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Spreading Depolarizations in Traumatic Brain Injury

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03379220
Recruitment Status : Recruiting
First Posted : December 20, 2017
Last Update Posted : December 21, 2017
U.S. Army Medical Research and Development Command
Information provided by (Responsible Party):
Jed Hartings, University of Cincinnati

Brief Summary:
This research aims to extend the application of spreading depolarization monitoring to non-surgical TBI patients, using intraparenchymal electrode arrays and scalp electroencephalography to detect depolarizations and develop less invasive monitoring methods.

Condition or disease
Traumatic Brain Injury

Detailed Description:
This study aims to develop the new clinical science of spreading depolarizations for routine monitoring of all TBI patients requiring intensive care. This will be accomplished by investigating automated and non-invasive methods for bedside detection of spreading depolarizations and by determining the prognostic value of such monitoring across the spectrum of TBI severity. While current monitoring of depolarizations is invasive and limited to the subgroup of TBI patients requiring craniotomy, pilot studies have shown that spreading depolarizations are also manifested in non-invasive scalp electroencephalographic (EEG) recordings. Here, approximately 189 subjects will undergo neuromonitoring with EEG only (n=63), with combined EEG and intraparenchymal ECoG (n=63), or with combined EEG and subdural ECoG (n=63). Simultaneous ECoG and EEG monitoring will allow characterization of the EEG signatures of spreading depolarizations and enable identification of signal-processing steps and quantitative criteria for their detection with clinically meaningful sensitivity and specificity, as validated against the gold standard of invasive ECoG. In parallel, an observational electrophysiology study of all TBI patients admitted to intensive care, including non-surgical cases, will characterize the incidence of spreading depolarizations across the TBI severity spectrum. Successful completion of these objectives will 1) determine the extent to which findings obtained in surgical TBI patients also generalize to patients who are managed medically, and 2) establish the first non-invasive method for routine bedside monitoring of a neuronal pathomechanism with proven relevance to TBI outcome. In doing so, this study may enable an individualized approach to TBI management and clinical trials in which neuroprotective therapies can be administered selectively to patients based on real-time identification of a marker and mechanism of secondary neuronal injury.

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Study Type : Observational
Estimated Enrollment : 189 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Development and Validation of Spreading Depolarization Monitoring for TBI Management
Actual Study Start Date : March 28, 2017
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : July 14, 2020

Resource links provided by the National Library of Medicine

Subdural ECoG (Group 1)
For patients who require craniotomy to treat TBI, a subdural electrode strip will be placed intraoperatively following evacuation of a hematoma or contusion, as required. Electrode strips will be used for subsequent electrocorticography (ECoG) during intensive care. Patients will also undergo continuous scalp EEG monitoring.
Burr Hole ECoG (Group 2)
For patients who do not require surgery but do require invasive monitoring, an intraparenchymal ECoG electrode array will be placed through a cranial burr hole. Depending on other monitoring needs, the location of injuries, and other clinical considerations, the burr hole may be the same as used for placement of other probes or may be separate. In cases of focal injury, the burr hole will be placed to allow electrode targeting to a lobe with significant primary lesion(s). Patients will also undergo continuous scalp EEG monitoring.
EEG (Groups 1-3)
Continuous EEG recordings will be made using Ag/AgCl electrodes placed on or beneath the scalp (subdermal wire) according to standard practice. The default montage will employ eight lead electrodes for each hemisphere following the 10/20 system (Right: Fp2, F4, C4, P4, O2, F8, T4, T6; left: Fp1, F3, C3, P3, O1, F7, T3, T5). Other montages with more dense placement of electrodes in the region of ECoG monitoring may also be used.

Primary Outcome Measures :
  1. Glasgow Outcome Scale Extended (GOS-E) [ Time Frame: 6 months following injury ]
    Glasgow Outcome Scale- Extended (GOS-E) is an ordinal global scale for functional outcome that rates patient status into one of eight categories, with higher scores representing better recovery: Dead (1), Vegetative State (2), Lower Severe Disability (3), Upper Severe Disability (4), Lower Moderate Disability (5), Upper Moderate Disability (6), Lower Good Recovery (7), and Upper Good Recovery (8).

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Approximately 189 patients admitted to intensive care for treatment of TBI will be enrolled. The study will be conducted as an addition to TRACK-TBI (Transforming Research and Clinical Knowledge in Traumatic Brain Injury), an observational study conducted at 11 sites in the United States. The present study will be implemented at 7 of the 11 sites: University of Cincinnati, University of Pennsylvania, University of Pittsburgh, University of Miami, Massachusetts General Hospital, University of California San Francisco, and Baylor College of Medicine.

Inclusion Criteria:

  1. Enrollment in TRACK-TBI CA cohort
  2. Admission to intensive care
  3. Documented TBI <24 hr before anticipated placement of electrodes
  4. Lobe of primary injury accessible for ECoG by burr hole or craniotomy access
  5. Age ≥ 18 years
  6. Acute brain CT for clinical care
  7. Visual acuity/hearing adequate for testing
  8. Fluency in English or Spanish
  9. Ability to obtain informed consent

Exclusion Criteria:

  1. Significant polytrauma that would confound outcome assessment
  2. Prisoners or patients in custody
  3. Pregnancy
  4. Patients on psychiatric hold
  5. Major debilitating baseline mental health disorder that would interfere with follow-up and the validity of outcome
  6. Major debilitating neurological disease impairing baseline awareness, cognition, or validity of follow-up and outcome assessment
  7. Significant history of pre-existing conditions that would interfere with follow-up and outcome assessment
  8. Low likelihood of follow-up
  9. Current participation in an interventional trial
  10. Penetrating TBI
  11. Spinal cord injury with ASIA score of C or worse
  12. Bilateral unreactive pupils or other evidence of unsurvivable injury
  13. Evidence of coagulopathy (INR>1.5 or thrombocytopenia) or infection, which contraindicate invasive monitoring

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03379220

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Contact: Jed Hartings, PhD 5135583567

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United States, California
University of California San Francisco Recruiting
San Francisco, California, United States, 94110
Contact: Geoff T Manley, MD   
United States, Florida
University of Miami Recruiting
Miami, Florida, United States, 33136
Contact: Kristine H O'Phelan, MD   
United States, Massachusetts
Massachusetts General Hospital Not yet recruiting
Boston, Massachusetts, United States, 02114
Contact: Eric S Rosenthal, MD   
United States, Ohio
University of Cincinnati Recruiting
Cincinnati, Ohio, United States, 45267
Contact: Laura B Ngwenya, MD, PhD   
United States, Pennsylvania
University of Pennsylvania Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Ramani Balu, MD, PhD   
University of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: David O Okonkwo, MD, PhD   
United States, Texas
Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Contact: Shankar P Gopinath, MD   
Sponsors and Collaborators
University of Cincinnati
U.S. Army Medical Research and Development Command

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Responsible Party: Jed Hartings, Research Associate Professor, University of Cincinnati Identifier: NCT03379220     History of Changes
Other Study ID Numbers: Hartings SD-II
First Posted: December 20, 2017    Key Record Dates
Last Update Posted: December 21, 2017
Last Verified: December 2017

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Brain Injuries
Brain Injuries, Traumatic
Wounds and Injuries
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System