Mild Traumatic Brain Injury and Post-Traumatic Stress Disorder

Status:	Recruiting
Conditions:	Neurology, Psychiatric
Therapuetic Areas:	Neurology, Psychiatry / Psychology
Healthy:	No
Age Range:	18 - 50
Updated:	11/30/2013
Start Date:	February 2012
Contact:	Jacquin Jones, R.N.
Email:	jjonesl@cc.nih.gov
Phone:	(301) 496-9491

Imaging the GABAergic System Using 11C-flumazenil PET to Assess the Role of Mild Traumatic Brain Injury in the Development of Post Traumatic Stress Disorder

Background:

- Some people who have a traumatic brain injury (TBI) recover completely. Others, however,
develop post-traumatic stress disorder (PTSD), with anxiety and depression. Research
suggests that levels of a brain chemical called GABA may differ in people with PTSD compared
to those without PTSD. Researchers want to see if TBI can affect GABA in the brain and help
develop PTSD. To look at the brain, researchers will use imaging studies with the chemical
11C-Flumazenil, which will help the scan show GABA levels in the brain.

Objectives:

- To study the relationship between PTSD and TBI.

Eligibility:

The subjects will be recruited from the Walter Reed National Military Medical Center
(WRNMMC).

- Individuals between 18 and 50 years of age who have PTSD and/or had a mild TBI.

- Healthy individuals between 18 and 50 years of age who have no history TBI and no
history of PTSD.

Design:

- Participants will be screened with a physical exam and medical history. Urine and
breath samples will also be collected.

- Participants will have two imaging studies, on the same day if possible. The first will
be a magnetic resonance imaging scan to look at the brain. The second will be a
positron emission tomography scan with the study chemical to look at GABA pathways in
the brain.

Objective

The primary objective of this study is to investigate the potential role of mild traumatic
brain injury (mTBI) in the development of post-traumatic stress disorder (PTSD). We will
characterize the central GABAergic system function in patients with PTSD after TBI
(TBI-PTSD), subjects with TBI only (TBI-no PTSD), subjects with PTSD only (PTSD-no TBI ),
and healthy non-TBI non-PTSD subjects (HC), using PET imaging with (11)C-Flumazenil (FMZ).
Our hypothesis is that neuronal and axonal damage due to TBI results in GABAergic system
dysfunction which could potentially lead to or contribute to the development of PTSD. We
will also correlate the degree of (11)C-FMZ binding abnormalities with time elapsed since
the original physical or psychological trauma in TBI-PTSD and PTSD-no TBI patients.

Study Population

Fifty-six male and female adult subjects will be recruited: 14 subjects with PTSD following
an episode of non-penetrating mTBI (TBI-PTSD), 14 subjects with mTBI but no history of PTSD
(TBI-no PTSD), 14 subjects with PTSD but no history of TBI (PTSD-no TBI), and 14 healthy
volunteers (HC) with no PTSD and no history of TBI. The subjects will be recruited from the
Walter Reed National Military Medical Center (WRNMMC).

Design

This is a prospective case-control study of the four subject groups mentioned above.
Subjects will be stratified according to detailed psychiatric evaluation performed at
WRNMMC. Subjects will not be treated with experimental therapies as part of the research
study. This study will provide no direct benefit to subjects.

Outcome Measures

The main outcome measure will be (11)C-FMZ binding potential (BP) differences among these
four subject groups. Other outcome measures will include Magnetic Resonance Imaging (MRI)
anatomical findings and the correlation of (11)C-FMZ binding abnormalities with time elapsed
since the original physical trauma in TBI-PTSD group or original psychological trauma in
PTSD only group.

- All participants must be enrolled in the protocol at Walter Reed National Military
Medical Center.

INCLUSION CRITERIA:

TBI-PTSD SUBJECTS:

Subjects in this group must meet the following inclusion criteria:

- Documented diagnosis of non-penetrating mTBI within the last two years.

- Diagnosis of PTSD (which is known to have occurred following the mTBI event) as per
the diagnostic criteria followed by protocol number NNMC.2011.0035 at WRNMMC

- Age 18-50 years of age

TBI-no PTSD SUBJECTS:

Subjects in this group must meet the following inclusion criteria:

- No history of PTSD or other major psychiatric disorders

- Mild TBI diagnosis.

- Age 18-50 years of age

PTSD-no TBI subjects:

Subjects in this group must meet the following inclusion criteria:

- No history of TBI

- PTSD diagnosis as per the diagnostic criteria followed by protocol number
NNMC.2011.0035 at WRNMMC.

- Age 18-50 years of age

Healthy Control subjects:

Subjects in this group must meet the following inclusion criteria:

- No history of penetrating or non-penetrating head trauma.

- Exclusion of PTSD or other serious psychiatric disorders by psychiatric evaluation as
per the diagnostic criteria followed by protocol number NNMC.2011.0035 at WRNMMC

- Age 18-50 years of age

EXCLUSION CRITERIA:

All Subjects:

Subjects are not eligible for participation in this research study if any of the following
conditions exist:

- Subjects with history of strokes, brain tumors, seizure and other neurologic problems

- Subjects with serious medical illness such as heart disease, lung disease, kidney
disease, a blood disorder like multiple myeloma, diabetes or blood vessel disease.

- Contraindication(s) to MRI scanning, including pacemakers or other implanted
electrical devices, brain stimulators, some types of dental implants, aneurysm clips
(metal clips on the wall of a large artery), metallic prostheses (including metal
pins and rods, heart valves, and cochlear implants), permanent eyeliner, implanted
delivery pump, or shrapnel fragments, morbid obesity and severe claustrophobia).

- Pregnant women or women who are breast-feeding.

- History of taking anxiolytics (namely benzodiazepines and barbiturates),
anti-depressants or anti-psychotic drugs, unless abstinence for at least 4 weeks
prior to the scan.

- History of taking GABAergic drugs such as gabapentin, vigabatrin, tiagabine,
lamotrigine, pregabalin and others unless abstinence for at least 4 weeks prior to
the scan.

- Blood alcohol concentration > 0.0 using a breathalyzer on the day of the scan.

- Evidence of heavy alcohol use based on AUDIT questionnaire (score > 8)

- Evidence of drug dependence based on the urine toxicology screen.

- History of previous radiation exposure from any source that, when combined with
PET/CT scan, would exceed NIH RSC limits.

- Lifetime or current diagnosis of schizophrenia or other psychotic disorder, or
bipolar disorder

- Subjects who cannot give their own consent.

We found this trial at

sites

Walter Reed National Medical Center

Bethesda, Maryland 20301

from

Bethesda, MD