotional stress testing.
measure: Level of Interleukin-2 (IL2)
time frame: Baseline, Post Stress Testing (Up to 4 Hours)
description: IL2 level will be collected via blood draw. Change is defined as the difference in IL2 level from baseline to post emotional stress testing.
measure: Level of Interleukin-4 (IL4)
time frame: Baseline, Post Stress Testing (Up to 4 Hours)
description: IL4 level will be collected via blood draw. Change is defined as the difference in IL4 level from baseline to post emotional stress testing.
measure: Level of Interleukin-8 (IL8)
time frame: Baseline, Post Stress Testing (Up to 4 Hours)
description: IL8 level will be collected via blood draw. Change is defined as the difference in IL8 level from baseline to post emotional stress testing.
measure: Level of Interleukin-10 (IL10)
time frame: Baseline, Post Stress Testing (Up to 4 Hours)
description: IL10 level will be collected via blood draw. Change is defined as the difference in IL10 level from baseline to post emotional stress testing.
measure: Level of Interleukin-12p70 (IL12p70)
time frame: Baseline, Post Stress Testing (Up to 4 Hours)
description: IL12p70 level will be collected via blood draw. Change is defined as the difference in IL12p70 level from baseline to post emotional stress testing.
measure: Level of Interleukin-12p (IL12p)
time frame: Baseline, Post Stress Testing (Up to 4 Hours)
description: IL12p level will be collected via blood draw. Change is defined as the difference in IL12p level from baseline to post emotional stress testing.
measure: Level of Interleukin-13 (IL13)
time frame: Baseline, Post Stress Testing (Up to 4 Hours)
description: IL13 level will be collected via blood draw. Change is defined as the difference in IL13 level from baseline to post emotional stress testing.
measure: Level of Macrophage Migration Inhibitory Factor
time frame: Baseline, Post Stress Testing (Up to 4 Hours)
description: Macrophage migration inhibitory factor will be collected via blood draw. Change is defined as the difference in factor level from baseline to post emotional stress testing.
measure: Level of High-Mobility Group Protein B1
time frame: Baseline, Post Stress Testing (Up to 4 Hours)
description: High-mobility group protein B1 level will be collected via blood draw. Change is defined as the difference in high-mobility group protein B1 level from baseline to post emotional stress testing.
measure: Level of Adrenocorticotropic Hormone
time frame: Baseline, Post Stress Testing (Up to 4 Hours)
description: Adrenocorticotropic hormone level will be collected via blood draw. Change is defined as the difference in adrenocorticotropic hormone level from baseline to post emotional stress testing.
measure: Level of Cortisol
time frame: Baseline, Post Stress Testing (Up to 4 Hours)
description: Cortisol level will be collected via blood draw. Change is defined as the difference in cortisol level from baseline to post emotional stress testing.
measure: Level of Epinephrine
time frame: Baseline, Post Stress Testing (Up to 4 Hours)
description: Epinephrine level will be collected via blood draw. Change is defined as the difference in epinephrine level from baseline to post emotional stress testing.
measure: Level of Dopamine
time frame: Baseline, Post Stress Testing (Up to 4 Hours)
description: Dopamine level will be collected via blood draw. Change is defined as the difference in dopamine level from baseline to post emotional stress testing.
measure: Level of Norepinephrine
time frame: Baseline, Post Stress Testing (Up to 4 Hours)
description: Norepinephrine level will be collected via blood draw. Change is defined as the difference in norepinephrine level from baseline to post emotional stress testing.
arm group label: Vagal Nerve Stimulation
arm group type: Experimental
description: Participants randomized to this arm will receive stimulation of the vagus nerve in conjunction with stress exposure.
arm group label: Sham Stimulation
arm group type: Sham Comparator
description: Participants randomized to this arm will receive sham stimulation of the vagus nerve in conjunction with stress exposure.
intervention type: Device
intervention name: GammaCore/electroCore non-invasive VNS device
description: Vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The intensity of the stimulus (the current amplitude) is adjusted by the user, to the maximum tolerable level to ensure VNS without causing excessive pain (typically 10-30 V), the burst frequency to 5 kilohertz (kHz), and the envelope frequency to 25 Hz. These are the standard frequency settings that electroCore has demonstrated to be most effective in capturing the vagus nerve based on evoked potential studies. The duration of delivery is 2 minutes, one minute into which the high-resolution positron emission tomography (HR-PET) scan is conducted; following an additional 8 minutes, a second VNS delivery is administered, after which another scan is obtained.
arm group label: Vagal Nerve Stimulation
intervention type: Device
intervention name: Sham gammaCore/electroCore
description: Sham vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The device is programmed such that no actual stimulation is given to the vagus nerve. The duration of delivery is 2 minutes, one minute into which the HR-PET scan is conducted; following an additional 8 minutes, a second sham VNS delivery is administered, after which another scan is obtained.
arm group label: Sham Stimulation
intervention type: Drug
intervention name: O-15 water
description: Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . H2[15O] will be prepared on-site in the Emory PET Center cyclotron. During the hours of the test, an intravenous infusion of normal saline will be started to permit the bolus injection of H2[15O]. Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.
arm group label: Sham Stimulation
arm group label: Vagal Nerve Stimulation
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: James D Bremner, MD
role: Principal Investigator
affiliation: Emory University
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Emory University
investigator full name: J. Douglas Bremner, MD
investigator title: Professor
mesh term: Stress Disorders, Traumatic
mesh term: Stress Disorders, Post-Traumatic
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 