Antiseizure Medication for Severe Brain Injury

EG
VL
Overseen ByVarina L Boerwinkle, MD
Age: Any Age
Sex: Any
Trial Phase: Phase 4
Sponsor: University of North Carolina, Chapel Hill
Must be taking: Antiseizure medications
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how antiseizure medications affect brain activity in patients with severe brain injuries and impaired consciousness. Researchers seek to determine if these medications can alter the brain's seizure networks, which might cause seizures, using special brain scans called rs-fMRI. Patients in the ICU who have recently suffered a severe brain injury, such as a stroke or trauma, might be suitable candidates. Participants will take two antiseizure drugs, including Lacosamide Injectable Product (Vimpat) and Levetiracetam, and undergo brain scans before and after to check for changes. As a Phase 4 trial, this research involves FDA-approved treatments and aims to understand how they can benefit more patients.

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop your current medications. However, if you have known allergies or contraindications to the trial's antiseizure medications, you may not be eligible to participate.

What is the safety track record for these treatments?

A previous study found lacosamide safe for treating seizures, even after traumatic brain injury, without harming cognitive skills. Research suggests it may protect the brain if administered before oxygen loss, as demonstrated in studies with newborn rats.

Levetiracetam, another seizure medication, is often used for traumatic brain injuries. It is safe, commonly used in trauma centers to prevent seizures, and performs well compared to similar drugs.

Phenobarbital is recommended for managing brain injuries, particularly to reduce intracranial pressure. It can be used without worsening confusion and may decrease the need for other sedatives.

Phosphenytoin effectively prevents early seizures after traumatic brain injury, especially in adults. Studies show it reduces the risk of seizures soon after the injury.

Valproate sodium may help protect the brain post-injury by reducing brain cell damage and aiding recovery. However, rare cases of nerve damage have occurred, necessitating careful monitoring.

All these medications are FDA-approved for other uses, indicating they are generally well-tolerated. However, like any medication, side effects can occur, so participants are closely monitored during trials.12345

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments because they explore various antiseizure medications to manage seizures after severe brain injury. Unlike some standard treatments, such as carbamazepine or topiramate, which have been commonly used for seizures, this trial includes drugs like lacosamide and levetiracetam, each with unique mechanisms of action. Lacosamide, for instance, stabilizes neuronal membranes by enhancing the slow inactivation of sodium channels, offering a potentially different approach to controlling post-injury seizures. Additionally, the injectable formulations of these treatments allow for rapid administration, which is crucial in acute care settings. This trial aims to determine the effectiveness of these drugs in a specific subgroup of patients, helping to refine and optimize treatment strategies for better outcomes.

What evidence suggests that this trial's antiseizure medications could be effective for severe brain injury?

Research shows that these FDA-approved seizure medications can help reduce seizures in people with brain injuries. In this trial, participants in the Seizure Network Positive group will receive two of these medications. Lab studies have found that lacosamide may protect brain cells after an injury. Levetiracetam is considered safe and works like phenytoin to prevent seizures soon after a brain injury. Phenobarbital can decrease pressure inside the skull, which may help after severe injuries, but it might also cause changes in blood pressure. Fosphenytoin is similar to levetiracetam in preventing seizures, especially in young children with brain injuries. Lastly, valproate sodium can lower the risk of early seizures after a severe brain injury and might help protect the brain from further harm. Studies support these treatments, showing their effectiveness in managing seizures after brain injuries.24678

Who Is on the Research Team?

EG

Emilio G. Cediel, MD

Principal Investigator

UNC-Chapel Hill

VL

Varina L Boerwinkle, MD

Principal Investigator

UNC-Chapel Hill

Are You a Good Fit for This Trial?

This trial is for ICU patients with severe brain injuries from events like stroke or cardiac arrest, who are stable enough for an MRI but have a Glasgow Coma Scale score under 9. They must be within 3 to 45 days of their injury and not allergic to the study drugs, pregnant, brain dead, have contraindications for MRI scans, epilepsy history, or severe neurological dependence.

Inclusion Criteria

Currently ICU hospitalized
I have been diagnosed with an acute brain injury from a trauma or lack of oxygen.
3 to 45 days from acute brain injury to enrollment time by medical chart review
See 2 more

Exclusion Criteria

My doctor says I can't have 2 of the 5 specific treatments in the study.
My medical records show a history of epilepsy.
You are pregnant based on your medical history or a positive pregnancy test.
See 6 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-3 days

Initial Assessment

Participants undergo an initial rs-fMRI to identify seizure networks

1-3 days
1 visit (in-person)

Treatment

Participants with identified seizure networks receive antiseizure medication and undergo a second rs-fMRI

3-13 days
Multiple visits (in-person) for medication administration and assessments

Follow-up

Participants are monitored for changes in seizure networks and typical resting state networks post-treatment

3-13 days
1 visit (in-person) for follow-up assessments

What Are the Treatments Tested in This Trial?

Interventions

  • Lacosamide Injectable Product
  • Levetiracetam
  • Phenobarbital Sodium Injection
  • Phosphenytoin
  • Valproate Sodium
Trial Overview The study tests if FDA-approved antiseizure medications can change how seizure networks in the brain connect after serious injury. Patients' brains are scanned before and after treatment using rs-fMRI to see if there's any difference in these connections.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Active Control
Group I: Seizure network Positive subjectsExperimental Treatment5 Interventions
Group II: Seizure network Negative subjectsActive Control1 Intervention

Lacosamide Injectable Product is already approved in European Union, United States, Canada, Japan for the following indications:

🇪🇺
Approved in European Union as Vimpat for:
🇺🇸
Approved in United States as Vimpat for:
🇨🇦
Approved in Canada as Vimpat for:
🇯🇵
Approved in Japan as Vimpat for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of North Carolina, Chapel Hill

Lead Sponsor

Trials
1,588
Recruited
4,364,000+

Published Research Related to This Trial

Clobazam and rufinamide are effective adjunctive therapies for Lennox-Gastaut syndrome (LGS), with clobazam approved for patients aged 2 years and older and rufinamide for those aged 4 years and older.
Lacosamide and vigabatrin target different seizure types, with lacosamide enhancing sodium channel inactivation for partial onset seizures in patients 17 and older, and vigabatrin used for infantile spasms in very young children and complex partial seizures in adults.
An overview of third-generation antiseizure drugs: Clobazam, lacosamide, rufinamide, and vigabatrin.Spanaki, MV., Barkley, GL.[2020]
In a study involving 132 patients with traumatic brain injury, both valproate and phenytoin were found to have similar low rates of early seizures, indicating that neither drug is superior for this purpose.
Valproate did not show any advantage over short-term phenytoin for preventing late seizures and was associated with a trend toward higher mortality, suggesting it should not be routinely used for posttraumatic seizure prevention.
Valproate therapy for prevention of posttraumatic seizures: a randomized trial.Temkin, NR., Dikmen, SS., Anderson, GD., et al.[2022]
Lacosamide (Vimpat) was approved in August 2008 by the European Commission and in October 2008 by the FDA as an adjunctive therapy for partial-onset seizures in epilepsy patients.
The approval indicates that lacosamide is considered a safe and effective option to help manage seizures when used alongside other treatments.
Lacosamide.Perucca, E., Yasothan, U., Clincke, G., et al.[2018]

Citations

1.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/24636248/
Effect of lacosamide on structural damage and functional ...The present study was designed to assess the profile of a novel anticonvulsant, lacosamide (Vimpat) on post-TBI structural, motor and cognitive ...
Effect of lacosamide on structural damage and functional ...Lacosamide slightly delayed motor recovery during the 2-wk post-TBI follow-up. •. Lacosamide did not compromise cognitive outcome after traumatic brain injury.
Neuroprotective Effect of Lacosamide on Hypoxic-Ischemic ...This study suggests that LCM pretreatment exerts a neuroprotective effect on hypoxia-ischemia in neonatal rats.
A Pilot Study of NSICU Assessment of Seizure Prophylaxis ...Patients with severe traumatic brain injury (TBI) or subarachanoid hemorrhage (SAH) randomized to seizure prophylaxis with either lacosamide. Intervention ...
Abstracts - American Epilepsy SocietyPROSPECTIVE RANDOMIZED SINGLE-BLINDED TRIAL OF LACOSAMIDE VERSUS FOSPHENYTOIN FOR SEIZURE PROPHYLAXIS IN TRAUMATIC BRAIN INJURY ; Abstract number ...
VIMPAT® (lacosamide) - accessdata.fda.govThe safety of a 15-minute loading dose administration of VIMPAT Injection 200 mg to 400 mg followed by oral administration of VIMPAT given twice daily at the ...
Seizure Prevention in Traumatic Brain Injury With ...The purpose of this study is to assess the incidence of early post-traumatic seizures. The study will also assess the benefit of lacosamide compared to ...
LacosamideLacosamide is used to treat focal (partial) seizures in adults and children. To learn more, visit Epilepsy Foundation.
Unbiased ResultsWe believe in providing patients with all the options.
Your Data Stays Your DataWe only share your information with the clinical trials you're trying to access.
Verified Trials OnlyAll of our trials are run by licensed doctors, researchers, and healthcare companies.
Terms of Service·Privacy Policy·Cookies·Security