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

Imaging of Glial Activation and Risk for Post-Traumatic Epilepsy

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Epilepsy, Post-Traumatic
• Intervention / Treatment: Drug: [18F]DPA-714 Positron Emission Tomography Scan

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95817
      • University of California, Davis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 96 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: [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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Quantification of [18F]DPA-714 binding in the brain following moderate to severe traumatic brain injury	2 weeks
Quantification of [18F]DPA-714 binding in the brain following moderate to severe traumatic brain injury	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of early seizures, epileptiform discharges, and post-traumatic epilepsy		Admission - two years
Modified Rankin Scale	All patients will undergo a phone survey at 3 and 6 months post-injury to assess functional outcome using the Modified Rankin Scale. The Modified Rankin Scale measures the degree of disability or dependence in daily activities of patients who have suffered an neurological injury, ranging from 0 (no symptoms) to 6 (dead).	3 and 6 months
Quantify the association between contusion volume and adjacent cerebral edema with [18F]DPA-714 binding on PET scans	All patients will undergo multi-modal MRI brain (Fluid-attenuated inversion recovery (FLAIR), susceptibility weighted imaging(SWI), diffusion weighted imaging(DWI)) two weeks post-injury to assess for acute structural abnormalities	2 weeks

Collaborators and Investigators

• Sponsor: University of California, Davis

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2020
• Primary Completion (Actual): August 14, 2025
• Study Completion (Estimated): August 14, 2026

Study Registration Dates

• First Submitted: June 24, 2019
• First Submitted That Met QC Criteria: June 25, 2019
• First Posted (Actual): June 26, 2019

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: TBI; Traumatic Brain Injury; Positron emission tomography; neuroinflammation; activated microglia; TSPO
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Pathologic Processes; Inflammation; Epilepsy; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Pathological Conditions, Signs and Symptoms; Brain Injuries, Traumatic; Neuroinflammatory Diseases; Epilepsy, Post-Traumatic
• Other Study ID Numbers: 1437948

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No