Spreading Depolarizations in Traumatic Brain Injury

• Conditions: Traumatic Brain Injury

• Registration Number: NCT03379220
• Lead Sponsor: 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.

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.

Study Timeline

• Study Start: 2017-03-28
• Status Verified: 2017-12
• Study First Submitted: 2017-12-14
• Study First Submitted QC: 2017-12-14
• Last Update Submitted: 2017-12-19
• Study First Posted: 2017-12-20
• Last Update Posted: 2017-12-21
• Primary Completion: 2019-12-31
• Study Completion: 2020-07-14

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 189

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Glasgow Outcome Scale Extended (GOS-E)	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).

Trial Locations

Locations (7)

University of Miami; 🇺🇸 Miami, Florida, United States

University of Cincinnati; 🇺🇸 Cincinnati, Ohio, United States

Baylor College of Medicine; 🇺🇸 Houston, Texas, United States

University of California San Francisco; 🇺🇸 San Francisco, California, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

University of Pittsburgh; 🇺🇸 Pittsburgh, Pennsylvania, United States