<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/NCT03778307</url>
  </required_header>
  <id_info>
    <org_study_id>AAAR8563</org_study_id>
    <secondary_id>R01HL139614</secondary_id>
    <nct_id>NCT03778307</nct_id>
  </id_info>
  <brief_title>Key Dimensions of PTSD and ED</brief_title>
  <official_title>Key Dimensions of Post-traumatic Stress Disorder (PTSD) and Endothelial Dysfunction (ED)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, Los Angeles</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, Los Angeles</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will test whether endothelial dysfunction could be the early subclinical mechanism&#xD;
      by which posttraumatic stress disorder (PTSD) increases cardiovascular disease (CVD) risk,&#xD;
      and whether posttraumatic fear-a key component of PTSD-or another PTSD dimension could be the&#xD;
      target to offset that risk. The results of this study may help trauma-exposed individuals who&#xD;
      are at risk of having CVD events.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Posttraumatic stress disorder (PTSD) increases risk of incident cardiovascular disease (CVD)&#xD;
      by 25-50%. Most individuals (50-90%) experience a traumatic event in their lifetime, and PTSD&#xD;
      is the fifth most common psychiatric disorder. Experts have now called for increased CVD&#xD;
      surveillance after trauma and for PTSD treatment trials powered to reduce CVD risk. However,&#xD;
      both CVD risk and PTSD are complex phenomena that likely interact in nuanced ways. This study&#xD;
      will determine which PTSD dimension(s) contribute to endothelial dysfunction, one of the&#xD;
      earliest modifiable precursors to CVD. The investigators will examine cross-sectional and&#xD;
      longitudinal associations of PTSD and its underlying dimensions with functional and,&#xD;
      secondarily, cellular measures of endothelial dysfunction (FMD and circulating endothelial&#xD;
      cell-derived microparticles, respectively) in a community-dwelling sample of CVD-free adult&#xD;
      men and women with a history of trauma (50% with current PTSD).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 20, 2019</start_date>
  <completion_date type="Anticipated">June 30, 2025</completion_date>
  <primary_completion_date type="Anticipated">September 30, 2023</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Flow-mediated dilation of the brachial artery (FMD) %</measure>
    <time_frame>Baseline</time_frame>
    <description>FMD is the percent difference in diameter of the brachial artery, before and after occlusion. Impaired endothelial function occurs when blood vessels are unable to dilate fully in response to nitric oxide synthesis and release, which is manifested as impaired endothelium-dependent vasodilation (i.e., lower FMD). Lower FMD has been associated with the degree of coronary atherosclerosis and predicts CVD events.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Circulating EMPs expressing CD62E</measure>
    <time_frame>Baseline</time_frame>
    <description>EMPs expressing CD62E (i.e., endothelial cell activation) and CD31 (i.e., endothelial cell apoptosis) will be measured. Assessments of circulating EMPs will be measured using flow cytometry, and total flow cytometry counts will be converted to the number of EMPs per uL of blood. Higher concentrations of EMPs expressing CD62E and CD31 indicate greater endothelial dysfunction.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Circulating EMPs expressing CD31</measure>
    <time_frame>Baseline</time_frame>
    <description>EMPs expressing CD62E (i.e., endothelial cell activation) and CD31 (i.e., endothelial cell apoptosis) will be measured. Assessments of circulating EMPs will be measured using flow cytometry, and total flow cytometry counts will be converted to the number of EMPs per uL of blood. Higher concentrations of EMPs expressing CD62E and CD31 indicate greater endothelial dysfunction.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Trauma</condition>
  <condition>PTSD</condition>
  <condition>Endothelial Dysfunction</condition>
  <arm_group>
    <arm_group_label>Trauma exposed without PTSD</arm_group_label>
    <description>Individuals with a history of trauma exposure who do not have current PTSD</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Trauma exposed with PTSD</arm_group_label>
    <description>Individuals with a history of trauma exposure and a current diagnosis of PTSD</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Psychophysiological fear conditioning and extinction task</intervention_name>
    <description>Behavioral task to assess psychophysiological measures of fear</description>
    <arm_group_label>Trauma exposed with PTSD</arm_group_label>
    <arm_group_label>Trauma exposed without PTSD</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Eyetracking task</intervention_name>
    <description>Behavioral task to assess dysphoria-relevant attention allocation</description>
    <arm_group_label>Trauma exposed with PTSD</arm_group_label>
    <arm_group_label>Trauma exposed without PTSD</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood and urine samples for inflammatory and oxidative stress biomarkers; a blood sample for&#xD;
      DNA collection is an optional aspect of this study&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Trauma-exposed adults without a history of cardiovascular disease recruited from the&#xD;
        community&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Aged 18+ years&#xD;
&#xD;
          -  History of exposure to a psychological trauma (e.g., natural disaster, physical&#xD;
             assault)&#xD;
&#xD;
          -  Fluent in English&#xD;
&#xD;
          -  Willing to and capable of providing informed consent&#xD;
&#xD;
        Additional Inclusion Criteria for the PTSD Group&#xD;
&#xD;
          -  Diagnosed with current PTSD (duration of at least 1 month) using the&#xD;
             Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual 5th Edition&#xD;
             (DSM-5) (CAPS-5) at the diagnostic interview assessment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of CVD (i.e., diagnosis of myocardial infarction, unstable angina, heart&#xD;
             failure, peripheral artery disease, or stroke)&#xD;
&#xD;
          -  Deemed unable to comply with the protocol (either self-selected or by indicating&#xD;
             during screening that could not complete all requested tasks)&#xD;
&#xD;
          -  Current bipolar disorder or psychotic disorder&#xD;
&#xD;
          -  Mild or more severe cognitive impairment [Mini-Mental State Exam (MMSE)3 score ≤18]&#xD;
&#xD;
          -  Current moderate or severe substance use disorder&#xD;
&#xD;
          -  Acute, unstable, or severe medical disorder or pregnancy&#xD;
&#xD;
          -  Deemed to need immediate psychiatric intervention (e.g., active suicidality)&#xD;
&#xD;
          -  Use of antipsychotic, mood stabilizer, antidepressant, or stimulant medication in the&#xD;
             past 4 weeks&#xD;
&#xD;
          -  Daily benzodiazepine use in the past 2 weeks&#xD;
&#xD;
        Additional Exclusion Criteria for the Trauma-Exposed Matched Control Group&#xD;
&#xD;
          -  Current or past diagnosis of any DSM-5 psychiatric disorder&#xD;
&#xD;
          -  CAPS-5 total score ≥25&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jennifer A Sumner, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, Los Angeles</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Shiloh Cleveland, BA</last_name>
    <phone>(310) 737-8279</phone>
    <email>scleveland@psych.ucla.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>UCLA</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Shiloh Cleveland, BA</last_name>
      <email>scleveland@psych.ucla.edu</email>
    </contact>
    <contact_backup>
      <last_name>Jennifer A Sumner, PhD</last_name>
      <phone>(310) 794-9860</phone>
      <email>jsumner@psych.ucla.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Jennifer A Sumner, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>December 7, 2018</study_first_submitted>
  <study_first_submitted_qc>December 14, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 19, 2018</study_first_posted>
  <last_update_submitted>May 2, 2023</last_update_submitted>
  <last_update_submitted_qc>May 2, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of California, Los Angeles</investigator_affiliation>
    <investigator_full_name>Jennifer A. Sumner, PhD</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>Trauma</keyword>
  <keyword>PTSD</keyword>
  <keyword>Endothelial Dysfunction</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stress Disorders, Post-Traumatic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03778307
org study id: AAAR8563
secondary id: R01HL139614
nct id: NCT03778307
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study will test whether endothelial dysfunction could be the early subclinical mechanism
      by which posttraumatic stress disorder (PTSD) increases cardiovascular disease (CVD) risk,
      and whether posttraumatic fear-a key component of PTSD-or another PTSD dimension could be the
      target to offset that risk. The results of this study may help trauma-exposed individuals who
      are at risk of having CVD events.
Posttraumatic stress disorder (PTSD) increases risk of incident cardiovascular disease (CVD)
      by 25-50%. Most individuals (50-90%) experience a traumatic event in their lifetime, and PTSD
      is the fifth most common psychiatric disorder. Experts have now called for increased CVD
      surveillance after trauma and for PTSD treatment trials powered to reduce CVD risk. However,
      both CVD risk and PTSD are complex phenomena that likely interact in nuanced ways. This study
      will determine which PTSD dimension(s) contribute to endothelial dysfunction, one of the
      earliest modifiable precursors to CVD. The investigators will examine cross-sectional and
      longitudinal associations of PTSD and its underlying dimensions with functional and,
      secondarily, cellular measures of endothelial dysfunction (FMD and circulating endothelial
      cell-derived microparticles, respectively) in a community-dwelling sample of CVD-free adult
      men and women with a history of trauma (50% with current PTSD).
observational model: Case-Control
time perspective: Cross-Sectional
measure: Flow-mediated dilation of the brachial artery (FMD) %
time frame: Baseline
description: FMD is the percent difference in diameter of the brachial artery, before and after occlusion. Impaired endothelial function occurs when blood vessels are unable to dilate fully in response to nitric oxide synthesis and release, which is manifested as impaired endothelium-dependent vasodilation (i.e., lower FMD). Lower FMD has been associated with the degree of coronary atherosclerosis and predicts CVD events.
measure: Circulating EMPs expressing CD62E
time frame: Baseline
description: EMPs expressing CD62E (i.e., endothelial cell activation) and CD31 (i.e., endothelial cell apoptosis) will be measured. Assessments of circulating EMPs will be measured using flow cytometry, and total flow cytometry counts will be converted to the number of EMPs per uL of blood. Higher concentrations of EMPs expressing CD62E and CD31 indicate greater endothelial dysfunction.
measure: Circulating EMPs expressing CD31
time frame: Baseline
description: EMPs expressing CD62E (i.e., endothelial cell activation) and CD31 (i.e., endothelial cell apoptosis) will be measured. Assessments of circulating EMPs will be measured using flow cytometry, and total flow cytometry counts will be converted to the number of EMPs per uL of blood. Higher concentrations of EMPs expressing CD62E and CD31 indicate greater endothelial dysfunction.
arm group label: Trauma exposed without PTSD
description: Individuals with a history of trauma exposure who do not have current PTSD
arm group label: Trauma exposed with PTSD
description: Individuals with a history of trauma exposure and a current diagnosis of PTSD
intervention type: Behavioral
intervention name: Psychophysiological fear conditioning and extinction task
description: Behavioral task to assess psychophysiological measures of fear
arm group label: Trauma exposed with PTSD
arm group label: Trauma exposed without PTSD
intervention type: Behavioral
intervention name: Eyetracking task
description: Behavioral task to assess dysphoria-relevant attention allocation
arm group label: Trauma exposed with PTSD
arm group label: Trauma exposed without PTSD
Blood and urine samples for inflammatory and oxidative stress biomarkers; a blood sample for
      DNA collection is an optional aspect of this study
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jennifer A Sumner, PhD
role: Principal Investigator
affiliation: University of California, Los Angeles
last name: Shiloh Cleveland, BA
phone: (310) 737-8279
email: scleveland@psych.ucla.edu
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of California, Los Angeles
investigator full name: Jennifer A. Sumner, PhD
investigator title: Assistant Professor
mesh term: Stress Disorders, Post-Traumatic
sharing ipd: No