Antiseizure Medication in Seizure Networks at Early Acute Brain Injury

Phase 4TerminatedNCT06081283

University of North Carolina, Chapel Hill5 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Brain Injuries, Acute Brain Injuries, Traumatic Brain Ischemia

Interventions

Phenobarbital Sodium InjectionDRUG

\*This drug can only be selected as part of the intervention for the subgroup of patients with a Glasgow Coma Score of 8 or less. Loading dose 20 mg/kg intravenous. Max dose 1000mg Maintenance dose 4mg/kg/day. Max dose 300mg/day. Adult population Loading dose 20 mg/kg intravenous. Maintenance dose 4mg/kg/day.

LevetiracetamDRUG

Pediatric population Loading dose 60 mg/kg intravenous. Max dose 4000mg. Maintenance dose 40mg/Kg/day, Max dose 3000mg/day. Adult population Loading dose 2000mg-4000mg intravenous. Maintenance dose 1500mg to 3000mg/day.

Lacosamide Injectable ProductDRUG

Pediatric population Loading dose 10 mg/kg intravenous, Max dose 400mg. Maintenance dose 4mg to 8mg/Kg/day. Max dose 300mg. Adult population Loading dose 200mg to 400mg intravenous. Maintenance dose 200mg to 400mg/day.

Valproate SodiumDRUG

Pediatric population Loading dose 30mg/kg intravenous. Max dose 3000mg Maintenance dose 20mg to 30mg/Kg/day, Max dose 3000mg/day. Adult population Loading dose 30 mg/kg intravenous. Maintenance dose 20mg to 30mg/Kg/day

FosphenytoinDRUG

Pediatric population Loading dose 20 mg phenytoin equivalents (PE)/kg intravenous. Max dose 1500mg PE Maintenance dose 4mg PE/Kg/day. Max dose 300mg PE/day. Adult population Loading dose 20 mg/kg intravenous. Max dose 1500mg PE Maintenance dose 4mg PE/Kg/day.

Eligibility

Sex: ALLMin age: 18 MonthsMax age: 70 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Pre and Post-intervention Seizure Networks Power Spectrum Medians

Power spectral analysis identifies differences in Blood Oxygen Level Dependent (BOLD) changes between different cortical areas, cognitive states, or frequency bands that may reflect a pattern of component frequencies. The power spectrum graph shows the BOLD signal's power density over multiple frequencies, measured in Hz/100. Power Spectrum (PS) is the sum of the PS of the SzNET independent components normalized by their spatial volumes. Functional scans were co-registered to the anatomical T1 image, visually inspected, and subjected to independent component analysis (ICA) using the FMRIB Software Library (FSL) tool MELODIC. ICA was applied to separate the BOLD signal into independent components generated by brain networks, which were evaluated for suspected seizure onset zones (SOZs) based on spatial and temporal features. Pre- and post-intervention Rs-fMRI medians were found from the normalized and volume-adjusted area under the curve of the SzNET PS curve above 6.78 Hz/100.

Time frame: At the time of the second study rs-fMRI scan, which acquisition can be from 3 to 13 days after the intervention start date.

Pre and Post-intervention Seizure Networks Total Volume Medians

Rs-fMRI data is collected as 2 runs of 10-minute data collection on a 3T MRI scanner. One volume from the fMRI is a complete slice of the brain's activity at a specific point of time. Over the 20-minute period that the rs-fMRI is performed, many volumes are collected at different time points continuously throughout the scan. These volume elements are measured in units of voxels which are a 3D unit of the MRI image. SzNET total volume (TV) is the sum of the volumes of the SzNET independent components, collected through ICA where independent components generated by brain networks were evaluated for suspected seizure onset zones. The medians from the normalized volume of the total seizure networks, of both pre and post-intervention rs-fMRI, were collected from this data.

Time frame: At the time of the second study rs-fMRI scan, which acquisition can be from 3 to 13 days after the intervention start date.

Secondary Outcomes

Presence of Seizure Networks in the First Resting State Functional MRI

Binary Variable. The total amount of participants for this outcome measure will include only the subjects enrolled until the first sampling quota is completed. Only the two SzNET+ groups have a minimum enrollment goal. Thus, enrollment will stop once each of the two SzNET+ groups enroll ten patients.

Time frame: At the time of the first study rs-fMRI scan, which acquisition can be from 1 to 3 days after enrollment.

Follow-up Electroencephalogram Improvement

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; and Ictal-interictal continuum.

Time frame: At the time of the follow-up study EEG, which acquisition can be from 3 to 13 days after the intervention start date.

Connectivity Improvement of Typical Resting State Networks After Intervention

Binary variable obtained by expert's opinion comparison between the typical resting state networks of the pre and post-intervention resting state functional MRIs

Time frame: At the time of the second study rs-fMRI scan, which acquisition can be from 3 to 13 days after the intervention start date.

Enrollment Rate

Number of participants enrolled divided by the amount of eligible participants screened.

Time frame: The day of enrollment of each patient, and this will be collected through study completion, a duration of 1 year

Dropout Rate

Number of dropout participants divided by the amount of enrolled participants.

Time frame: from enrollment to the second rs-fMRI acquisition time limit which means from 0 to 19 days from enrollment.

Antiseizure Medication in Seizure Networks at Early Acute Brain Injury

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes