Transforming Research and Clinical Knowledge in Traumatic Brain Injury Epileptogenesis Project (TRACK-TBI EPI)

Traumatic Brain Injury Clinical Trial

Official title:

Transforming Research and Clinical Knowledge in Traumatic Brain Injury Epileptogenesis Project (TRACK-TBI EPI)

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05823766
• Other study ID #: 834420
• Status: Enrolling by invitation
• Start date: March 1, 2022
• Est. completion date: February 2027

Study information

• Verified date: April 2024
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 300
• Est. completion date: February 2027
• Est. primary completion date: February 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Brain Injuries
• Brain Injuries, Traumatic
• Epilepsy, Post-Traumatic
• Post-traumatic Epilepsy
• Traumatic Brain Injury
• Wounds and Injuries

Intervention

Behavioral:
• In-Person Outcome Assessment
Assessments will be administered to evaluate participant outcome status

Procedure:
• 3T Magnetic Resonance Imaging (MRI)
Participants will be asked to complete a 3T MRI

Behavioral:
• Clinical Visit
Patients who screen positive for PTE will have an in-depth clinical visit

Procedure:
• Blood Draw
Blood Draw for Plasma, DNA, Serum, RNA
• EEG
An EEG will be performed on patients who screen positive for PTE at the clinical visit

Behavioral:
• Telephone Outcome Assessment
Assessments will be administered over the telephone to evaluate participant outcome status and screen for PTE

Locations

Country	Name	City	State
United States	University of Texas at Austin	Austin	Texas
United States	Spaulding Rehabilitation Hospital	Charlestown	Massachusetts
United States	University of Cincinnati	Cincinnati	Ohio
United States	University of Texas Southwestern	Dallas	Texas
United States	Baylor College of Medicine	Houston	Texas
United States	University of Pennsylvania/Penn Presbyterian Medical Center	Philadelphia	Pennsylvania
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	University of California, San Francisco	San Francisco	California
United States	University of Washington	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
University of Pennsylvania	United States Department of Defense

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Glasgow Outcome Scale Extended (GOSE)	The GOSE provides an overall measure of functional status based on information on cognition, independence, employability, and social/community participation collected via structured interview. Individuals are described by one of the eight outcome categories: 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). Good Recovery is defined as a score of 7-8, Moderate Disability is defined by a score of 5-6 and Severe Disability is defined by a score of 3-4.	4-6 years after TRACK-TBI enrollment
Primary	Diagnostic Interview for Seizure Classification Outside of Video EEG Recording (DISCOVER)	During the clinical evaluation, participants and their caregivers are educated about the heterogeneous and protean manifestations of epileptic seizures, and encouraged to contact study staff if seizures or seizure-like events are noted. The DISCOVER form has been found to be highly accurate when compared to gold-standard video-EEG recording in an Epilepsy Monitoring Unit for classifying seizures	4-6 years after TRACK-TBI enrollment
Secondary	Serum NF-L (neurofilament light chain)	Using advanced blood-based assay platforms, levels of blood biomarkers neurofilament light chain (NF-L) will be measured to validate the utility as a biomarkers for traumatic axonal injury (TAI).	4-6 years after TRACK-TBI enrollment