Traumatic Brain Injury Clinical Trial
Official title:
ADVANCED MRI IN BLAST-RELATED TBI
Thousands of soldiers, marines, and other military personnel have had injuries to the brain
due the wars in Iraq and Afghanistan. In addition, 1.5 million civilians per year in the
United States have traumatic brain injuries caused by car accidents, falls, sports-related
injuries or assaults. There are important advances in technology that we think will help us
learn a lot more about these injuries. One such advance involves new types of MRI scans that
we think will be able to show what has happened to the brain after trauma more clearly that
regular scans can. These first new scan is called diffusion tensor imaging, which shows
injury to the axons (the wiring of the brain). The second new scan is called resting-state
functional MRI correlation analysis, which shows how well various parts of the brain are
connected to each other. Importantly, the new types of scans can be done using regular
scanners that we already have in every major hospital. The innovation is entirely in how the
scanners are used and how the resulting pictures are analyzed on a computer after they have
been taken.
Our overall goal is to see whether these new MRI scans will be useful for people who have had
traumatic brain injuries. We have already tested them on some civilian brain injury patients
and found them to be very helpful. For this study, we will test them on military personnel
who have had traumatic brain injuries caused by explosions. The specific goal will be to see
if the amount of injury we see can be used to predict how well the patients will do overall
over the next 6-12 months. We think with the new scans we will be able to predict overall
outcomes better than with regular scans and other information. A related goal will be to see
whether injuries to specific parts of the brain seen by these new scans can be used to
predict whether patients will be likely to have specific problems like memory loss, attention
deficit, depression, or post-traumatic stress disorder. A final goal will be to repeat the
scans 6-12 months later to see whether the new MRI scans can show whether the injuries to the
brain have healed, gotten worse, or stayed the same.
If the study is successful, it will show that these new MRI techniques can to be used to make
earlier and more accurate diagnoses of traumatic brain injury, predictions of the sorts of
problems that are likely to occur after brain injury, and assessments of how severe the
injuries are.
This study will help traumatic brain injury patients. It will be most useful for military
personnel who have had brain injuries due to explosions. It is highly likely that it will
also be useful for younger adults who have had brain injuries due to other causes like car
accidents, sports-related concussions, falls, or assaults. It is possible that but not known
for sure whether it will help young children or older adults with traumatic brain injuries.
These new scans could help with decisions about whether military personnel can return to
duty, what sort of rehabilitation would benefit them most, and what family members should
watch for and expect. This could become used in some hospitals within 2 years, and could
become standard in every major hospital within 5 years.
The new scans could also be helpful in developing new treatments. For example, if a new drug
works by blocking injury to the axons, it would be a good idea to test on people who have
injury to their axons. Right now we have no good way to tell who these people are, and so a
new drug like this would get tested on lots of people who don't have injured axons, along
with those who do. This would make it harder to tell if the new drug is working. With the new
scans we should be able to tell who has injured axons, tell how severe the injury is, and
figure out whom to test the drugs on. It will likely take 10 years or more to develop new
drugs like this.
Further in the future, the new scans could be used to help guide surgery to implant computer
chips to help rewire the brain. We don't know how long this will take, but estimate 15-20
years or more.
Overall MRI scanning is very safe and has no known major risks. Because the scanner uses
strong magnets, anyone with metal objects in their bodies can't be scanned, as this could be
dangerous. We will make sure that no one with metal objects in their bodies is included in
the study. There can be some psychological risks involved in taking tests and answering
questions, but these are usually mild and can be managed. There is always a risk that
important confidential information will be made public and that this could have consequences.
We will do everything possible to maintain confidentiality. Nearly all of the information
will only be identified using a code number and not by the name of the person, and all of it
will be kept securely.
Background: In traumatic brain injury, axonal damage is a major pathophysiological process
and may be a primary cause of adverse neurological outcomes. However, traumatic axonal injury
and its effects on brain functional connectivity are very difficult to directly detect and
quantify in living patients. Diffusion tensor imaging (DTI) appears to have great promise
with regard to detecting axonal injury. Resting-state fMRI correlation analysis likewise may
be a powerful and broadly applicable method for investigating brain functional connectivity.
In our preliminary studies, these two techniques have been successfully used together in
several civilian TBI patients. They appear to synergistically cross validate each other;
disrupted functional connectivity underlying focal neurological deficits were revealed using
resting-state fMRI correlation analysis while DTI demonstrated the axonal injury responsible
for the disruptions. Conventional MRI and CT entirely failed to explain many of these
deficits. This cross validation is important as it adds confidence to the interpretation of
the results. Without resting-state fMRI correlation analysis, the consequences of apparent
axonal injury on DTI for the functional connectivity of the brain may not be clear; the
axonal injury could be in white matter tracts that are redundant, or not severe enough to be
functionally important. Without DTI, the cause of a disruption in connectivity seen using
resting-state fMRI correlation analysis will likewise not always be known; processes other
than traumatic axonal injury could be responsible. Both of these advanced techniques along
with a full conventional MRI can be performed on standard clinical MRI scanners in
approximately 45 minutes per patient. Apart from in our preliminary studies, resting-state
fMRI and DTI have not been used together to investigate traumatic brain injury.
Objective/Hypothesis: The objective of this proposal is to test these two advanced MRI
methods, DTI and resting-state fMRI, in active-duty military blast-related TBI patients
acutely after injury and correlate findings with TBI-related clinical outcomes 6-12 months
later. These methods may add clinically useful predictive information following traumatic
brain injury that could be of assistance in standardizing diagnostic criteria for TBI, making
return-to-duty triage decisions, guiding post-injury rehabilitation, and developing novel
therapeutics. The overarching hypothesis guiding this project is that traumatic axonal injury
is a principal cause of impaired brain function following blast-related TBI. Specific
hypotheses to be tested are:
1. DTI and resting-state fMRI correlation analysis will noninvasively reveal abnormalities
that are not present on CT or conventional MRI acutely following blast-related TBI.
2. Specific patterns of acute axonal injury (on DTI) causing disruption of brain functional
connectivity (on resting-state fMRI correlation analysis) will predict specific
neurological, neuropsychological, and psychiatric deficits and disorders.
3. The overall burden of acute axonal injury and disrupted brain functional connectivity
will strongly predict overall 6-12 month clinical outcome.
Specific Aims: 1) to obtain DTI, resting-state fMRI and conventional MRI scans acutely after
blast-related TBI in active-duty military personnel presenting to Landstuhl Regional Medical
Center (LRMC).
2) to collect detailed clinical information on TBI-related outcomes 6-12 months after
injuries.
3) to extensively analyze the acute imaging predictors and correlates of 6-12 month clinical
outcomes.
Study Design: We propose a prospective, observational study of 80 active duty military
personnel who have sustained blast-related TBI. Initial scans will be performed within 4 days
of injury at LRMC. Follow-up will occur monthly by telephone and in person at Washington
University 6-12 months after injury. Clinical information on TBI outcomes collected will
include global outcome assessments, neuropsychological testing for memory, attention and
executive function deficits, motor performance measures, and clinician administered rating
scales for depression and post-traumatic stress disorder. Controls will include 1) an
additional group of 20 active duty military personnel with other injuries, but who have not
had TBI, and 2) age, gender and education-based norms for standardized test and assessment
results. Repeat DTI, resting-state fMRI, and conventional MRI will be performed to track the
evolution of the injuries. Analysis approaches will include prespecified hypotheses based on
known brain anatomical-clinical correlations and several exploratory approaches, as the
structural bases for many post-traumatic neurological and neuropsychological deficits are not
well understood. Non-parametric correlational statistical methods and rigorous correction for
multiple comparisons will be employed. Expert collaborators and logistics coordinators will
be or have already been recruited. Confidentiality and privacy will be tightly controlled.
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Terminated |
NCT03052712 -
Validation and Standardization of a Battery Evaluation of the Socio-emotional Functions in Various Neurological Pathologies
|
N/A | |
Recruiting |
NCT05503316 -
The Roll of Balance Confidence in Gait Rehabilitation in Persons With a Lesion of the Central Nervous System
|
N/A | |
Completed |
NCT04356963 -
Adjunct VR Pain Management in Acute Brain Injury
|
N/A | |
Completed |
NCT03418129 -
Neuromodulatory Treatments for Pain Management in TBI
|
N/A | |
Terminated |
NCT03698747 -
Myelin Imaging in Concussed High School Football Players
|
||
Recruiting |
NCT05130658 -
Study to Improve Ambulation in Individuals With TBI Using Virtual Reality -Based Treadmill Training
|
N/A | |
Recruiting |
NCT04560946 -
Personalized, Augmented Cognitive Training (PACT) for Service Members and Veterans With a History of TBI
|
N/A | |
Completed |
NCT05160194 -
Gaining Real-Life Skills Over the Web
|
N/A | |
Recruiting |
NCT02059941 -
Managing Severe Traumatic Brain Injury (TBI) Without Intracranial Pressure Monitoring (ICP) Monitoring Guidelines
|
N/A | |
Recruiting |
NCT03940443 -
Differences in Mortality and Morbidity in Patients Suffering a Time-critical Condition Between GEMS and HEMS
|
||
Recruiting |
NCT03937947 -
Traumatic Brain Injury Associated Radiological DVT Incidence and Significance Study
|
||
Completed |
NCT04465019 -
Exoskeleton Rehabilitation on TBI
|
||
Recruiting |
NCT04530955 -
Transitioning to a Valve-Gated Intrathecal Drug Delivery System (IDDS)
|
N/A | |
Recruiting |
NCT03899532 -
Remote Ischemic Conditioning in Traumatic Brain Injury
|
N/A | |
Suspended |
NCT04244058 -
Changes in Glutamatergic Neurotransmission of Severe TBI Patients
|
Early Phase 1 | |
Completed |
NCT03307070 -
Adapted Cognitive Behavioral Treatment for Depression in Patients With Moderate to Severe Traumatic Brain Injury
|
N/A | |
Recruiting |
NCT04274777 -
The Relationship Between Lipid Peroxidation Products From Traumatic Brain Injury and Secondary Coagulation Disorders
|
||
Withdrawn |
NCT05062148 -
Fundamental and Applied Concussion Recovery Modality Research and Development: Applications for the Enhanced Recovery
|
N/A | |
Withdrawn |
NCT04199130 -
Cognitive Rehabilitation and Brain Activity of Attention-Control Impairment in TBI
|
N/A | |
Withdrawn |
NCT03626727 -
Evaluation of the Efficacy of Sodium Oxybate (Xyrem®) in Treatment of Post-traumatic Narcolepsy and Post-traumatic Hypersomnia
|
Early Phase 1 |