A Study of Brain Aging in Vietnam War Veterans

NCT ID: NCT01687153

Last Updated: 2021-11-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

289 participants

Study Classification

OBSERVATIONAL

Study Start Date

2012-10-31

Study Completion Date

2021-09-21

Brief Summary

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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.

Detailed Description

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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.

Conditions

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

Keywords

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traumatic brain injury (TBI) post traumatic stress disorder (PTSD) Alzheimer's disease (AD) mild cognitive impairment (MCI) dementia biomarkers amyloid neuroimaging cognition disorder tau

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Traumatic Brain Injury (TBI)

65-100 Vietnam Veterans with Traumatic Brain Injury (TBI), but without PTSD, mild cognitive impairment (MCI)/dementia

No interventions assigned to this group

Post Traumatic Stress Disorder (PTSD)

65-100 Vietnam Veterans with PTSD, but without TBI, MCI/dementia

No interventions assigned to this group

Controls

65-100 Vietnam Veteran Controls without TBI or PTSD and comparable in age, gender, and education to the other cohorts

No interventions assigned to this group

TBI w/ MCI

65-100 Vietnam Veterans with TBI but without PTSD who meet the criteria for MCI but not dementia

No interventions assigned to this group

PTSD w/ MCI

65-100 Vietnam Veterans with PTSD but without TBI who meet the criteria for MCI but not dementia

No interventions assigned to this group

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

No interventions assigned to this group

Eligibility Criteria

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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.


* 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.


* 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


* 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.


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


• 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).


* 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.
Minimum Eligible Age

50 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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United States Department of Defense

FED

Sponsor Role collaborator

Telemedicine & Advanced Technology Research Center

OTHER

Sponsor Role collaborator

Northern California Institute of Research and Education

OTHER

Sponsor Role collaborator

San Francisco Veterans Affairs Medical Center

FED

Sponsor Role collaborator

Alzheimer's Therapeutic Research Institute

OTHER

Sponsor Role collaborator

University of Southern California

OTHER

Sponsor Role lead

Responsible Party

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Paul Aisen

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Michael W. Weiner, MD

Role: STUDY_DIRECTOR

University of California, San Francisco

Paul Aisen, MD

Role: PRINCIPAL_INVESTIGATOR

USC Alzheimer's Therapeutic Research Institute (ATRI)

Ronald Petersen, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

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Banner Sun Health Research Institute

Sun City, Arizona, United States

Site Status

University of California, Irvine

Irvine, California, United States

Site Status

University of California, San Diego

La Jolla, California, United States

Site Status

University of Southern California

Los Angeles, California, United States

Site Status

VA Palo Alto HSC / Stanford School of Medicine

Palo Alto, California, United States

Site Status

University of California, San Francisco

San Francisco, California, United States

Site Status

Georgetown University

Washington D.C., District of Columbia, United States

Site Status

Howard University

Washington D.C., District of Columbia, United States

Site Status

Wien Center for Clinical Research

Miami Beach, Florida, United States

Site Status

Premiere Research Institute

West Palm Beach, Florida, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

Cornell Medical Center

New York, New York, United States

Site Status

Columbia University

New York, New York, United States

Site Status

University of Rochester Medical Center

Rochester, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Roper St Francis Healthcare

Charleston, South Carolina, United States

Site Status

U of WA / VA Puget Sound Alzheimer's Disease Research Center

Seattle, Washington, United States

Site Status

University of Wisconsin

Madison, Wisconsin, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 17476317 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20451868 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20083042 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19636049 (View on PubMed)

Related Links

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http://adni.loni.usc.edu/

Alzheimer's Disease Neuroimaging Initiative (ADNI)

http://www.va.gov

U.S. Department of Veterans Affairs

https://loni.usc.edu/

Laboratory of Neuro Imaging (LONI)

https://keck.usc.edu/atri/research/studies/

Alzheimer's Therapeutic Research Institute

Other Identifiers

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W81XWH-12-2-0012

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

W81XWH-13-1-0259

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

W81XWH-14-1-0462

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

ADC-044

Identifier Type: -

Identifier Source: org_study_id