<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/NCT01687153</url>
  </required_header>
  <id_info>
    <org_study_id>ADC-044</org_study_id>
    <secondary_id>W81XWH-12-2-0012</secondary_id>
    <secondary_id>W81XWH-13-1-0259</secondary_id>
    <secondary_id>W81XWH-14-1-0462</secondary_id>
    <nct_id>NCT01687153</nct_id>
  </id_info>
  <brief_title>A Study of Brain Aging in Vietnam War Veterans</brief_title>
  <acronym>DOD-ADNI</acronym>
  <official_title>Effects of Traumatic Brain Injury and Post Traumatic Stress Disorder on Alzheimer's Disease (AD) in Veterans Using Alzheimer's Disease Neuroimaging Initiative (ADNI)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Southern California</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>United States Department of Defense</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
    <collaborator>
      <agency>Telemedicine &amp; Advanced Technology Research Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Northern California Institute of Research and Education</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>San Francisco Veterans Affairs Medical Center</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
    <collaborator>
      <agency>Alzheimer's Therapeutic Research Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Southern California</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Traumatic brain injury (TBI) and post traumatic stress disorder (PTSD) are common combat&#xD;
      related problems and may be associated with a greater risk of Alzheimer's disease (AD). The&#xD;
      purpose of this study is to examine the possible connections between TBI and PTSD, and the&#xD;
      signs and symptoms of AD on Veterans as they age.&#xD;
&#xD;
      The information collected will help to learn more about how these injuries may affect&#xD;
      Veterans of the Vietnam War as they grow older, as well as Veterans of the current wars in&#xD;
      Iraq and Afghanistan, who also have these types of combat related injuries.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The overall long-term goal of this project is to prevent AD, which affects almost 50% of the&#xD;
      US population over 85 years of age, and is the most common cause of dementia. Clinical signs&#xD;
      and symptoms of AD include cognitive impairments, especially memory and emotional&#xD;
      disturbances. In order to accomplish this goal of prevention, a population at risk must be&#xD;
      identified. Evidence suggests that both TBI and PTSD increase risk for cognitive decline, AD,&#xD;
      and dementia.&#xD;
&#xD;
      TBI and PTSD are common problems resulting from military service. Thus far, there have been&#xD;
      no prospective studies using imaging and biomarkers, which directly measure changes in the&#xD;
      brain and AD pathology to study the effects of TBI and PTSD. This proposed study will provide&#xD;
      novel data to test these hypotheses. The results will have major implications for&#xD;
      identifying, subjects at increased risk for AD, a possible need for early detection of AD in&#xD;
      military Veterans with histories of TBI and PTSD, and a possible need to employ prevention&#xD;
      and treatment measures to avoid accelerated development of AD in US military Veterans. This&#xD;
      study is a first step toward a larger, more comprehensive study of dementia risk factors in&#xD;
      Veterans. The results will lead to a design and statistical powering of a prevention trial.&#xD;
      Therefore, this project could be the first step toward the prevention of AD in Veterans, and&#xD;
      in the general population.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">September 21, 2021</completion_date>
  <primary_completion_date type="Actual">September 21, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Rates of change in brain regions based on neuroimaging</measure>
    <time_frame>1 year</time_frame>
    <description>Rates of change in brain regions based on neuroimaging (magnetic resonance imaging [MRI] and amyloid positron-emission tomography [PET]) to show that those with TBI and/or PTSD have increased evidence for AD compared to Veteran controls</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Rates of change in CSF amyloid beta and CSF tau/P tau levels based on biomarkers</measure>
    <time_frame>1 year</time_frame>
    <description>Rates of change in CSF amyloid beta and CSF tau/P tau levels based on biomarkers such as cerebrospinal fluid (CSF) to show that those with TBI and/or PTSD have increased evidence for AD compared to Veteran controls</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Rates of change in neuropsychological measures of memory and general cognitive performance</measure>
    <time_frame>1 Year</time_frame>
    <description>Rates of change in neuropsychological measures of memory and general cognitive performance based on cognitive measures to show that those with TBI and/or PTSD have increased evidence for AD compared to Veteran controls</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Correlations within each group (TBI and PTSD) to assess whether baseline levels or rates of atrophy or cognitive decline are associated with severity of TBI or PTSD</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Group differences in the patterns of amyloid deposition (from Florbetapir F 18) and brain atrophy</measure>
    <time_frame>1 year</time_frame>
    <description>Group differences may give insight into whether TBI or PTSD is associated with reduced brain reserve causing greater cognitive impairments as indicated by neuropsychological test performance.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Group differences in white matter integrity as assessed with Diffusion Tension Imaging (DTI)</measure>
    <time_frame>1 year</time_frame>
    <description>Group differences in axonal damage as indicated by white matter integrity measured with DTI to determine if axonal injury resulting from TBI is associated with greater amyloid accumulation or whether brain regions with axonal damage have less amyloid accumulation due to disconnection and reduced brain activity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of change of tau deposition as measured by 18F-AV-1451</measure>
    <time_frame>1 year</time_frame>
    <description>Rates of change in brain regions based on Tau PET neuroimaging to show that those with TBI and/or PTSD have increased evidence for AD compared to Veteran controls</description>
  </secondary_outcome>
  <number_of_groups>6</number_of_groups>
  <enrollment type="Actual">289</enrollment>
  <condition>Traumatic Brain Injury</condition>
  <condition>Post Traumatic Stress Disorder</condition>
  <condition>Alzheimer's Disease</condition>
  <condition>Mild Cognitive Impairment</condition>
  <arm_group>
    <arm_group_label>Traumatic Brain Injury (TBI)</arm_group_label>
    <description>65-100 Vietnam Veterans with Traumatic Brain Injury (TBI), but without PTSD, mild cognitive impairment (MCI)/dementia</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Post Traumatic Stress Disorder (PTSD)</arm_group_label>
    <description>65-100 Vietnam Veterans with PTSD, but without TBI, MCI/dementia</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Controls</arm_group_label>
    <description>65-100 Vietnam Veteran Controls without TBI or PTSD and comparable in age, gender, and education to the other cohorts</description>
  </arm_group>
  <arm_group>
    <arm_group_label>TBI w/ MCI</arm_group_label>
    <description>65-100 Vietnam Veterans with TBI but without PTSD who meet the criteria for MCI but not dementia</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PTSD w/ MCI</arm_group_label>
    <description>65-100 Vietnam Veterans with PTSD but without TBI who meet the criteria for MCI but not dementia</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Controls w/ MCI</arm_group_label>
    <description>65-100 Vietnam Veteran Controls without TBI or PTSD who meet the criteria for MCI but not dementia, and are comparable in age, gender, and education to the other cohorts</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      blood, urine, cerobrospinal fluid&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Vietnam Veterans&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Participants will be classified as either controls, TBI, or PTSD. General&#xD;
        Inclusion/Exclusion Criteria will apply to all groups, with specific criteria for each&#xD;
        group as described below.&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
        General (applies to each cohort):&#xD;
&#xD;
          -  Subjects must be Veterans of the Vietnam War, 50-90 years of age. (Subjects 60-80&#xD;
             years of age will be selected first, while subjects &lt;60 or &gt;80 years of age will be&#xD;
             added if recruitment numbers are too low in the 60-80 age range);&#xD;
&#xD;
          -  Must live within 150 miles of the closest ADNI clinic in subject's area.&#xD;
&#xD;
        Specific Inclusion Criteria for Controls:&#xD;
&#xD;
          -  Comparable in age, gender, and education with TBI and PTSD groups;&#xD;
&#xD;
          -  May be receiving Veterans Affairs (VA) disability payments for something other than&#xD;
             TBI or PTSD - or no disability at all.&#xD;
&#xD;
        Specific Inclusion Criteria for TBI:&#xD;
&#xD;
          -  Subjects must have a documented history of moderate-severe non-penetrating TBI, which&#xD;
             occurred during military service in Vietnam (identified from the Department of Defense&#xD;
             or VA records);&#xD;
&#xD;
          -  TBI will be defined as:&#xD;
&#xD;
               -  Loss of consciousness,&#xD;
&#xD;
               -  Post-traumatic amnesia &gt;24 hours, OR&#xD;
&#xD;
               -  Alteration of consciousness or mental state &gt;24 hours&#xD;
&#xD;
        Specific Inclusion Criteria for PTSD:&#xD;
&#xD;
          -  Subjects who meet the Structured Clinical Interview 1 of the Diagnositic and&#xD;
             Statistical Manual of Mental Disorders, Version IV, (Axis 1) - Text Revision [SCID-I&#xD;
             of the DSM-IV-TR] criteria for current/chronic PTSD (identified by records, and&#xD;
             verified by our telephone assessments);&#xD;
&#xD;
          -  In addition to meeting DSM-IV-TR criteria for current/chronic PTSD, subjects must have&#xD;
             a minimum current Clinician Administered PTSD Scale (CAPS) score of 50 as determined&#xD;
             by telephone assessment;&#xD;
&#xD;
          -  The PTSD symptoms contributing to the PTSD Diagnosis and Current CAPS score must be&#xD;
             related to a Vietnam War related trauma.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        General (applies to each cohort):&#xD;
&#xD;
          -  MCI/dementia;&#xD;
&#xD;
          -  History of psychosis or bipolar affective disorder;&#xD;
&#xD;
          -  History of alcohol or substance abuse/dependence within the past 5 years (by DSM-IV-TR&#xD;
             criteria) or a prior prolonged history of abuse;&#xD;
&#xD;
          -  MRI-related exclusions: aneurysm clips, metal implants that are determined to be&#xD;
             unsafe for MRI; and/or claustrophobia;&#xD;
&#xD;
          -  Contraindications for lumbar puncture, PET scan, or other procedures in this study;&#xD;
&#xD;
          -  Any major medical condition must be stable for at least 4 months prior to enrollment.&#xD;
             These include but are not limited to clinically significant hepatic, renal, pulmonary,&#xD;
             metabolic or endocrine disease, cancer, HIV infection and AIDS, as well as&#xD;
             cardiovascular disease, including:&#xD;
&#xD;
               -  cardiac surgery or myocardial infarction within the last 4 weeks;&#xD;
&#xD;
               -  unstable angina;&#xD;
&#xD;
               -  acute decompensated congestive heart failure or class IV heart failures;&#xD;
&#xD;
               -  current significant cardiac arrhythmia or conduction disturbance particularly&#xD;
                  those resulting in ventricular fibrillation, or causing syncope, or near syncope;&#xD;
&#xD;
               -  Uncontrolled high blood pressure&#xD;
&#xD;
          -  Seizure disorder or any systemic illness affecting brain function during the past 5&#xD;
             years will be exclusionary;&#xD;
&#xD;
          -  Clinical evidence of stroke;&#xD;
&#xD;
          -  Have a history of relevant severe drug allergy or hypersensitivity;&#xD;
&#xD;
          -  Subjects with current clinically significant unstable medical comorbidities, as&#xD;
             indicated by history or physical exam, that pose a potential safety risk to the&#xD;
             subject.&#xD;
&#xD;
        Specific Exclusion Criteria for Controls:&#xD;
&#xD;
        • Exclusionary criteria applied to TBI/PTSD (outlined below) will be applied to controls.&#xD;
&#xD;
        Specific Exclusion Criteria for TBI:&#xD;
&#xD;
        • Presence of PTSD by SCID-I for DSM-IV-TR criteria, or a CAPS score of &gt;30 (Both current&#xD;
        and/or a history of PTSD will be excluded).&#xD;
&#xD;
        Specific Exclusion Criteria for PTSD:&#xD;
&#xD;
          -  Documented or self report history of mild/moderate severe TBI;&#xD;
&#xD;
          -  Any history of head trauma associated with injury onset cognitive complaints; or&#xD;
&#xD;
          -  Loss of consciousness for &gt;5 minutes.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael W. Weiner, MD</last_name>
    <role>Study Director</role>
    <affiliation>University of California, San Francisco</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Paul Aisen, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>USC Alzheimer's Therapeutic Research Institute (ATRI)</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ronald Petersen, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Banner Sun Health Research Institute</name>
      <address>
        <city>Sun City</city>
        <state>Arizona</state>
        <zip>85351</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California, Irvine</name>
      <address>
        <city>Irvine</city>
        <state>California</state>
        <zip>92697</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California, San Diego</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Southern California</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA Palo Alto HSC / Stanford School of Medicine</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California, San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94117</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Georgetown University</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20057</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Howard University</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20060</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wien Center for Clinical Research</name>
      <address>
        <city>Miami Beach</city>
        <state>Florida</state>
        <zip>33140</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Premiere Research Institute</name>
      <address>
        <city>West Palm Beach</city>
        <state>Florida</state>
        <zip>33407</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rush University Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brigham and Women's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cornell Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia University</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Rochester Medical Center</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14620</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Roper St Francis Healthcare</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>U of WA / VA Puget Sound Alzheimer's Disease Research Center</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Wisconsin</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://adni.loni.usc.edu/</url>
    <description>Alzheimer's Disease Neuroimaging Initiative (ADNI)</description>
  </link>
  <link>
    <url>http://www.va.gov</url>
    <description>U.S. Department of Veterans Affairs</description>
  </link>
  <link>
    <url>http://adni.loni.usc.edu/study-design/</url>
    <description>Collaborative Studies: DOD-ADNI</description>
  </link>
  <link>
    <url>https://loni.usc.edu/</url>
    <description>Laboratory of Neuro Imaging (LONI)</description>
  </link>
  <link>
    <url>https://keck.usc.edu/atri/research/studies/</url>
    <description>Alzheimer's Therapeutic Research Institute</description>
  </link>
  <reference>
    <citation>Mueller SG, Weiner MW, Thal LJ, Petersen RC, Jack CR, Jagust W, Trojanowski JQ, Toga AW, Beckett L. Ways toward an early diagnosis in Alzheimer's disease: the Alzheimer's Disease Neuroimaging Initiative (ADNI). Alzheimers Dement. 2005 Jul;1(1):55-66. doi: 10.1016/j.jalz.2005.06.003.</citation>
    <PMID>17476317</PMID>
  </reference>
  <reference>
    <citation>Weiner MW, Aisen PS, Jack CR Jr, Jagust WJ, Trojanowski JQ, Shaw L, Saykin AJ, Morris JC, Cairns N, Beckett LA, Toga A, Green R, Walter S, Soares H, Snyder P, Siemers E, Potter W, Cole PE, Schmidt M; Alzheimer's Disease Neuroimaging Initiative. The Alzheimer's disease neuroimaging initiative: progress report and future plans. Alzheimers Dement. 2010 May;6(3):202-11.e7. doi: 10.1016/j.jalz.2010.03.007.</citation>
    <PMID>20451868</PMID>
  </reference>
  <reference>
    <citation>Jack CR Jr, Knopman DS, Jagust WJ, Shaw LM, Aisen PS, Weiner MW, Petersen RC, Trojanowski JQ. Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. Lancet Neurol. 2010 Jan;9(1):119-28. doi: 10.1016/S1474-4422(09)70299-6.</citation>
    <PMID>20083042</PMID>
  </reference>
  <reference>
    <citation>Vemuri P, Wiste HJ, Weigand SD, Shaw LM, Trojanowski JQ, Weiner MW, Knopman DS, Petersen RC, Jack CR Jr; Alzheimer's Disease Neuroimaging Initiative. MRI and CSF biomarkers in normal, MCI, and AD subjects: predicting future clinical change. Neurology. 2009 Jul 28;73(4):294-301. doi: 10.1212/WNL.0b013e3181af79fb.</citation>
    <PMID>19636049</PMID>
  </reference>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>August 31, 2012</study_first_submitted>
  <study_first_submitted_qc>September 13, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 18, 2012</study_first_posted>
  <last_update_submitted>November 24, 2021</last_update_submitted>
  <last_update_submitted_qc>November 24, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 29, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Southern California</investigator_affiliation>
    <investigator_full_name>Paul Aisen</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>traumatic brain injury (TBI)</keyword>
  <keyword>post traumatic stress disorder (PTSD)</keyword>
  <keyword>Alzheimer's disease (AD)</keyword>
  <keyword>mild cognitive impairment (MCI)</keyword>
  <keyword>dementia</keyword>
  <keyword>biomarkers</keyword>
  <keyword>amyloid</keyword>
  <keyword>neuroimaging</keyword>
  <keyword>cognition disorder</keyword>
  <keyword>tau</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alzheimer Disease</mesh_term>
    <mesh_term>Brain Injuries</mesh_term>
    <mesh_term>Brain Injuries, Traumatic</mesh_term>
    <mesh_term>Cognitive Dysfunction</mesh_term>
    <mesh_term>Stress Disorders, Traumatic</mesh_term>
    <mesh_term>Stress Disorders, Post-Traumatic</mesh_term>
  </condition_browse>
  <!-- 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/NCT01687153
org study id: ADC-044
secondary id: W81XWH-12-2-0012
secondary id: W81XWH-13-1-0259
secondary id: W81XWH-14-1-0462
nct id: NCT01687153
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
Traumatic brain injury (TBI) and post traumatic stress disorder (PTSD) are common combat
      related problems and may be associated with a greater risk of Alzheimer's disease (AD). The
      purpose of this study is to examine the possible connections between TBI and PTSD, and the
      signs and symptoms of AD on Veterans as they age.

      The information collected will help to learn more about how these injuries may affect
      Veterans of the Vietnam War as they grow older, as well as Veterans of the current wars in
      Iraq and Afghanistan, who also have these types of combat related injuries.
The overall long-term goal of this project is to prevent AD, which affects almost 50% of the
      US population over 85 years of age, and is the most common cause of dementia. Clinical signs
      and symptoms of AD include cognitive impairments, especially memory and emotional
      disturbances. In order to accomplish this goal of prevention, a population at risk must be
      identified. Evidence suggests that both TBI and PTSD increase risk for cognitive decline, AD,
      and dementia.

      TBI and PTSD are common problems resulting from military service. Thus far, there have been
      no prospective studies using imaging and biomarkers, which directly measure changes in the
      brain and AD pathology to study the effects of TBI and PTSD. This proposed study will provide
      novel data to test these hypotheses. The results will have major implications for
      identifying, subjects at increased risk for AD, a possible need for early detection of AD in
      military Veterans with histories of TBI and PTSD, and a possible need to employ prevention
      and treatment measures to avoid accelerated development of AD in US military Veterans. This
      study is a first step toward a larger, more comprehensive study of dementia risk factors in
      Veterans. The results will lead to a design and statistical powering of a prevention trial.
      Therefore, this project could be the first step toward the prevention of AD in Veterans, and
      in the general population.
observational model: Cohort
time perspective: Prospective
measure: Rates of change in brain regions based on neuroimaging
time frame: 1 year
description: Rates of change in brain regions based on neuroimaging (magnetic resonance imaging [MRI] and amyloid positron-emission tomography [PET]) to show that those with TBI and/or PTSD have increased evidence for AD compared to Veteran controls
measure: Rates of change in CSF amyloid beta and CSF tau/P tau levels based on biomarkers
time frame: 1 year
description: Rates of change in CSF amyloid beta and CSF tau/P tau levels based on biomarkers such as cerebrospinal fluid (CSF) to show that those with TBI and/or PTSD have increased evidence for AD compared to Veteran controls
measure: Rates of change in neuropsychological measures of memory and general cognitive performance
time frame: 1 Year
description: Rates of change in neuropsychological measures of memory and general cognitive performance based on cognitive measures to show that those with TBI and/or PTSD have increased evidence for AD compared to Veteran controls
measure: Correlations within each group (TBI and PTSD) to assess whether baseline levels or rates of atrophy or cognitive decline are associated with severity of TBI or PTSD
time frame: 1 year
measure: Group differences in the patterns of amyloid deposition (from Florbetapir F 18) and brain atrophy
time frame: 1 year
description: Group differences may give insight into whether TBI or PTSD is associated with reduced brain reserve causing greater cognitive impairments as indicated by neuropsychological test performance.
measure: Group differences in white matter integrity as assessed with Diffusion Tension Imaging (DTI)
time frame: 1 year
description: Group differences in axonal damage as indicated by white matter integrity measured with DTI to determine if axonal injury resulting from TBI is associated with greater amyloid accumulation or whether brain regions with axonal damage have less amyloid accumulation due to disconnection and reduced brain activity.
measure: Rate of change of tau deposition as measured by 18F-AV-1451
time frame: 1 year
description: Rates of change in brain regions based on Tau PET neuroimaging to show that those with TBI and/or PTSD have increased evidence for AD compared to Veteran controls
arm group label: Traumatic Brain Injury (TBI)
description: 65-100 Vietnam Veterans with Traumatic Brain Injury (TBI), but without PTSD, mild cognitive impairment (MCI)/dementia
arm group label: Post Traumatic Stress Disorder (PTSD)
description: 65-100 Vietnam Veterans with PTSD, but without TBI, MCI/dementia
arm group label: Controls
description: 65-100 Vietnam Veteran Controls without TBI or PTSD and comparable in age, gender, and education to the other cohorts
arm group label: TBI w/ MCI
description: 65-100 Vietnam Veterans with TBI but without PTSD who meet the criteria for MCI but not dementia
arm group label: PTSD w/ MCI
description: 65-100 Vietnam Veterans with PTSD but without TBI who meet the criteria for MCI but not dementia
arm group label: Controls w/ MCI
description: 65-100 Vietnam Veteran Controls without TBI or PTSD who meet the criteria for MCI but not dementia, and are comparable in age, gender, and education to the other cohorts
blood, urine, cerobrospinal fluid
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 50 Years
maximum age: 90 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Michael W. Weiner, MD
role: Study Director
affiliation: University of California, San Francisco
last name: Paul Aisen, MD
role: Principal Investigator
affiliation: USC Alzheimer's Therapeutic Research Institute (ATRI)
last name: Ronald Petersen, MD, PhD
role: Principal Investigator
affiliation: Mayo Clinic
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country: United States
url: http://adni.loni.usc.edu/
description: Alzheimer's Disease Neuroimaging Initiative (ADNI)
url: http://www.va.gov
description: U.S. Department of Veterans Affairs
url: http://adni.loni.usc.edu/study-design/
description: Collaborative Studies: DOD-ADNI
url: https://loni.usc.edu/
description: Laboratory of Neuro Imaging (LONI)
url: https://keck.usc.edu/atri/research/studies/
description: Alzheimer's Therapeutic Research Institute
citation: Mueller SG, Weiner MW, Thal LJ, Petersen RC, Jack CR, Jagust W, Trojanowski JQ, Toga AW, Beckett L. Ways toward an early diagnosis in Alzheimer's disease: the Alzheimer's Disease Neuroimaging Initiative (ADNI). Alzheimers Dement. 2005 Jul;1(1):55-66. doi: 10.1016/j.jalz.2005.06.003.
PMID: 17476317
citation: Weiner MW, Aisen PS, Jack CR Jr, Jagust WJ, Trojanowski JQ, Shaw L, Saykin AJ, Morris JC, Cairns N, Beckett LA, Toga A, Green R, Walter S, Soares H, Snyder P, Siemers E, Potter W, Cole PE, Schmidt M; Alzheimer's Disease Neuroimaging Initiative. The Alzheimer's disease neuroimaging initiative: progress report and future plans. Alzheimers Dement. 2010 May;6(3):202-11.e7. doi: 10.1016/j.jalz.2010.03.007.
PMID: 20451868
citation: Jack CR Jr, Knopman DS, Jagust WJ, Shaw LM, Aisen PS, Weiner MW, Petersen RC, Trojanowski JQ. Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. Lancet Neurol. 2010 Jan;9(1):119-28. doi: 10.1016/S1474-4422(09)70299-6.
PMID: 20083042
citation: Vemuri P, Wiste HJ, Weigand SD, Shaw LM, Trojanowski JQ, Weiner MW, Knopman DS, Petersen RC, Jack CR Jr; Alzheimer's Disease Neuroimaging Initiative. MRI and CSF biomarkers in normal, MCI, and AD subjects: predicting future clinical change. Neurology. 2009 Jul 28;73(4):294-301. doi: 10.1212/WNL.0b013e3181af79fb.
PMID: 19636049
responsible party type: Principal Investigator
investigator affiliation: University of Southern California
investigator full name: Paul Aisen
investigator title: Professor
mesh term: Alzheimer Disease
mesh term: Brain Injuries
mesh term: Brain Injuries, Traumatic
mesh term: Cognitive Dysfunction
mesh term: Stress Disorders, Traumatic
mesh term: Stress Disorders, Post-Traumatic