Clinical trial NCT05823766: Transforming Research and Clinical Knowledge in Traumatic Brain Injury Epileptogenesis Project (TRACK-TBI EPI)
Official title: Transforming Research and Clinical Knowledge in Traumatic Brain Injury Epileptogenesis Project (TRACK-TBI EPI)
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Traumatic Brain Injury
Post-traumatic Epilepsy
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
First posted: 2023-04-21
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants enrolled in TRACK-TBI who screen positive for PTE or participants enrolled in TED Friend Controls cohort

Brief summary: The overarching goal of this study is to improve understanding of the long-range natural history of TBI and post-traumatic epilepsy (PTE) by extending follow-up of a previously enrolled cohort (TRACK-TBI) beyond the first 12 months after injury.

Detailed description: This longitudinal observational study is part of the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) initiative, a multi-institutional project designed to characterize the acute and longer-term clinical, neuroimaging, and blood biomarker features of TBI. TRACK-TBI enrolled TBI patients at 18 Level 1 Trauma Centers in the US, across the age and injury spectrum. This study will extend the follow-up period for TRACK-TBI participants. The extensive clinical, imaging, and biomarker data that has already been collected in these TRACK-TBI participants, in combination with the extended longitudinal data, will allow for the identification of risk factors, co-morbidities, and prognostic biomarkers of TBI. Consequently, the extension of study follow-up will help to determine negative neurological and psychological outcomes of individuals who experienced a TBI compared to healthy and orthopedic controls.

The TRACK-EPI project aims to address the gaps in the existing literature and in the TRACK project regarding PTE. Post-traumatic epilepsy (PTE) is a common complication of traumatic brain injury (TBI), occurring in up to 20% of civilian patients and as many as 50% of military service members who suffer severe brain trauma, and 3-5% of those who suffer moderate TBI. Epilepsy resulting from brain trauma is often difficult to control with medical therapy, and is the cause of epilepsy in approximately 5% of patients referred to specialized epilepsy centers. PTE can be the result of TBI of any severity, although the risk is higher from severe TBI. PTE can arise through a variety of mechanisms, which may co-exist within a single patient. Focal brain injury, which results from penetrating trauma or focal contusions can result in epileptogenesis. Closed head injury can also produce diffuse injury, with shearing of axons and blood vessels, diffuse edema and ischemia, and secondary cellular damage through the release of inflammatory mediators. The clinical features of epilepsy, such as the frequency and severity of seizures, prevalence of associated co-morbidities, and responsiveness to therapy, may differ among these diverse mechanisms. Additionally, the neurophysiologic and imaging features of epileptogenicity also likely differ. Given the frequency of PTE, a more complete understanding of PTE etiology and prognosis is vital. Furthermore, it is likely that a sophisticated understanding of the subtypes of epilepsy resulting from brain trauma will be required to successfully develop anti-epileptogenic therapies.

Eligibility criteria: Inclusion Criteria:

Cohort TBI subjects with PTE

1. Participation in TRACK-TBI Observational Study (Penn IRB # 825503 or local IRB) and/or Spreading Depolarizations II (SDII) (Penn IRB # 828395 or local IRB) who are at least two years post-injury and completed at least 1 GOSE during the TRACK-TBI follow-up assessments
2. Must complete at least one Telephone Assessment (and a recruitment phone call)
3. Endorsed any one of four post-traumatic epilepsy (PTE) items from the Patient Interview at the 6 month or later TRACK-TBI follow-up assessment, and did not have a diagnosis of epilepsy prior to the index TBI
4. Ability of participant or legally authorized representative to provide informed consent Cohort Orthopedic Controls

1. Participation in TRACK-TBI Observational Study (Penn IRB # 825503 or local IRB) and/or Spreading Depolarizations II (SDII) (Penn IRB # 828395 or local IRB) who are at least two years post-injury and completed at least 1 GOSE during the TRACK-TBI follow-up assessments 2. Must complete at least one Telephone Assessment (and a recruitment phone call) 3. Endorsed any one of four post-traumatic epilepsy (PTE) items from the Patient Interview at the 6 month or later TRACK-TBI follow-up assessment, and did not have a diagnosis of epilepsy prior to the index TBI 4. Ability of participant or legally authorized representative to provide informed consent 5. Initial TRACK-TBI orthopedic injury Cohort Friend Controls

1. Participation in TRACK-TBI Observational Study (Penn IRB # 825503 or local IRB) who are at least two years post-enrollment and completed at least 1 MRI during the TRACK-TBI follow-up assessments
2. Ability of participant or legally authorized representative to provide informed consent Participation in TED: Friend Controls Study (IRB # 827537)

Exclusion Criteria:

1. Epilepsy diagnosed prior to index TBI

Primary outcomes:
measure: Glasgow Outcome Scale Extended (GOSE)
timeFrame: 4-6 years after TRACK-TBI enrollment
measure: Diagnostic Interview for Seizure Classification Outside of Video EEG Recording (DISCOVER)
timeFrame: 4-6 years after TRACK-TBI enrollment
Secondary outcomes:
measure: Serum NF-L (neurofilament light chain)
timeFrame: 4-6 years after TRACK-TBI enrollment
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Charlestown
country: United States
facility: Spaulding Rehabilitation Hospital
state: Massachusetts
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania/Penn Presbyterian Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Austin
country: United States
facility: University of Texas at Austin
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
References: