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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03999164
Recruitment Status : Not yet recruiting
First Posted : June 26, 2019
Last Update Posted : November 22, 2019
Sponsor:
Information provided by (Responsible Party):
University of California, Davis

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.

Condition or disease Intervention/treatment Phase
Epilepsy, Post-Traumatic Drug: [18F]DPA-714 Positron Emission Tomography Scan Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Imaging of Glial Activation and Risk for Post-Traumatic Epilepsy
Estimated Study Start Date : January 1, 2020
Estimated Primary Completion Date : August 14, 2022
Estimated Study Completion Date : August 14, 2022


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.




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

Secondary Outcome Measures :
  1. Frequency of early seizures, epileptiform discharges, and post-traumatic epilepsy [ Time Frame: Admission - two years ]
  2. Modified Rankin Scale [ Time Frame: 3 and 6 months ]
    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. Quantify the association between contusion volume and adjacent cerebral edema with [18F]DPA-714 binding on PET scans [ Time Frame: 2 weeks ]
    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



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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03999164


Contacts
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Contact: Ryan M Martin, MD 9167343650 rymartin@ucdavis.edu

Sponsors and Collaborators
University of California, Davis

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Responsible Party: University of California, Davis
ClinicalTrials.gov Identifier: NCT03999164    
Other Study ID Numbers: v1
First Posted: June 26, 2019    Key Record Dates
Last Update Posted: November 22, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of California, Davis:
neuroinflammation
activated microglia
TSPO
Traumatic Brain Injury
TBI
Positron emission tomography
Additional relevant MeSH terms:
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Epilepsy
Epilepsy, Post-Traumatic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Brain Injuries
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries