Antiseizure Medication in Seizure Networks at Early Acute Brain Injury

University of North Carolina (UNC)

Status and phase: Terminated; Phase 4

Conditions: Brain Ischemia; Coma; Heart Arrest; Brain Injuries, Acute; Stroke; Brain Injuries, Traumatic; Intracranial Hemorrhages; Brain Hypoxia; Persistent Vegetative State; Hypoxia-Ischemia, Brain

Treatments: Drug: Lacosamide Injectable Product; Drug: Phenobarbital Sodium Injection; Drug: Valproate Sodium; Drug: Fosphenytoin; Drug: Levetiracetam

Study type: Interventional

Funder types: Other

Identifiers

NCT06081283

23-0157

Details and patient eligibility

About

The goal of this clinical trial is to explore the effect of FDA-approved antiseizure drugs in the brain connectivity patterns of severe and moderate acute brain injury patients with suppression of consciousness. The main questions it aims to answer are:

• Does the antiseizure medication reduce the functional connectivity of seizure networks, as identified by resting state functional MRI (rs-fMRI), within this specific target population?
• What is the prevalence of seizure networks in patients from the target population, both with EEG suggestive and not suggestive of epileptogenic activity?

Participants will have a rs-fMRI and those with seizure networks will receive treatment with two antiseizure medications and a post-treatment rs-fMRI. Researchers will compare the pretreatment and post-treatment rs-fMRIs to see if there are changes in the participant's functional connectivity including seizure networks and typical resting state networks.

Enrollment: 5 patients

Sex: All

Ages: 18 months to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Currently ICU hospitalized.
• Suppression of consciousness related to a neurological injury by medical chart review.
• Glasgow Coma Scale of less than 13 at enrollment by medical chart review.
• Diagnosis of Acute brain injury by traumatic brain injury (TBI), hypoxic-ischemic insult, cardiac arrest, or stroke by medical chart review.
• 2 to 90 days from acute brain injury to enrollment time by medical chart review.
• Have a surface EEG performed after the current ICU admission
• Clinically stable to undergo MRI scan, This stability is defined by care team concept, which should be stated in the medical records.

Exclusion criteria

• Previous medical history of Epilepsy by medical chart review.
• Previous medical history of neurological sequels that lead to dependence on care for basic daily activities, by Barthel index score less than 80.
• Known allergy/Hypersensitivity or medical contraindications (like porphyria or cardiac arrhythmias) to the treatment protocol options, leaving no potential combination of drugs for the intervention without concerns for adverse events related to known preexistent conditions.
• Considered with Brain death by the care team in the medical record, at any time.
• Speaking fluently or at their prior reported baseline mental status by medical chart review before the intervention starts.
• Contraindications for MRI scan.
• Prisoner human subjects by medical chart review.
• Confirmed currently pregnant by medical history or by positive blood or urine pregnancy test done in the present hospital admission.
• Treating physician determines the patient is no candidate to receive 2 of the 5 protocol-specified ASM.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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5 participants in 2 patient groups

Seizure network Positive subjects

Experimental group

Description:

Participants in this group include all SzNET-Positive subjects, whether EEG-Positive or EEG-Negative. Within six days of their rs-fMRI #1 study, they will receive both loading and maintenance doses of two intervention drug regimens from the study list. For participants with a Glasgow Coma Scale (GCS) of 9 to 12, the research team will choose one of the two selected antiseizure medications (ASMs) and omit its loading dose. Maintenance doses should be administered every 12 hours, starting 12 hours after the loading dose, with a maximum of 19 doses allowed. A second rs-fMRI and EEG will occur after participants have received at least five maintenance doses. Following these assessments, the use of the intervention drugs as part of the research intervention will cease. However, if medically necessary, these drugs can continue as part of regular therapy. Note that repeat EEG and rs-fMRI assessments Must occur no longer than 72 hours after the last dose of the intervention drug regimen.

Treatment:

Drug: Levetiracetam

Drug: Fosphenytoin

Drug: Valproate Sodium

Drug: Phenobarbital Sodium Injection

Drug: Lacosamide Injectable Product

Seizure network Negative subjects

No Intervention group

Description:

Participants in this group encompass all SzNET-Negative subjects, including those who are EEG-Positive and EEG-Negative. These participants will not receive interventions after the initial study indicated rs-fMRI. They will neither receive repeat rs-fMRI or repeat EEG.