PET Brain Imaging for Post-Traumatic Epilepsy

Overseen By Ryan M Martin, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of California, Davis

Disqualifiers: Pregnancy, Neurodegenerative disorders, Epilepsy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

30 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment [18F]DPA-714 Positron Emission Tomography Scan for epilepsy?

PET scans, including those using different tracers, are effective in identifying areas of the brain involved in epilepsy, which can help in planning surgical treatments. This imaging technique is valuable for locating the seizure onset zone, improving surgical outcomes for patients with epilepsy. ^{1 2 3 4 5}

Is [18F]DPA-714 PET imaging safe for humans?

There is no specific safety data for [18F]DPA-714 PET imaging in humans, but studies in animal models have used it to monitor brain inflammation without reporting safety concerns. ^{4 6 7 8 9}

How does PET brain imaging differ from other treatments for post-traumatic epilepsy?

PET brain imaging is unique because it uses a special type of scan to identify the specific areas of the brain involved in seizures, which can help in planning surgery or other targeted treatments. Unlike standard treatments that focus on controlling symptoms, PET imaging provides detailed information about brain activity and metabolism, offering a more precise approach to managing epilepsy. ^{3 4 10 11 12}

Eligibility Criteria

This trial is for adults aged 18-100 who've had a moderate to severe traumatic brain injury. They should be enrolled within 72 hours of the injury and have specific types of brain damage. People with pre-existing neurological conditions, pregnancy, or metal implants that prevent MRI scans can't participate.

Inclusion Criteria

I have recently suffered a traumatic brain injury.

I am partially conscious without needing constant sedation.

Patients with multiple injuries, such as broken bones, abdominal injuries or other similar injuries, will be allowed to participate.

Exclusion Criteria

You have a pre-existing disorder that affects your brain and nervous system.

You are pregnant.

I have suffered a brain injury due to lack of oxygen.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants undergo PET scans of the brain at two weeks and two months after injury to measure neuro-inflammation

2 months

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including phone surveys at 3 and 6 months post-injury

6 months

2 visits (phone)

Treatment Details

Interventions

• [18F]DPA-714 Positron Emission Tomography Scan

Trial Overview [18F]DPA-714 PET scans are being used to track brain inflammation after a traumatic injury at two weeks and two months post-injury. The study aims to link the level of inflammation detected with the risk of developing post-traumatic epilepsy.

Participant Groups

Group I: Moderate to Severe Traumatic Brain Injury Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

University of California, Davis

Lead Sponsor

Trials

958

Recruited

4,816,000+

Findings from Research

Functional neuroimaging techniques, such as positron and single photon emitter-labeling, have significantly advanced our understanding of seizure activity and related brain dysfunctions in epilepsy, providing insights that other methods cannot offer.

There is a need for the development of new radiotracers to study specific receptors involved in epilepsy, which could enhance our understanding of seizure mechanisms and the effects of antiepileptic treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuropharmacological imaging in epilepsy with PET and SPECT. Henry, TR., Pennell, PB.[2016]

Nuclear medicine techniques like SPECT and PET are crucial for accurately locating the seizure onset zone in patients with refractory epilepsy, which is essential for successful surgical outcomes.

Ictal perfusion SPECT imaging is particularly effective in detecting seizure onset zones, especially in temporal lobe epilepsy, while interictal FDG-PET can identify areas of hypometabolism that may extend beyond the seizure onset zone, highlighting the importance of advanced imaging techniques in epilepsy management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuronuclear assessment of patients with epilepsy. Goffin, K., Dedeurwaerdere, S., Van Laere, K., et al.[2016]

Positron emission tomography (PET) using FDG is highly effective in localizing seizure foci in patients with intractable temporal lobe epilepsy (TLE), showing unilateral temporal lobe hypometabolism in 86% of cases, compared to 76% for MRI.

PET findings, particularly unilateral temporal lobe hypometabolism, are strong predictors of positive surgical outcomes, with 86% of patients experiencing good results after temporal lobectomy when hypometabolism is present.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Positron emission tomography and epilepsy. Casse, R., Rowe, CC., Newton, M., et al.[2019]

Neuroimaging techniques, particularly positron emission tomography (PET) with 18F-FDG, are crucial for accurately locating epileptogenic zones in patients with epilepsy, aiding in presurgical evaluations.

The development of various receptor ligands for PET studies, such as those targeting benzodiazepine and glutamate receptors, enhances the ability to assess and treat epilepsy more effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Diagnosis of epilepsy by PET scan]. Kumlien, E.[2008]

Functional brain imaging techniques like SPECT and PET are now crucial for diagnosing and evaluating epilepsy, offering localization capabilities similar to traditional EEG methods but with fewer interpretation challenges.

SPECT imaging, in particular, has become dominant in assessing seizure activity, providing valuable insights into brain perfusion and metabolism that can inform treatment decisions and improve management of epilepsy, including in pediatric cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single photon emission computed tomography in epilepsy. Devous, MD., Leroy, RF., Homan, RW.[2019]

In a study of 27 children with intractable focal epilepsy, 85.1% showed increased uptake of the neuroinflammation marker [11C] DPA713 in their epileptic lesions, indicating its potential as a sensitive tool for identifying epileptic foci.

The study found that increased [11C] DPA713 uptake correlated with microglial activation in patients who underwent surgery, suggesting that neuroinflammation plays a significant role in the pathophysiology of focal epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical evaluation of neuroinflammation in child-onset focal epilepsy: a translocator protein PET study. Kagitani-Shimono, K., Kato, H., Kuwayama, R., et al.[2021]

Four new analogues of DPA-714 were developed, showing improved affinity and selectivity for the TSPO receptor compared to the original compound, indicating potential for enhanced therapeutic effects.

The selected analogue, DPA-C5yne, demonstrated favorable metabolic stability and was successfully labeled with fluorine-18 for PET imaging, suggesting its utility in studying neuroinflammation in vivo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preparation and evaluation of novel pyrazolo[1,5-a]pyrimidine acetamides, closely related to DPA-714, as potent ligands for imaging the TSPO 18kDa with PET. Médran-Navarrete, V., Damont, A., Peyronneau, MA., et al.[2016]

Using PET imaging with the (18)F-labeled DPA-714 ligand, researchers successfully monitored the inflammatory response in a rat model of traumatic brain injury (TBI), showing significant increases in microglial activation in the injured brain area compared to controls.

The study demonstrated that TSPO-targeted PET imaging can effectively track the temporal changes in neuroinflammation after TBI, peaking around day 6 post-injury, which could aid in understanding and developing anti-inflammatory therapies for TBI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PET imaging of neuroinflammation in a rat traumatic brain injury model with radiolabeled TSPO ligand DPA-714. Wang, Y., Yue, X., Kiesewetter, DO., et al.[2022]

In a mouse model of stroke, treatment with AMD3100 significantly reduced neuroinflammation, as indicated by decreased TSPO levels measured through PET imaging, suggesting its potential as an anti-inflammatory therapy.

The study utilized a combination of in vivo PET scans and ex vivo histological analysis to confirm the effectiveness of AMD3100 in reducing inflammation, demonstrating the utility of TSPO-targeted imaging in evaluating treatment efficacy after ischemic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[(18)F]DPA-714 PET imaging of AMD3100 treatment in a mouse model of stroke. Wang, Y., Yue, X., Kiesewetter, DO., et al.[2021]

Recent advancements in neuroimaging techniques for epilepsy, such as MRI, PET, and SPECT, have significantly improved the detection of brain lesions and metabolic patterns associated with seizures.

Ictal SPECT has emerged as a valuable tool for accurately localizing seizures, enhancing the overall diagnostic capabilities in epilepsy management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging in epilepsy. Cook, MJ., Kilpatrick, C.[2019]

Functional neuroimaging techniques like PET and SPECT provide critical information for managing epilepsy that MRI alone cannot, particularly in identifying epileptogenic versus nonepileptogenic lesions.

The use of specific PET tracers, such as FDG and FMZ, has shown promise in evaluating drug-resistant epilepsy, especially in children, highlighting the need for effective seizure control to support cognitive development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional neuroimaging in the preoperative evaluation of children with drug-resistant epilepsy. Sood, S., Chugani, HT.[2019]

In a study involving 7 patients with refractory temporal lobe epilepsy and 2 healthy controls, PET imaging using both FDG and FFMZ successfully identified abnormal brain regions, demonstrating its utility in localizing seizure onset zones (SOZ).

The lateralization of SOZ findings from PET imaging matched SEEG data in 86% of cases for FFMZ and 71% for FDG, indicating that quantitative PET imaging is a reliable complementary tool for presurgical evaluation of epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative Analysis of [18F]FFMZ and [18F]FDG PET Studies in the Localization of Seizure Onset Zone in Drug-Resistant Temporal Lobe Epilepsy. Avendaño-Estrada, A., Velasco, F., Velasco, AL., et al.[2020]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Neuropharmacological imaging in epilepsy with PET and SPECT. [2016]

2. United States pubmed.ncbi.nlm.nih.gov

Neuronuclear assessment of patients with epilepsy. [2016]

3. United States pubmed.ncbi.nlm.nih.gov

Positron emission tomography and epilepsy. [2019]

4. Sweden pubmed.ncbi.nlm.nih.gov

[Diagnosis of epilepsy by PET scan]. [2008]

5. United States pubmed.ncbi.nlm.nih.gov

Single photon emission computed tomography in epilepsy. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Clinical evaluation of neuroinflammation in child-onset focal epilepsy: a translocator protein PET study. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Preparation and evaluation of novel pyrazolo[1,5-a]pyrimidine acetamides, closely related to DPA-714, as potent ligands for imaging the TSPO 18kDa with PET. [2016]

8. Germany pubmed.ncbi.nlm.nih.gov

PET imaging of neuroinflammation in a rat traumatic brain injury model with radiolabeled TSPO ligand DPA-714. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

[(18)F]DPA-714 PET imaging of AMD3100 treatment in a mouse model of stroke. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Imaging in epilepsy. [2019]

11. Germany pubmed.ncbi.nlm.nih.gov

Functional neuroimaging in the preoperative evaluation of children with drug-resistant epilepsy. [2019]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Quantitative Analysis of [18F]FFMZ and [18F]FDG PET Studies in the Localization of Seizure Onset Zone in Drug-Resistant Temporal Lobe Epilepsy. [2020]