Imaging of Neuro-Inflammation and the Risk for Post-Traumatic Epilepsy

NCT ID: NCT03999164

Last Updated: 2026-01-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-01
• Study Completion Date: 2026-08-14

Brief Summary

This study plans to evaluate the time course of inflammation in the brain after a moderate to severe traumatic brain injury using positron emission tomography (PET) brain imaging. Patients will undergo PET scans of the brain at two weeks and two months after injury to measure neuro-inflammation. The results of the PET scans will be analyzed and correlated with the risk of post-traumatic epilepsy.

Detailed Description

The development of post-traumatic epilepsy (PTE) is associated with neurobiological, cognitive, psychological, and social consequences that are far-reaching for the patient. Despite our keen awareness of this significant public health issue, little is known regarding the biological mechanisms leading to PTE. One plausible mechanism is that unchecked neuroinflammation, a process that occurs in animal and human models of both traumatic brain injury (TBI) and epilepsy, leads to altered synaptic transmission and neuronal excitability. However, the direct relationship between neuroinflammation and PTE has been difficult to ascertain from pre-clinical studies as they may not accurately reflect the human condition, as few animal models can induce the progression of PTE without a pharmacological enhancer and are predominately limited to studies of mild-to-moderate TBI given high animal mortality rates from more severe injuries. Measurements of neuroinflammation in human TBI and epilepsy has also proven difficult without invasive monitoring or post-mortem evaluations, and measurements of inflammatory mediators in blood or serum may not meaningfully reflect the extent of neuroinflammation.

Encouragingly though, positron emission tomography (PET) can be used to measure the degree of in vivo glial activation in the central nervous system through radiotracer binding of the translocator protein (TSPO), serving as a surrogate of neuroinflammation. Minimally expressed in the uninjured brain, TSPO binding is increased in a number of brain disorders associated with neuroinflammation, including Alzheimer's disease, ischemic stroke, recurrent head trauma in football, brain metastases, TBI, and epilepsy, and is expressed predominately by activated microglia, the main mediators of neuroinflammation. Currently, no pre-clinical or clinical study has analyzed the relationship between glia activation, as measured by TSPO PET, and the risk for developing PTE. Accordingly, we plan to use [18F]DPA-714 to characterize neuro-inflammation following moderate-to-severe TBI in order to better understand the temporal time course of neuro-inflammation following injury and its potential role in epileptogenesis.

Conditions

Epilepsy, Post-Traumatic

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Moderate to Severe Traumatic Brain Injury

All patients will undergo a \[18F\]DPA-714 PET scan of the brain 2 weeks and 2 months following moderate to severe traumatic brain injury to quantify neuroinflammation.

Group Type: EXPERIMENTAL

[18F]DPA-714 Positron Emission Tomography Scan

Intervention Type: DRUG

All patients will undergo a \[18F\]DPA-714 PET scan of the brain 2 weeks and 2 months following moderate to severe traumatic brain injury to quantify neuroinflammation.

Interventions

[18F]DPA-714 Positron Emission Tomography Scan

All patients will undergo a \[18F\]DPA-714 PET scan of the brain 2 weeks and 2 months following moderate to severe traumatic brain injury to quantify neuroinflammation.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Acute Traumatic Brain Injury (TBI)
• Age 18-100 are eligible
• Glasgow Coma Scale (GCS) 3-13 without continuous sedation at time of enrollment
• Ability to enroll within 72 hours of injury
• Hemorrhagic contusional injuries to frontal and/or temporal lobes.
• Polytrauma including long bone fractures, blunt trauma, abdominal trauma or similar will be allowed
• Penetrating TBI if continuous electroencephalography (cEEG) is feasible and survival for 2 years is feasible, recognizing that MRI may not be feasible with some forms of penetrating trauma

Exclusion Criteria

• Low-affinity TSPO binding profile
• Ages 17 years or younger
• Patients with diffuse axonal injury in the absence of hemorrhagic contusions or skull fracture, and isolated epidural hemorrhages that improve after evacuation
• No planned continuous EEG monitoring during injury day 1-7
• Inability to undergo MRI at 14 days (± 4 days) due to bullet, metal implant, or pacemaker
• Pregnancy
• Pre-existing Neurodegenerative Disorders
• Pre-existing epilepsy/seizure disorder
• Pre-existing dementia
• Isolated anoxic brain injury
• Incarceration present or pending
• Devastating cervical spine injury

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of California, Davis

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of California, Davis

Sacramento, California, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Ryan M Martin, MD

Role: CONTACT

rymartin@ucdavis.edu

9167343650

Facility Contacts

Ryan Martin, MD

Role: primary

rymartin@ucdavis.edu

916-734-6518

Other Identifiers

1437948

Identifier Type: -

Identifier Source: org_study_id