Antiseizure Medication in Seizure Networks at Early Acute Brain Injury

Phase 4

Active, not recruiting

• Conditions: Hypoxia-Ischemia, Brain; Brain Ischemia; Persistent Vegetative State; Brain Hypoxia; Heart Arrest; Stroke; Brain Injuries, Acute; Brain Injuries, Traumatic; Intracranial Hemorrhages; Coma
• Interventions: Drug: Phenobarbital Sodium Injection; Drug: Levetiracetam; Drug: Lacosamide Injectable Product; Drug: Valproate Sodium; Drug: Phosphenytoin

• Registration Number: NCT06081283
• Lead Sponsor: University of North Carolina, Chapel Hill

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-09-28
• Study First Submitted QC: 2023-10-06
• Study First Posted: 2023-10-13
• Study Start: 2023-11-20
• Primary Completion: 2025-01-26
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-11
• Last Update Posted: 2025-02-12
• Study Completion: 2025-04

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 54

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 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Seizure network Positive subjects	Lacosamide Injectable Product	Participants in this group include all SzNET-Positive subjects, whether EEG-Positive or EEG-Negative. Within six days of their initial rs-fMRI study, they will receive both loading and maintenance doses of two intervention drug regimens from the study's list. For participants with a GCS of 9 to 12, the research team will choose one of the two selected ASMs, and will 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.
Seizure network Positive subjects	Phenobarbital Sodium Injection	Participants in this group include all SzNET-Positive subjects, whether EEG-Positive or EEG-Negative. Within six days of their initial rs-fMRI study, they will receive both loading and maintenance doses of two intervention drug regimens from the study's list. For participants with a GCS of 9 to 12, the research team will choose one of the two selected ASMs, and will 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.
Seizure network Positive subjects	Valproate Sodium	Participants in this group include all SzNET-Positive subjects, whether EEG-Positive or EEG-Negative. Within six days of their initial rs-fMRI study, they will receive both loading and maintenance doses of two intervention drug regimens from the study's list. For participants with a GCS of 9 to 12, the research team will choose one of the two selected ASMs, and will 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.
Seizure network Positive subjects	Phosphenytoin	Participants in this group include all SzNET-Positive subjects, whether EEG-Positive or EEG-Negative. Within six days of their initial rs-fMRI study, they will receive both loading and maintenance doses of two intervention drug regimens from the study's list. For participants with a GCS of 9 to 12, the research team will choose one of the two selected ASMs, and will 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.
Seizure network Positive subjects	Levetiracetam	Participants in this group include all SzNET-Positive subjects, whether EEG-Positive or EEG-Negative. Within six days of their initial rs-fMRI study, they will receive both loading and maintenance doses of two intervention drug regimens from the study's list. For participants with a GCS of 9 to 12, the research team will choose one of the two selected ASMs, and will 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.

Primary Outcome Measures

Name	Time	Method
Pre and post-intervention seizure networks power spectrum medians	At the time of the second study rs-fMRI scan, which acquisition can be from 3 to 13 days after the intervention start date.	the medians from the normalized and volume-adjusted, area under the curve of the seizure networks power spectrum curve above 6.78 Hz/100, of both pre and post-intervention rs-fMRI
Pre and post-intervention seizure networks total volume medians	At the time of the second study rs-fMRI scan, which acquisition can be from 3 to 13 days after the intervention start date.	the medians from the normalized volume of the total seizure networks, of both pre and post-intervention rs-fMRI

Secondary Outcome Measures

Name	Time	Method
Presence of seizure networks in the first resting state functional MRI	At the time of the first study rs-fMRI scan, which acquisition can be from 1 to 3 days after enrollment.	Binary Variable. The total amount of participants for this outcome measure will include only the subjects enrolled until the first sampling quota is completed.
Dropout rate	from enrollment to the second rs-fMRi acquisition time limit which means from 0 to 19 days from enrollment.	Number of dropout participants divided by the amount of enrolled patients.
Follow-up electroencephalogram improvement	At the time of the follow-up study EEG, which acquisition can be from 3 to 13 days after the intervention start date.	Binary variable categorized as "with improvement" or "without improvement", obtained by expert's overall qualitative assessment comparing the follow-up study EEG and the clinically indicated EEG considered at the enrollment time. The qualitative assessment will be based on the EEG's background and the presence of electrophysiological signs of ictal or interictal activity.; These signs are described by the American Clinical Neurophysiology Society as: Epileptiform Discharges Rhythmic and periodic patterns Electrographic and electroclinical seizures. Ictal-interictal continuum.
Connectivity improvement of typical resting state networks after intervention	At the time of the second study rs-fMRI scan, which acquisition can be from 3 to 13 days after the intervention start date.	Binary variable obtained by expert's opinion comparison between the typical resting state networks of the pre and post-intervention resting state functional MRIs
Enrollment rate	The day of enrollment of each patient, and this will be collected through study completion, a duration of 1 year	Number of participants enrolled divided by the amount of eligible patients screened.

Trial Locations

Locations (1)

UNC Health; 🇺🇸 Chapel Hill, North Carolina, United States