Neural and Behavioral Sequelae of Blast-Related Traumatic Brain Injury

July 8, 2019 updated by: Harvey Levin, Baylor College of Medicine

Hypothesis 1: On fMRI scanning, frontoparietal activation during performance of executive function tasks of working memory, inhibitory control processes, and stimulus-response interference will exhibit greater signal intensity, a wider spatial extent, and more bilateral activation in chronic MTBI than chronic OI participants.

Hypothesis 2: DTI changes, characterized by lower FA and higher MD at the gray-white junction, corpus callosum, central semiovale, and internal capsule, will be seen in MTBI but not in OI subjects.

Hypothesis 3: Increased fMRI activation in chronic MTBI will be correlated with location and severity of disrupted fiber tracks that subserve neural networks associated with each fMRI activation task.

Hypothesis 4: Performance on computerized neuropsychological testing (ANAM) and reaction time measures on fMRI tasks will better discriminate MTBI from OI than standard paper-and pencil tests.

Hypothesis 5: The combination of fMRI, DTI, and ANAM will better discriminate MTBI from OI than each individual method.

Hypothesis 6: More severe brain pathology in MTBI, as measured by neuroimaging (fMRI, DTI) and ANAM test scores, will be associated with less severe PTSD and symptoms.

Study Overview

Status

Completed

Conditions

Detailed Description

Traumatic brain injuries (TBI) are a common occurrence from roadside blasts of improvised explosive devices (IEDs). Like civilian TBI, blast-related TBI can result from mechanical forces in which objects in motion strike the head or the head is forcefully put into motion and strikes an object. TBI from exposure to an explosive blast may also result from a third cause: barotrauma. Blasts produce wave-induced changes in atmospheric pressure, which in turn produce characteristic injuries to vulnerable bodily regions at air-fluid interfaces, such as the middle ear. It is unknown whether the neural and cognitive sequelae of blast-related TBI differ from those resulting from mechanically-induced TBI commonly observed in civilian accidents. Understanding the potentially unique sequelae of blast-related TBI is critical for accurate diagnosis and designing effective pharamacological and neurorehabilitation interventions.

In the proposed cross-sectional study, we aim to apply neurobehavioral testing and advanced MRI techniques [task-activated functional MRI (fMRI) and diffusion tensor imaging (DTI)] to gain a comprehensive understanding of the neural changes underlying blast-related MTBI. This will be accomplished by comparing neurobehavioral and neuroimaging findings obtained from military personnel who have experienced a blast injury with those obtained from civilians who have experienced TBI from motor vehicle accidents and from military and civilian control participants with orthopedic injuries. We will accomplish this goal by conducting advanced neuroimaging (task-activated fMRI and DTI fiber tracking) and neurobehavioral testing (computerized assessment and standard neuropsychological testing) on 120 chronic trauma patients: 30 military MTBI patients who have experienced blast injuries, 30 civilian MTBI patients with mechanical closed head injuries, and 30 military and 30 civilian patients with orthopedic injuries.

Study Type

Observational

Enrollment (Actual)

60

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

This is a prospective, observational study using a cross-sectional design to compare brain imaging and neuropsychological findings at 12 to 72 months post-injury in four groups of at least 30 patients each: two groups of military patients who have sustained mild to moderate TBI (milMTBI) or orthopedic injury or uninjured veterans, reservists, or service members (milControl) and two groups of civilian patients who had MTBI (civMTBI) or OI (civOI).

Description

Inclusion Criteria:

Inclusion Criteria for milMTBI

1. GCS score 9-15 (if available) 2. Brain injury due to blast 3. Current age 18-45 4. Right-handed 5. Post-injury interval 12-72 months 6. Duration of Loss of Consciousness (LOC) < 24 hours 7. Duration of Posttraumatic Amnesia (PTA)< 7 days 8. No intracranial surgery 9. No brain lesions on computer tomography (CT) scan (if available) 10. Extracranial Injuries by Abbreviated Injury Scale (AIS) <3 (non-head)

Inclusion Criteria for civlMTBI

1. GCS score 9-15 (if available) 2. Non-blast brain injury 3. Current age 18-45 4. Right-handed 5. Post-injury interval 12-72 months 6. LOC < 24 hours 7. PTA< 7 days 8. No intracranial surgery 9. No brain lesions on CT scan (if available) 10. Extracranial Injuries by AIS <3 (non-head)

Inclusion Criteria for milControl and civOI

1. No history of brain injury 2. Non-blast extracranial injury or no injury 3. Current age 18-45 4. Right-handed 5. Post-injury interval 12-72 months 6. LOC -none 7. PTA- none 8. No intracranial surgery 9. CT scan normal (if done) 10. Extracranial Injuries by AIS <3 (non-head)

Exclusion Criteria:

1) Not fluent in English 2) Non-right hande 3) AIS score equal or higher 4 for body parts other than head 4) Neurologic deficit other than TBI (MTBI, OI groups); no LOC or PTA (MTBI groups) 5) Blood alcohol level > 200 mg/dL 6) Previous hospitalization for head injury 7) Pregnancy when screened prior to brain imaging 8) Pre-existing neurologic disorder associated with cerebral dysfunction and/or cognitive deficit (e.g., cerebral palsy, mental retardation, epilepsy) or diagnosed dyslexia 9) Pre-existing severe psychiatric disorder (bipolar disorder, schizophrenia) as determined by the Structured Clinical Interview for Depression 10) Penetrating gunshot wound to the brain 11) Contraindications to undergoing MRI, including implant of metal or marked agitation observed by research assistant. 12) Illegal alien 13) Hypoxia for 30 minutes or longer after resuscitation PO2 < 96 mmHg 14) Hypotension for 30 minutes or longer after resuscitation (systolic blood pressure more than 2SDs below mean for age)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Other

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Brain activation on Stop Signal Reaction Time Task (SSRT)
Time Frame: 12-24 months post-injury
fMRI measuring brain activation associated with performance of SSRT
12-24 months post-injury
Brain activation on Sternberg Item Recognition Task (SIRT)
Time Frame: 12-24 months post-injury
fMRI measuring brain activation associated with performance of SIRT
12-24 months post-injury

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Neurobehavioral Symptom Inventory
Time Frame: 12-24 months post-injury
self-report of various domains of emotional status
12-24 months post-injury
Post-traumatic Symptom Checklist-Civilian (PCL-C)
Time Frame: 12-24 months post-injury
Checklist of posttraumatic stress symptoms
12-24 months post-injury
Center for the Epidemiological Center for Study of Depression (CES-D)
Time Frame: 12-24 months post-injury
Self-report measure of depression
12-24 months post-injury
Symbol Digit Modalities Test (SDMT)
Time Frame: 12-24 months post-injury
Measure of processing speed
12-24 months post-injury
Trail Making Test A and B
Time Frame: 12-24 months post-injury
Measure of visuoperceptive performance and speed
12-24 months post-injury
Controlled Oral Word Association
Time Frame: 12-24 months post-injury
Measure of verbal fluency
12-24 months post-injury
California Verbal Learning Test 2
Time Frame: 12-24 months post-injury
Verbal learning test
12-24 months post-injury

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

Investigators

  • Principal Investigator: Harvey Levin, PhD, Baylor College of Medicine
  • Principal Investigator: Steven Rao, PhD, The Cleveland Clinic

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2012

Primary Completion (Actual)

May 1, 2014

Study Completion (Actual)

May 1, 2014

Study Registration Dates

First Submitted

March 19, 2015

First Submitted That Met QC Criteria

July 8, 2019

First Posted (Actual)

July 9, 2019

Study Record Updates

Last Update Posted (Actual)

July 9, 2019

Last Update Submitted That Met QC Criteria

July 8, 2019

Last Verified

March 1, 2015

More Information

Terms related to this study

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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