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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial studies brain inflammation after moderate to severe traumatic brain injury (TBI) using a specialized brain scan called a PET scan ([18F]DPA-714 Positron Emission Tomography Scan). Researchers aim to observe how inflammation changes over time and whether it links to the risk of developing post-traumatic epilepsy. Participants will undergo PET scans at two weeks and two months post-injury. This trial suits individuals who recently experienced a moderate to severe TBI with specific types of brain injuries and can enroll within 72 hours of the injury. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the chance to contribute to this groundbreaking study.

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 prior data suggests that this PET brain imaging is safe for patients with traumatic brain injury?

Research shows that [18F]DPA-714, used in PET scans, is a special substance that helps create images of brain inflammation. This technique has proven helpful in animal studies, but limited information exists about its safety in humans. As this trial is in its early stages, researchers are still assessing the treatment's safety and determining the right dose. Although no specific problems have been reported in humans so far, the limited data indicates that more research is needed to fully understand its safety. Participants should be aware that the safety information is not yet complete. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using the [18F]DPA-714 PET scan for post-traumatic epilepsy because it offers a new way to visualize neuroinflammation in the brain. Unlike traditional treatments that primarily focus on controlling seizures with medications, this imaging technique provides detailed insights into brain inflammation following traumatic brain injury. By targeting neuroinflammation, [18F]DPA-714 PET scans could help personalize treatment strategies and improve our understanding of epilepsy's underlying causes. This approach represents a significant shift from just treating symptoms to potentially addressing one of the root causes of post-traumatic epilepsy.

What evidence suggests that this PET scan is effective for evaluating post-traumatic epilepsy?

Research shows that the [18F]DPA-714 PET scan effectively tracks brain inflammation after injuries. This imaging technique detects inflammation by measuring a specific protein (TSPO) that often increases with brain injury. Studies have successfully used [18F]DPA-714 PET scans to identify brain areas affected by trauma, aiding in understanding the severity and impact of injuries. In this trial, participants with moderate to severe traumatic brain injury will undergo [18F]DPA-714 PET scans of the brain 2 weeks and 2 months after injury to quantify neuroinflammation. Early human tests suggest that [18F]DPA-714 provides clear and stable images, making it a valuable tool for assessing brain inflammation. These findings support its potential use in evaluating the risk of post-traumatic epilepsy by observing changes in the brain over time. ^{2 4 5 6 7}

Are You a Good Fit for This Trial?

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.

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

You are pregnant.

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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 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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10663012/

[18F]DPA-714 PET Imaging in the Presurgical Evaluation of ... This study aims to assess the contributions of TSPO imaging using [ 18 F]DPA-714 PET and [ 18 F]FDG PET for localizing the EZ during presurgical assessment of ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0969805111002459

Initial evaluation in healthy humans of [ 18 F]DPA-714, a ... This initial study in humans shows that [ 18 F]DPA-714 is a promising PET radioligand with excellent in vivo stability and biodistribution, and acceptable ...

3. jneuroinflammation.biomedcentral.com jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-016-0604-9

Combined [18F]DPA-714 micro-positron emission tomography ... [18F]DPA-714 uptake in μPET/autoradiography correlates with trauma severity, brain metabolic deficits, and microglia activation after closed ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35157105/

[ 18 F]DPA-714 PET imaging for the quantitative evaluation ... These results indicate that the early spatiotemporal characteristics of neuroinflammation quantitatively evaluated by [ 18 F]DPA-714 PET imaging provide ...

5. withpower.com withpower.com/trial/phase-1-epilepsy-post-traumatic-1-2020-cfcd3

PET Brain Imaging for Post-Traumatic Epilepsy 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 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03999164

Imaging of Neuro-Inflammation and the Risk for Post- ... 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 ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0969804321004267

An automated radiosynthesis of [ 18 F]DPA-714 on a ... [ 18 F]DPA-714 is a radiotracer specific to the translocator protein (TSPO) and is useful for in vivo Positron Emission Tomography imaging studies.