Spreading Depolarizations in Traumatic Brain Injury

NCT ID: NCT03379220

Last Updated: 2017-12-21

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 189 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-03-28
• Study Completion Date: 2020-07-14

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.

Conditions

Traumatic Brain Injury

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

No interventions assigned to this group

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.

No interventions assigned to this group

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.

No interventions assigned to this group

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

U.S. Army Medical Research and Development Command

FED

Sponsor Role: collaborator

University of Cincinnati

OTHER

Sponsor Role: lead

Responsible Party

Jed Hartings

Research Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of California San Francisco

San Francisco, California, United States

Site Status: RECRUITING

University of Miami

Miami, Florida, United States

Site Status: RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status: NOT_YET_RECRUITING

University of Cincinnati

Cincinnati, Ohio, United States

Site Status: RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status: NOT_YET_RECRUITING

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status: RECRUITING

Baylor College of Medicine

Houston, Texas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Jed Hartings, PhD

Role: CONTACT

Phone: 5135583567

Email: Jed.Hartings@uc.edu

Facility Contacts

Geoff T Manley, MD

Role: primary

Kristine H O'Phelan, MD

Role: primary

Eric S Rosenthal, MD

Role: primary

Laura B Ngwenya, MD, PhD

Role: primary

Ramani Balu, MD, PhD

Role: primary

David O Okonkwo, MD, PhD

Role: primary

Shankar P Gopinath, MD

Role: primary

Other Identifiers

Hartings SD-II

Identifier Type: -

Identifier Source: org_study_id