Clinical trial NCT06081283: Antiseizure Medication in Seizure Networks at Early Acute Brain Injury
Official title: Effect of Antiseizure Medication in Seizure Networks at Early Stages of Acute Brain Injury. The Rs-fMRI, Open-label Pilot Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Brain Injuries, Acute
Brain Injuries, Traumatic
Brain Ischemia
Brain Hypoxia
Hypoxia-Ischemia, Brain
Heart Arrest
Stroke
Intracranial Hemorrhages
Coma
Persistent Vegetative State
Keywords: Coma
Vegetative state
Suppression of consciousness
antiseizure medication
Brain networks
Functional connectivity
Unresponsive wakefulness
Functional MRI
Resting state
Brain Injuries, Acute
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
First posted: 2023-10-13
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Subjects will be enrolled irrespective of their electroencephalogram (EEG) results, whether positive(+) or negative(-) for epileptogenic activity. All enrolled subjects will undergo an initial resting-state functional MRI (rsfMRI). The results will categorize the patients based on the presence or absence of seizure networks (SzNET), resulting in 2 groups: SzNET+ and SzNET-. SzNET- participants will not undergo further interventions or tests, while SzNET+ subjects will be assigned to the intervention arm and will receive follow-up rsfMRI and EEG.

The study aims to fill 2 quotas in its intervention arm: Participants who are both SzNET+ and EEG+, and another for those SzNET+ but EEG-. Once either of these quotas is complete, the study will cease screening subjects with EEG results falling into that quota. The subjects discharged from hospital on antiseizure medications for medical reasons will be followed up at 3 months post-discharge to collect exploratory data
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Pre and post-intervention seizure networks power spectrum medians
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.
measure: Pre and post-intervention seizure networks total volume medians
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.
Secondary outcomes:
measure: Presence of seizure networks in the first resting state functional MRI
timeFrame: At the time of the first study rs-fMRI scan, which acquisition can be from 1 to 3 days after enrollment.
measure: Follow-up electroencephalogram improvement
timeFrame: At the time of the follow-up study EEG, which acquisition can be from 3 to 13 days after the intervention start date.
measure: Connectivity improvement of typical resting state networks after intervention
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.
measure: Enrollment rate
timeFrame: The day of enrollment of each patient, and this will be collected through study completion, a duration of 1 year
measure: Dropout rate
timeFrame: from enrollment to the second rs-fMRi acquisition time limit which means from 0 to 19 days from enrollment.
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: UNC Health
state: North Carolina
Study officials:
affiliation: UNC-Chapel Hill
name: Emilio G. Cediel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: UNC-Chapel Hill
name: Varina L Boerwinkle, MD
role: STUDY_CHAIR
References: