Antiseizure Medication in Seizure Networks at Early Acute Brain Injury

Stroke Clinical Trial

Official title:

Effect of Antiseizure Medication in Seizure Networks at Early Stages of Acute Brain Injury. The Rs-fMRI, Open-label Pilot Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06081283
• Other study ID #: 23-0157
• Status: Recruiting
• Phase: Phase 4
• Start date: November 20, 2023
• Est. completion date: February 2025

Study information

• Verified date: April 2024
• Source: University of North Carolina, Chapel Hill
• Contact: Emilio G. Cediel, MD
• Phone: 9847582948
• Email: egcediel[@]email.unc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 54
• Est. completion date: February 2025
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Brain Hypoxia
• Brain Injuries
• Brain Injuries, Acute
• Brain Injuries, Traumatic
• Brain Ischemia
• Coma
• Heart Arrest
• Hemorrhage
• Hypoxia
• Hypoxia, Brain
• Hypoxia-Ischemia, Brain
• Intracranial Hemorrhages
• Ischemia
• Persistent Vegetative State
• Seizures
• Stroke
• Wounds and Injuries

Intervention

Drug:
• Phenobarbital Sodium Injection
*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.
• Levetiracetam
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 Product
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 Sodium
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
• Phosphenytoin
Pediatric population Loading dose 20 mg 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.

Locations

Country	Name	City	State
United States	UNC Health	Chapel Hill	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pre and post-intervention seizure networks power spectrum medians	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	At the time of the second study rs-fMRI scan, which acquisition can be from 3 to 13 days after the intervention start date.
Primary	Pre and post-intervention seizure networks total volume medians	the medians from the normalized volume of the total seizure networks, of both pre and post-intervention rs-fMRI	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	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.	At the time of the first study rs-fMRI scan, which acquisition can be from 1 to 3 days after enrollment.
Secondary	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. Ictal-interictal continuum.	At the time of the follow-up study EEG, which acquisition can be from 3 to 13 days after the intervention start date.
Secondary	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	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	Enrollment rate	Number of participants enrolled divided by the amount of eligible patients screened.	The day of enrollment of each patient, and this will be collected through study completion, a duration of 1 year
Secondary	Dropout rate	Number of dropout participants divided by the amount of enrolled patients.	from enrollment to the second rs-fMRi acquisition time limit which means from 0 to 19 days from enrollment.