<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/NCT02256644</url>
  </required_header>
  <id_info>
    <org_study_id>575B</org_study_id>
    <nct_id>NCT02256644</nct_id>
  </id_info>
  <brief_title>Genomics of Posttraumatic Stress Disorder in Veterans</brief_title>
  <official_title>CSP #575B - Genomics of Posttraumatic Stress Disorder Among Veterans</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>VA Office of Research and Development</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>VA Office of Research and Development</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Posttraumatic Stress Disorder (PTSD), as a common and serious mental health condition,&#xD;
      affects about 25% of all military personnel that have served in combat. People suffering from&#xD;
      PTSD may experience traumatic flashbacks, trouble sleeping, and problems in their&#xD;
      relationships. This study is intended to help identify genes that influence and increase the&#xD;
      risk of PTSD, to improve ways of detecting and treating the condition in the future.&#xD;
&#xD;
      Previous research has studied genes that increase the risk of PTSD, but none of these have&#xD;
      included a Veteran-only population. The current study focuses on US Veterans, utilizing the&#xD;
      VA Million Veteran Program (MVP) database of approximately 300,000 participants as of August&#xD;
      2014. In this context, participants with PTSD are referred to as &quot;cases&quot; and Veterans without&#xD;
      PTSD are referred to as &quot;controls.&quot;&#xD;
&#xD;
      This project will be done in three stages. The first stage will look at MVP-obtained data and&#xD;
      electronic health record (EHR) data to implement methods for identifying combat-exposed case&#xD;
      patients with PTSD and combat-exposed control patients without PTSD. The second stage will&#xD;
      assemble and validate a study population of 20,000 participants &quot;including 10,000&#xD;
      combat-exposed Veterans with PTSD as cases and 10,000 combat-exposed Veterans without PTSD as&#xD;
      controls. The third stage will conduct genetic analyses (&quot;genotyping&quot;) comparing the cases to&#xD;
      controls, to identify genes associated with increased risk of developing the condition.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background and Objectives&#xD;
&#xD;
      Posttraumatic stress disorder (PTSD) is a severe, sometimes disabling, anxiety disorder that&#xD;
      can develop after a potentially traumatic event involving actual or threatened death, serious&#xD;
      injury, or sexual violation. The diagnosis of PTSD requires symptoms for at least one month&#xD;
      from three categories: re-experiencing, avoidance, and increased arousal. In contrast to an&#xD;
      acute response to trauma, the stress reactions of persons who develop PTSD do not resolve&#xD;
      quickly; symptoms can last for long periods of time and may increase in severity.&#xD;
&#xD;
      The rate of PTSD (and consequent disability) is especially high among combat-exposed military&#xD;
      Veterans. Studies of Vietnam combat veterans have consistently found a lifetime PTSD&#xD;
      prevalence of 25-30% of men, although rates of persistent/chronic PTSD have been somewhat&#xD;
      lower (15-20%). Studies of OEF/OIF Army personnel have reported rates of PTSD in the 10% to&#xD;
      15% range following deployment (Thomas et al 2010). These rates are much higher than the rate&#xD;
      of PTSD in the general US population, estimated to be about 6.8% (Kessler et al 2005).&#xD;
&#xD;
      PTSD has been shown to be influenced genetically, and previous work has identified several&#xD;
      possible genes that increase the risk of PTSD. Although several genomewide association&#xD;
      studies (GWASs) have been conducted, the corresponding statistical power has been modest, and&#xD;
      none included a Veteran-only population. The proposed study will address those deficiencies&#xD;
      by conducting a well-powered case-control GWAS study in a large sample of US Veterans with&#xD;
      PTSD as &quot;cases&quot; and psychiatrically-healthy Veterans as &quot;controls.&quot;&#xD;
&#xD;
      Preliminary Data and Research Design&#xD;
&#xD;
      The study will use a case-control design nested within the VA Million Veteran Program (MVP),&#xD;
      with genotype as the exposure variable and PTSD diagnosis (yes/no) as the outcome variable.&#xD;
      The pool of potential PTSD cases will be identified initially based on self-report of a PTSD&#xD;
      diagnosis on a previously completed self-report questionnaire collected in MVP, or evidence&#xD;
      of a PTSD diagnosis in the VA electronic health record (EHR). Specific validation procedures&#xD;
      will narrow the pool to confirmed PTSD cases and controls. Based on available MVP and VA EHR&#xD;
      data, the investigators estimate a currently available source population of more than 11,000&#xD;
      confirmed PTSD cases among the approximately 145,000 MVP enrollees to date. By the time this&#xD;
      project gets underway, the number of available cases (and controls) will be even higher, due&#xD;
      to ongoing enrollment into MVP.&#xD;
&#xD;
      Laboratory Methods and Statistical Analyses&#xD;
&#xD;
      This PTSD GWAS will compare 10,000 combat-exposed Veterans with PTSD to 10,000 combat-exposed&#xD;
      controls. A to-be-selected microarray (see narrative) will be employed that contains&#xD;
      approximately 245K genomewide association markers, 250K exonic markers and INDELs, 70K novel&#xD;
      loss-of-function SNPs and INDELs, and 115K &quot;custom&quot; markers. Genotypes will be imputed to&#xD;
      approximately 1KG for statistical analysis, and up to 50 putatively-associated SNPs that are&#xD;
      initially imputed will be genotyped directly in the same sample.&#xD;
&#xD;
      Anticipated Results and Relevance&#xD;
&#xD;
      Genetic loci affecting combat-related PTSD risk and resilience will be identified, providing&#xD;
      important information to inform therapeutic targets related to prevention and treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">December 1, 2013</start_date>
  <completion_date type="Anticipated">September 30, 2023</completion_date>
  <primary_completion_date type="Actual">August 1, 2014</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>Other</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>PTSD diagnosis</measure>
    <time_frame>2 years</time_frame>
    <description>The study will use a case-control design nested within the VA Million Veteran Program (MVP), with genotype as the exposure variable and PTSD diagnosis (yes/no) as the outcome variable.</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">20000</enrollment>
  <condition>PTSD</condition>
  <arm_group>
    <arm_group_label>Million Veteran Program (MVP) participants</arm_group_label>
    <description>Veterans who are currently enrolled in the Million Veteran Program.</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Affymetrix Axiom Biobank chip, with technical specifications including &quot;295K tag SNPs&quot;, &quot;260K&#xD;
      exomic content&quot;, &quot;65K loss-of-function SNPs &amp; INDELs&quot;, &quot;25K psych content&quot;, and &quot;23K eQTL&#xD;
      markers&quot;.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        The investigators expect 70-80% European-American (EA) and 20-30% African American (AA) in&#xD;
        the current study&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Combat-exposed Veterans who participated in the Million Veteran Program.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  schizophrenia&#xD;
&#xD;
          -  bipolar disorder&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Murray B Stein, MD MPH</last_name>
    <role>Study Chair</role>
    <affiliation>VA San Diego Healthcare System, San Diego, CA</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Joel Gelernter, MD</last_name>
    <role>Study Chair</role>
    <affiliation>VA Connecticut Healthcare System West Haven Campus, West Haven, CT</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>VA San Diego Healthcare System, San Diego, CA</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92161-0002</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.research.va.gov/programs/csp/csp575B.cfm</url>
    <description>Related Info</description>
  </link>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>October 1, 2014</study_first_submitted>
  <study_first_submitted_qc>October 1, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 3, 2014</study_first_posted>
  <last_update_submitted>August 23, 2023</last_update_submitted>
  <last_update_submitted_qc>August 23, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 24, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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/NCT02256644
org study id: 575B
nct id: NCT02256644
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Posttraumatic Stress Disorder (PTSD), as a common and serious mental health condition,
      affects about 25% of all military personnel that have served in combat. People suffering from
      PTSD may experience traumatic flashbacks, trouble sleeping, and problems in their
      relationships. This study is intended to help identify genes that influence and increase the
      risk of PTSD, to improve ways of detecting and treating the condition in the future.

      Previous research has studied genes that increase the risk of PTSD, but none of these have
      included a Veteran-only population. The current study focuses on US Veterans, utilizing the
      VA Million Veteran Program (MVP) database of approximately 300,000 participants as of August
      2014. In this context, participants with PTSD are referred to as "cases" and Veterans without
      PTSD are referred to as "controls."

      This project will be done in three stages. The first stage will look at MVP-obtained data and
      electronic health record (EHR) data to implement methods for identifying combat-exposed case
      patients with PTSD and combat-exposed control patients without PTSD. The second stage will
      assemble and validate a study population of 20,000 participants "including 10,000
      combat-exposed Veterans with PTSD as cases and 10,000 combat-exposed Veterans without PTSD as
      controls. The third stage will conduct genetic analyses ("genotyping") comparing the cases to
      controls, to identify genes associated with increased risk of developing the condition.
Background and Objectives

      Posttraumatic stress disorder (PTSD) is a severe, sometimes disabling, anxiety disorder that
      can develop after a potentially traumatic event involving actual or threatened death, serious
      injury, or sexual violation. The diagnosis of PTSD requires symptoms for at least one month
      from three categories: re-experiencing, avoidance, and increased arousal. In contrast to an
      acute response to trauma, the stress reactions of persons who develop PTSD do not resolve
      quickly; symptoms can last for long periods of time and may increase in severity.

      The rate of PTSD (and consequent disability) is especially high among combat-exposed military
      Veterans. Studies of Vietnam combat veterans have consistently found a lifetime PTSD
      prevalence of 25-30% of men, although rates of persistent/chronic PTSD have been somewhat
      lower (15-20%). Studies of OEF/OIF Army personnel have reported rates of PTSD in the 10% to
      15% range following deployment (Thomas et al 2010). These rates are much higher than the rate
      of PTSD in the general US population, estimated to be about 6.8% (Kessler et al 2005).

      PTSD has been shown to be influenced genetically, and previous work has identified several
      possible genes that increase the risk of PTSD. Although several genomewide association
      studies (GWASs) have been conducted, the corresponding statistical power has been modest, and
      none included a Veteran-only population. The proposed study will address those deficiencies
      by conducting a well-powered case-control GWAS study in a large sample of US Veterans with
      PTSD as "cases" and psychiatrically-healthy Veterans as "controls."

      Preliminary Data and Research Design

      The study will use a case-control design nested within the VA Million Veteran Program (MVP),
      with genotype as the exposure variable and PTSD diagnosis (yes/no) as the outcome variable.
      The pool of potential PTSD cases will be identified initially based on self-report of a PTSD
      diagnosis on a previously completed self-report questionnaire collected in MVP, or evidence
      of a PTSD diagnosis in the VA electronic health record (EHR). Specific validation procedures
      will narrow the pool to confirmed PTSD cases and controls. Based on available MVP and VA EHR
      data, the investigators estimate a currently available source population of more than 11,000
      confirmed PTSD cases among the approximately 145,000 MVP enrollees to date. By the time this
      project gets underway, the number of available cases (and controls) will be even higher, due
      to ongoing enrollment into MVP.

      Laboratory Methods and Statistical Analyses

      This PTSD GWAS will compare 10,000 combat-exposed Veterans with PTSD to 10,000 combat-exposed
      controls. A to-be-selected microarray (see narrative) will be employed that contains
      approximately 245K genomewide association markers, 250K exonic markers and INDELs, 70K novel
      loss-of-function SNPs and INDELs, and 115K "custom" markers. Genotypes will be imputed to
      approximately 1KG for statistical analysis, and up to 50 putatively-associated SNPs that are
      initially imputed will be genotyped directly in the same sample.

      Anticipated Results and Relevance

      Genetic loci affecting combat-related PTSD risk and resilience will be identified, providing
      important information to inform therapeutic targets related to prevention and treatment.
observational model: Case-Control
time perspective: Other
measure: PTSD diagnosis
time frame: 2 years
description: The study will use a case-control design nested within the VA Million Veteran Program (MVP), with genotype as the exposure variable and PTSD diagnosis (yes/no) as the outcome variable.
arm group label: Million Veteran Program (MVP) participants
description: Veterans who are currently enrolled in the Million Veteran Program.
Affymetrix Axiom Biobank chip, with technical specifications including "295K tag SNPs", "260K
      exomic content", "65K loss-of-function SNPs & INDELs", "25K psych content", and "23K eQTL
      markers".
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Murray B Stein, MD MPH
role: Study Chair
affiliation: VA San Diego Healthcare System, San Diego, CA
last name: Joel Gelernter, MD
role: Study Chair
affiliation: VA Connecticut Healthcare System West Haven Campus, West Haven, CT
facility: 
country: United States
url: http://www.research.va.gov/programs/csp/csp575B.cfm
description: Related Info
responsible party type: Sponsor
mesh term: Stress Disorders, Post-Traumatic
sharing ipd: No