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A Study of Brain Aging in Vietnam War Veterans (DOD-ADNI)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2016 by University of Southern California
Sponsor:
Collaborators:
United States Department of Defense
Telemedicine & Advanced Technology Research Center
Northern California Institute of Research and Education
San Francisco Veterans Affairs Medical Center
Alzheimer's Therapeutic Research Institute
Information provided by (Responsible Party):
Paul Aisen, University of Southern California
ClinicalTrials.gov Identifier:
NCT01687153
First received: August 31, 2012
Last updated: November 7, 2016
Last verified: November 2016
  Purpose

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.


Condition
Traumatic Brain Injury
Post Traumatic Stress Disorder
Alzheimer's Disease
Mild Cognitive Impairment

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
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)

Resource links provided by NLM:


Further study details as provided by University of Southern California:

Primary Outcome Measures:
  • Rates of change in brain regions based on neuroimaging [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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

  • Rates of change in CSF amyloid beta and CSF tau/P tau levels based on biomarkers [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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

  • Rates of change in neuropsychological measures of memory and general cognitive performance [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Group differences in the patterns of amyloid deposition (from Florbetapir F 18) and brain atrophy [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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.

  • Group differences in white matter integrity as assessed with Diffusion Tension Imaging (DTI) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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.

  • Rate of change of tau deposition as measured by 18F-AV-1451 [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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


Biospecimen Retention:   Samples With DNA
blood, urine, cerobrospinal fluid

Estimated Enrollment: 420
Study Start Date: October 2012
Estimated Study Completion Date: September 2017
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Groups/Cohorts
Traumatic Brain Injury (TBI)
65-100 Vietnam Veterans with Traumatic Brain Injury (TBI), but without PTSD, mild cognitive impairment (MCI)/dementia
Post Traumatic Stress Disorder (PTSD)
65-100 Vietnam Veterans with PTSD, but without TBI, MCI/dementia
Controls
65-100 Vietnam Veteran Controls without TBI or PTSD and comparable in age, gender, and education to the other cohorts
TBI w/ MCI
65-100 Vietnam Veterans with TBI but without PTSD who meet the criteria for MCI but not dementia
PTSD w/ MCI
65-100 Vietnam Veterans with PTSD but without TBI who meet the criteria for MCI but not dementia
Controls w/ MCI
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   50 Years to 90 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Vietnam Veterans
Criteria

Participants will be classified as either controls, TBI, or PTSD. General Inclusion/Exclusion Criteria will apply to all groups, with specific criteria for each group as described below.

Inclusion Criteria:

General (applies to each cohort):

  • Subjects must be Veterans of the Vietnam War, 50-90 years of age. (Subjects 60-80 years of age will be selected first, while subjects <60 or >80 years of age will be added if recruitment numbers are too low in the 60-80 age range);
  • Must live within 150 miles of the closest ADNI clinic in subject's area.

Specific Inclusion Criteria for Controls:

  • Comparable in age, gender, and education with TBI and PTSD groups;
  • May be receiving Veterans Affairs (VA) disability payments for something other than TBI or PTSD - or no disability at all.

Specific Inclusion Criteria for TBI:

  • Subjects must have a documented history of moderate-severe non-penetrating TBI, which occurred during military service in Vietnam (identified from the Department of Defense or VA records);
  • TBI will be defined as:

    • Loss of consciousness,
    • Post-traumatic amnesia >24 hours, OR
    • Alteration of consciousness or mental state >24 hours

Specific Inclusion Criteria for PTSD:

  • Subjects who meet the Structured Clinical Interview 1 of the Diagnositic and Statistical Manual of Mental Disorders, Version IV, (Axis 1) - Text Revision [SCID-I of the DSM-IV-TR] criteria for current/chronic PTSD (identified by records, and verified by our telephone assessments);
  • In addition to meeting DSM-IV-TR criteria for current/chronic PTSD, subjects must have a minimum current Clinician Administered PTSD Scale (CAPS) score of 50 as determined by telephone assessment;
  • The PTSD symptoms contributing to the PTSD Diagnosis and Current CAPS score must be related to a Vietnam War related trauma.

Exclusion Criteria:

General (applies to each cohort):

  • MCI/dementia;
  • History of psychosis or bipolar affective disorder;
  • History of alcohol or substance abuse/dependence within the past 5 years (by DSM-IV-TR criteria) or a prior prolonged history of abuse;
  • MRI-related exclusions: aneurysm clips, metal implants that are determined to be unsafe for MRI; and/or claustrophobia;
  • Contraindications for lumbar puncture, PET scan, or other procedures in this study;
  • Any major medical condition must be stable for at least 4 months prior to enrollment. These include but are not limited to clinically significant hepatic, renal, pulmonary, metabolic or endocrine disease, cancer, HIV infection and AIDS, as well as cardiovascular disease, including:

    • cardiac surgery or myocardial infarction within the last 4 weeks;
    • unstable angina;
    • acute decompensated congestive heart failure or class IV heart failures;
    • current significant cardiac arrhythmia or conduction disturbance particularly those resulting in ventricular fibrillation, or causing syncope, or near syncope;
    • Uncontrolled high blood pressure
  • Seizure disorder or any systemic illness affecting brain function during the past 5 years will be exclusionary;
  • Clinical evidence of stroke;
  • Have a history of relevant severe drug allergy or hypersensitivity;
  • Subjects with current clinically significant unstable medical comorbidities, as indicated by history or physical exam, that pose a potential safety risk to the subject.

Specific Exclusion Criteria for Controls:

• Exclusionary criteria applied to TBI/PTSD (outlined below) will be applied to controls.

Specific Exclusion Criteria for TBI:

• Presence of PTSD by SCID-I for DSM-IV-TR criteria, or a CAPS score of >30 (Both current and/or a history of PTSD will be excluded).

Specific Exclusion Criteria for PTSD:

  • Documented or self report history of mild/moderate severe TBI;
  • Any history of head trauma associated with injury onset cognitive complaints; or
  • Loss of consciousness for >5 minutes.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01687153

Contacts
Contact: Jacqueline Hayes 415-221-4810 ext 4593 Jacqueline.Hayes@va.gov

Locations
United States, Arizona
Banner Sun Health Research Institute Enrolling by invitation
Sun City, Arizona, United States, 85351
United States, California
University of California, Irvine Enrolling by invitation
Irvine, California, United States, 92697
University of California, San Diego Enrolling by invitation
La Jolla, California, United States, 92093
University of Southern California Enrolling by invitation
Los Angeles, California, United States, 90033
Stanford University Enrolling by invitation
Palo Alto, California, United States, 94304
University of California, San Francisco Recruiting
San Francisco, California, United States, 94117
Contact: Samuel Stark    415-502-7149    Samuel.Stark@ucsf.edu   
Contact: Jonathan Elofson       jelofson@memory.ucsf.edu   
Principal Investigator: Howard Rosen, MD         
United States, District of Columbia
Georgetown University Enrolling by invitation
Washington, District of Columbia, United States, 20057
Howard University Enrolling by invitation
Washington, District of Columbia, United States, 20060
United States, Florida
Wien Center for Clinical Research Enrolling by invitation
Miami Beach, Florida, United States, 33140
Premiere Research Institute Enrolling by invitation
West Palm Beach, Florida, United States, 33407
United States, Illinois
Rush University Medical Center Enrolling by invitation
Chicago, Illinois, United States, 60612
United States, Massachusetts
Brigham and Women's Hospital Enrolling by invitation
Boston, Massachusetts, United States, 02115
United States, New York
Cornell Medical Center Enrolling by invitation
New York, New York, United States, 10021
Columbia University Enrolling by invitation
New York, New York, United States, 10032
University of Rochester Medical Center Enrolling by invitation
Rochester, New York, United States, 14620
United States, North Carolina
Duke University Medical Center Enrolling by invitation
Durham, North Carolina, United States, 27710
United States, South Carolina
Ralph H. Johnson Veterans Affairs Medical Center (VAMC Charleston) Enrolling by invitation
North Charleston, South Carolina, United States, 29401
United States, Washington
U of WA / VA Puget Sound Alzheimer's Disease Research Center Enrolling by invitation
Seattle, Washington, United States, 98108
United States, Wisconsin
University of Wisconsin Enrolling by invitation
Madison, Wisconsin, United States, 53705
Sponsors and Collaborators
University of Southern California
United States Department of Defense
Telemedicine & Advanced Technology Research Center
Northern California Institute of Research and Education
San Francisco Veterans Affairs Medical Center
Alzheimer's Therapeutic Research Institute
Investigators
Study Director: Michael W. Weiner, MD University of California, San Francisco
Principal Investigator: Paul Aisen, MD USC Alzheimer's Therapeutic Research Institute (ATRI)
Principal Investigator: Ronald Petersen, MD, PhD Mayo Clinic
  More Information

Additional Information:
Publications:
Responsible Party: Paul Aisen, Professor, University of Southern California
ClinicalTrials.gov Identifier: NCT01687153     History of Changes
Other Study ID Numbers: ADC-044  W81XWH-12-2-0012  W81XWH-13-1-0259  W81XWH-14-1-0462 
Study First Received: August 31, 2012
Last Updated: November 7, 2016
Health Authority: United States: Data and Safety Monitoring Board
United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of Southern California:
traumatic brain injury (TBI)
post traumatic stress disorder (PTSD)
Alzheimer's disease (AD)
mild cognitive impairment (MCI)
dementia
biomarkers
amyloid
neuroimaging
cognition disorder
tau

Additional relevant MeSH terms:
Wounds and Injuries
Alzheimer Disease
Brain Injuries
Stress Disorders, Traumatic
Cognition Disorders
Mild Cognitive Impairment
Stress Disorders, Post-Traumatic
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Craniocerebral Trauma
Trauma, Nervous System
Trauma and Stressor Related Disorders

ClinicalTrials.gov processed this record on December 06, 2016