A Phase 4 interventional study of Phenobarbital Sodium Injection and Levetiracetam in Brain Injuries, Acute, Brain Injuries, Traumatic and Brain Ischemia, sponsored by University of North Carolina, Chapel Hill. Terminated at 1 site in United States. Open to participants aged 18 Months to 70 Years. Per ClinicalTrials.gov, last updated 2025-11-14.
Sponsored by University of North Carolina, Chapel Hill · Phase 4, Interventional, and Treatment
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:
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.
1,721 studies on the registry are indexed under Brain Injuries, Traumatic; 447 are open to participants now.
This study's enrollment of 5 is below the median of 52 across 1,088 interventional studies indexed under Brain Injuries, Traumatic.
Browse Brain Injuries, Traumatic studies →University of North Carolina, Chapel Hill is the lead sponsor of 1,372 studies on the registry; 133 are open to participants now.
Of its 161 completed or terminated interventional studies of FDA-regulated products, 139 (86%) have results posted.
Compared within Brain Injuries, Traumatic, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Brain Injuries. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Drug: Phenobarbital Sodium Injection · Drug: Levetiracetam · Drug: Lacosamide Injectable Product · Drug: Valproate Sodium · Drug: Fosphenytoin
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.
\*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.
Also known as: phenobarbital
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.
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.
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
Also known as: Valproate
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.
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.
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.
| Milestone | Seizure Network Positive Subjects | Seizure Network Negative Subjects |
|---|---|---|
| Started | 3 | 2 |
| Received initial phenobarbital sodium followed by lacosamide | 1 | 0 |
| Completed initial phenobarbital sodium followed by lacosamide | 1 | 0 |
| Received initial levetiracetam followed by lacosamide | 2 | 0 |
| Completed initial levetiracetam followed by lacosamide | 2 | 0 |
| Completed | 1 | 0 |
| Not completed | 2 | 2 |
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.
| Hz/10^2 | Seizure Network Positive Subjects | Seizure Network Negative Subjects |
|---|---|---|
| Pre-intervention rs-fMRI | 1.66 (-0.45 to 3.46) | — |
| Post-intervention rs-fMRI | 0.061 (0.049 to 3.43) | — |
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.
| voxels | Seizure Network Positive Subjects | Seizure Network Negative Subjects |
|---|---|---|
| Pre-intervention rs-fMRI | 3733.89 (3095.17 to 6378.14) | — |
| Post-intervention rs-fMRI | 3734.00 (3095.00 to 6378.00) | — |
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.
| Participants | Seizure Network Positive Subjects | Seizure Network Negative Subjects |
|---|---|---|
| Seizure networks present | 3 | 0 |
| Seizure networks absent | 0 | 2 |
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.
| Participants | Seizure Network Positive Subjects | Seizure Network Negative Subjects |
|---|---|---|
| With improvement | 0 | — |
| Without improvement | 3 | — |
Binary variable obtained by expert's opinion comparison between the typical resting state networks of the pre and post-intervention resting state functional MRIs
| Participants | Seizure Network Positive Subjects | Seizure Network Negative Subjects |
|---|---|---|
| Connectivity improvement | 2 | — |
| No connectivity improvement | 1 | — |
Number of participants enrolled divided by the amount of eligible participants screened.
| Participants | Seizure Network Positive Subjects |
|---|---|
| Enrollment Rate | 5 |
Number of dropout participants divided by the amount of enrolled participants.
| Participants | Seizure Network Positive Subjects | Seizure Network Negative Subjects |
|---|---|---|
| Dropout Rate | 2 | 2 |
Collected over Adverse events (AEs) temporally associated with the transport (varied up to 30 minutes round trip per scan) and scanning time for the rs-fMRI#1 or rs-fMRI #2 (25 minutes per scan), or during administration of the ASM intervention (up to 72 hours from initiation of ASM treatment prior to rs-fMRI #2). Thus, a total AE observation period of up to 74 hours.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Seizure Network Positive Subjects | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) |
| Seizure Network Negative Subjects | 2/2 (100%) | — | — |
| Age, Categorical(Participants) | Seizure Network Positive Subjects | Seizure Network Negative Subjects | Total |
|---|---|---|---|
| <=18 years | 1 | 0 | 1 |
| Between 18 and 65 years | 2 | 2 | 4 |
| >=65 years | 0 | 0 | 0 |
| Sex: Female, Male(Participants) | Seizure Network Positive Subjects | Seizure Network Negative Subjects | Total |
|---|---|---|---|
| Female | 1 | 1 | 2 |
| Male | 2 | 1 | 3 |
| Race and Ethnicity Not Collected(Participants) | Seizure Network Positive Subjects | Seizure Network Negative Subjects | Total |
|---|---|---|---|
| Count of participants | — | — | 0 |
| Region of Enrollment(Participants) | Seizure Network Positive Subjects | Seizure Network Negative Subjects | Total |
|---|---|---|---|
| United States | 3 | 2 | 5 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.
Time frame: beginning 9 and continuing for 36 months following publication
Access criteria: Investigator has approved IRB, IEC, or REB and an executed data use/sharing agreement with UNC.
Ran from Nov 2023 to primary completion in Dec 2024, 13 months.
Results were first posted in Nov 2025, 10 months after primary completion.
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This study is terminated, as verified in Jul 2025. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Phenobarbital · Levetiracetam · Lacosamide · Valproic Acid · Fosphenytoin
University of North Carolina, Chapel Hill →