Trial Outcomes & Findings for Antiseizure Medication in Seizure Networks at Early Acute Brain Injury (NCT NCT06081283)
NCT ID: NCT06081283
Last Updated: 2025-11-14
Results Overview
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.
TERMINATED
PHASE4
5 participants
At the time of the second study rs-fMRI scan, which acquisition can be from 3 to 13 days after the intervention start date.
2025-11-14
Participant Flow
No participants were enrolled with a Glasgow Coma Scale (GCS) score of 9 to 12. The intervention phase occurs between resting state functional magnetic resonance imaging (rs-fMRI#1) and the day of follow-up rs-fMRI#2 and repeated EEG. The intervention is considered complete and the follow-up tests can be done if the patient received the study antiseizure medication (ASM) for at least 72 hours after the loading dose, and the second scan was done within 72 hours of the last intervention ASM dose.
Participant milestones
| Measure |
Seizure Network Positive Subjects
All seizure network positive (SzNET-Positive) participants, 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 Glasgow Coma Scale (GCS) score 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.
The possible intervention drug regimens used were: Phenobarbital Sodium Injection, Levetiracetam, Lacosamide Injectable Product, Valproate Sodium, and fosphenytoin. The key intervention and first option to be considered will be phenobarbital + levetiracetam. For clinical reasons the care team may select any combination of two or more study listed ASM regimens. For further specifics on loading and maintenance dosages please refer to the Arms and Interventions section of the Protocol Record.
|
Seizure Network Negative Subjects
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.
|
|---|---|---|
|
Overall Study
STARTED
|
3
|
2
|
|
Overall Study
Received Initial Phenobarbital Sodium Followed by Lacosamide
|
1
|
0
|
|
Overall Study
Completed Initial Phenobarbital Sodium Followed by Lacosamide
|
1
|
0
|
|
Overall Study
Received Initial Levetiracetam Followed by Lacosamide
|
2
|
0
|
|
Overall Study
Completed Initial Levetiracetam Followed by Lacosamide
|
2
|
0
|
|
Overall Study
COMPLETED
|
1
|
0
|
|
Overall Study
NOT COMPLETED
|
2
|
2
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Seizure Network Positive Subjects
n=3 Participants
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.
The possible intervention drug regimens used were: Phenobarbital Sodium Injection, Levetiracetam, Lacosamide Injectable Product, Valproate Sodium, and fosphenytoin. For further specifics on loading and maintenance dosages please refer to the Arms and Interventions section of the Protocol Record.
|
Seizure Network Negative Subjects
n=2 Participants
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.
|
Total
n=5 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Region of Enrollment
United States
|
3 Participants
n=3 Participants
|
2 Participants
n=2 Participants
|
5 Participants
n=5 Participants
|
|
Age, Categorical
<=18 years
|
1 Participants
n=3 Participants
|
0 Participants
n=2 Participants
|
1 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
2 Participants
n=3 Participants
|
2 Participants
n=2 Participants
|
4 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=3 Participants
|
0 Participants
n=2 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=3 Participants
|
1 Participants
n=2 Participants
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=3 Participants
|
1 Participants
n=2 Participants
|
3 Participants
n=5 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
PRIMARY outcome
Timeframe: At the time of the second study rs-fMRI scan, which acquisition can be from 3 to 13 days after the intervention start date.Population: This outcome does not apply to the Seizure Network Negative Subjects; therefore, no data were collected for this group.
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.
Outcome measures
| Measure |
Seizure Network Positive Subjects
n=3 Participants
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 Glasgow Coma Scale (GCS) score 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.
The possible intervention drug regimens used were: Phenobarbital Sodium Injection, Levetiracetam, Lacosamide Injectable Product, Valproate Sodium, and fosphenytoin. The key intervention and first option to be considered will be phenobarbital + levetiracetam. For clinical reasons the care team may select any combination of two or more study listed ASM regimens. For further specifics on loading and maintenance dosages please refer to the Arms and Interventions section of the Protocol Record.
|
Seizure Network Negative Subjects
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.
|
|---|---|---|
|
Pre and Post-intervention Seizure Networks Power Spectrum Medians
Pre-intervention rs-fMRI
|
1.66 Hz/10^2
Interval -0.45 to 3.46
|
—
|
|
Pre and Post-intervention Seizure Networks Power Spectrum Medians
Post-intervention rs-fMRI
|
0.061 Hz/10^2
Interval 0.049 to 3.43
|
—
|
PRIMARY outcome
Timeframe: At the time of the second study rs-fMRI scan, which acquisition can be from 3 to 13 days after the intervention start date.Population: This outcome does not apply to the Seizure Network Negative Subjects; therefore, no data were collected for this group.
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.
Outcome measures
| Measure |
Seizure Network Positive Subjects
n=3 Participants
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 Glasgow Coma Scale (GCS) score 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.
The possible intervention drug regimens used were: Phenobarbital Sodium Injection, Levetiracetam, Lacosamide Injectable Product, Valproate Sodium, and fosphenytoin. The key intervention and first option to be considered will be phenobarbital + levetiracetam. For clinical reasons the care team may select any combination of two or more study listed ASM regimens. For further specifics on loading and maintenance dosages please refer to the Arms and Interventions section of the Protocol Record.
|
Seizure Network Negative Subjects
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.
|
|---|---|---|
|
Pre and Post-intervention Seizure Networks Total Volume Medians
Pre-intervention rs-fMRI
|
3733.89 voxels
Interval 3095.17 to 6378.14
|
—
|
|
Pre and Post-intervention Seizure Networks Total Volume Medians
Post-intervention rs-fMRI
|
3734.00 voxels
Interval 3095.0 to 6378.0
|
—
|
SECONDARY outcome
Timeframe: 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. Only the two SzNET+ groups have a minimum enrollment goal. Thus, enrollment will stop once each of the two SzNET+ groups enroll ten patients.
Outcome measures
| Measure |
Seizure Network Positive Subjects
n=3 Participants
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 Glasgow Coma Scale (GCS) score 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.
The possible intervention drug regimens used were: Phenobarbital Sodium Injection, Levetiracetam, Lacosamide Injectable Product, Valproate Sodium, and fosphenytoin. The key intervention and first option to be considered will be phenobarbital + levetiracetam. For clinical reasons the care team may select any combination of two or more study listed ASM regimens. For further specifics on loading and maintenance dosages please refer to the Arms and Interventions section of the Protocol Record.
|
Seizure Network Negative Subjects
n=2 Participants
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.
|
|---|---|---|
|
Presence of Seizure Networks in the First Resting State Functional MRI
Seizure networks present
|
3 Participants
|
0 Participants
|
|
Presence of Seizure Networks in the First Resting State Functional MRI
Seizure networks absent
|
0 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: At the time of the follow-up study EEG, which acquisition can be from 3 to 13 days after the intervention start date.Population: Follow-up EEG activity only includes Seizure Network Positive Subjects; therefore, no data were collected for the Seizure Network Negative Subjects arm.
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.
Outcome measures
| Measure |
Seizure Network Positive Subjects
n=3 Participants
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 Glasgow Coma Scale (GCS) score 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.
The possible intervention drug regimens used were: Phenobarbital Sodium Injection, Levetiracetam, Lacosamide Injectable Product, Valproate Sodium, and fosphenytoin. The key intervention and first option to be considered will be phenobarbital + levetiracetam. For clinical reasons the care team may select any combination of two or more study listed ASM regimens. For further specifics on loading and maintenance dosages please refer to the Arms and Interventions section of the Protocol Record.
|
Seizure Network Negative Subjects
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.
|
|---|---|---|
|
Follow-up Electroencephalogram Improvement
With improvement
|
0 Participants
|
—
|
|
Follow-up Electroencephalogram Improvement
Without improvement
|
3 Participants
|
—
|
SECONDARY outcome
Timeframe: At the time of the second study rs-fMRI scan, which acquisition can be from 3 to 13 days after the intervention start date.Population: Connectivity of typical resting state networks only includes Seizure Network Positive Subjects; therefore, no data were collected for the Seizure Network Negative Subjects arm.
Binary variable obtained by expert's opinion comparison between the typical resting state networks of the pre and post-intervention resting state functional MRIs
Outcome measures
| Measure |
Seizure Network Positive Subjects
n=3 Participants
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 Glasgow Coma Scale (GCS) score 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.
The possible intervention drug regimens used were: Phenobarbital Sodium Injection, Levetiracetam, Lacosamide Injectable Product, Valproate Sodium, and fosphenytoin. The key intervention and first option to be considered will be phenobarbital + levetiracetam. For clinical reasons the care team may select any combination of two or more study listed ASM regimens. For further specifics on loading and maintenance dosages please refer to the Arms and Interventions section of the Protocol Record.
|
Seizure Network Negative Subjects
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.
|
|---|---|---|
|
Connectivity Improvement of Typical Resting State Networks After Intervention
No connectivity improvement
|
1 Participants
|
—
|
|
Connectivity Improvement of Typical Resting State Networks After Intervention
Connectivity improvement
|
2 Participants
|
—
|
SECONDARY outcome
Timeframe: The day of enrollment of each patient, and this will be collected through study completion, a duration of 1 yearNumber of participants enrolled divided by the amount of eligible participants screened.
Outcome measures
| Measure |
Seizure Network Positive Subjects
n=74 Participants
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 Glasgow Coma Scale (GCS) score 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.
The possible intervention drug regimens used were: Phenobarbital Sodium Injection, Levetiracetam, Lacosamide Injectable Product, Valproate Sodium, and fosphenytoin. The key intervention and first option to be considered will be phenobarbital + levetiracetam. For clinical reasons the care team may select any combination of two or more study listed ASM regimens. For further specifics on loading and maintenance dosages please refer to the Arms and Interventions section of the Protocol Record.
|
Seizure Network Negative Subjects
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.
|
|---|---|---|
|
Enrollment Rate
|
5 Participants
|
—
|
SECONDARY outcome
Timeframe: 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 participants.
Outcome measures
| Measure |
Seizure Network Positive Subjects
n=3 Participants
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 Glasgow Coma Scale (GCS) score 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.
The possible intervention drug regimens used were: Phenobarbital Sodium Injection, Levetiracetam, Lacosamide Injectable Product, Valproate Sodium, and fosphenytoin. The key intervention and first option to be considered will be phenobarbital + levetiracetam. For clinical reasons the care team may select any combination of two or more study listed ASM regimens. For further specifics on loading and maintenance dosages please refer to the Arms and Interventions section of the Protocol Record.
|
Seizure Network Negative Subjects
n=2 Participants
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.
|
|---|---|---|
|
Dropout Rate
|
2 Participants
|
2 Participants
|
Adverse Events
Seizure Network Positive Subjects
Seizure Network Negative Subjects
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Meitra Kazemi
University of North Carollina at Chapel Hill
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place