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出境医 / 临床实验 / Neural and Behavioral Sequelae of Blast-Related Traumatic Brain Injury

Neural and Behavioral Sequelae of Blast-Related Traumatic Brain Injury

Study Description
Brief Summary:

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.


Condition or disease
TBI

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 Design
Layout table for study information
Study Type : Observational
Actual Enrollment : 60 participants
Observational Model: Case-Control
Time Perspective: Other
Official Title: Neural and Behavioral Sequelae of Blast-Related Traumatic Brain Injury
Study Start Date : June 2012
Actual Primary Completion Date : May 2014
Actual Study Completion Date : May 2014
Arms and Interventions
Outcome Measures
Primary Outcome Measures :
  1. 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

  2. Brain activation on Sternberg Item Recognition Task (SIRT) [ Time Frame: 12-24 months post-injury ]
    fMRI measuring brain activation associated with performance of SIRT


Secondary Outcome Measures :
  1. Neurobehavioral Symptom Inventory [ Time Frame: 12-24 months post-injury ]
    self-report of various domains of emotional status

  2. Post-traumatic Symptom Checklist-Civilian (PCL-C) [ Time Frame: 12-24 months post-injury ]
    Checklist of posttraumatic stress symptoms

  3. Center for the Epidemiological Center for Study of Depression (CES-D) [ Time Frame: 12-24 months post-injury ]
    Self-report measure of depression

  4. Symbol Digit Modalities Test (SDMT) [ Time Frame: 12-24 months post-injury ]
    Measure of processing speed

  5. Trail Making Test A and B [ Time Frame: 12-24 months post-injury ]
    Measure of visuoperceptive performance and speed

  6. Controlled Oral Word Association [ Time Frame: 12-24 months post-injury ]
    Measure of verbal fluency

  7. California Verbal Learning Test 2 [ Time Frame: 12-24 months post-injury ]
    Verbal learning test


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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).
Criteria

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)

Contacts and Locations

Sponsors and Collaborators
Baylor College of Medicine
The Cleveland Clinic
Investigators
Layout table for investigator information
Principal Investigator: Harvey Levin, PhD Baylor College of Medicine
Principal Investigator: Steven Rao, PhD The Cleveland Clinic
Tracking Information
First Submitted Date March 19, 2015
First Posted Date July 9, 2019
Last Update Posted Date July 9, 2019
Study Start Date June 2012
Actual Primary Completion Date May 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: July 8, 2019)
  • 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
  • Brain activation on Sternberg Item Recognition Task (SIRT) [ Time Frame: 12-24 months post-injury ]
    fMRI measuring brain activation associated with performance of SIRT
Original Primary Outcome Measures Same as current
Change History No Changes Posted
Current Secondary Outcome Measures
 (submitted: July 8, 2019)
  • Neurobehavioral Symptom Inventory [ Time Frame: 12-24 months post-injury ]
    self-report of various domains of emotional status
  • Post-traumatic Symptom Checklist-Civilian (PCL-C) [ Time Frame: 12-24 months post-injury ]
    Checklist of posttraumatic stress symptoms
  • Center for the Epidemiological Center for Study of Depression (CES-D) [ Time Frame: 12-24 months post-injury ]
    Self-report measure of depression
  • Symbol Digit Modalities Test (SDMT) [ Time Frame: 12-24 months post-injury ]
    Measure of processing speed
  • Trail Making Test A and B [ Time Frame: 12-24 months post-injury ]
    Measure of visuoperceptive performance and speed
  • Controlled Oral Word Association [ Time Frame: 12-24 months post-injury ]
    Measure of verbal fluency
  • California Verbal Learning Test 2 [ Time Frame: 12-24 months post-injury ]
    Verbal learning test
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Neural and Behavioral Sequelae of Blast-Related Traumatic Brain Injury
Official Title Neural and Behavioral Sequelae of Blast-Related Traumatic Brain Injury
Brief Summary

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.

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
Study Design Observational Model: Case-Control
Time Perspective: Other
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
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).
Condition TBI
Intervention Not Provided
Study Groups/Cohorts Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: July 8, 2019)
60
Original Actual Enrollment Same as current
Actual Study Completion Date May 2014
Actual Primary Completion Date May 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria

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)

Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers Yes
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number NCT04012463
Other Study ID Numbers PT074924P1
PT074924P1
H-22852 ( Other Identifier: Baylor College of Medicine )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Harvey Levin, Baylor College of Medicine
Study Sponsor Baylor College of Medicine
Collaborators The Cleveland Clinic
Investigators
Principal Investigator: Harvey Levin, PhD Baylor College of Medicine
Principal Investigator: Steven Rao, PhD The Cleveland Clinic
PRS Account Baylor College of Medicine
Verification Date March 2015