Clinical trial NCT03379220: Spreading Depolarizations in Traumatic Brain Injury
Official title: Development and Validation of Spreading Depolarization Monitoring for TBI Management
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Traumatic Brain Injury
Lead sponsor: University of Cincinnati
Sponsor class: OTHER
Collaborators: name: U.S. Army Medical Research and Development Command
First posted: 2017-12-20
Enrollment: 189
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Glasgow Outcome Scale Extended (GOS-E)
timeFrame: 6 months following injury
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
Study officials:
References: