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Antiseizure Medication in Seizure Networks at Early Acute Brain Injury

Primary Purpose

Brain Injuries, Acute, Brain Injuries, Traumatic, Brain Ischemia

Status

Not yet recruiting

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Phenobarbital Sodium Injection

Levetiracetam

Lacosamide Injectable Product

Valproate Sodium

Phosphenytoin

About this trial

This is an interventional treatment trial for Brain Injuries, Acute focused on measuring Coma, Vegetative state, Suppression of consciousness, antiseizure medication, Brain networks, Functional connectivity, Unresponsive wakefulness, Functional MRI, Resting state, Brain Injuries, Acute

Eligibility Criteria

6 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Currently ICU hospitalized. Glasgow Coma Scale of less than 9 at ICU admission by medical chart review. Diagnosis of Acute brain injury by TBI, hypoxic-ischemic insult, cardiac arrest, or stroke by medical chart review. 3 to 45 days from acute brain injury to enrollment time by medical chart review. 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.

Sites / Locations

UNC Health

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Seizure network Positive subjects

Seizure network Negative subjects

Arm Description

Participants in this group encompass all SzNET-Positive subjects, including those who are EEG-Positive and EEG-Negative. Within six days of their initial rs-fMRI study, they will receive both loading and maintenance doses of two of the intervention drug regimens from the study's list. Maintenance doses should be administered every 12 hours, commencing 12 hours after the loading dose, with a maximum of 19 maintenance doses allowed. A second rs-fMRI and EEG will be conducted after participants have received at least five maintenance doses. Following these follow-up rs-fMRI and EEG assessments, the use of the intervention drugs as part of the research intervention will be discontinued. However, if medically necessary, these drugs can continue as part of regular therapy. It's important to note that repeat EEG and rs-fMRI assessments cannot be conducted if more than 72 hours have passed since the last dose of the intervention drug regimen.

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.

Outcomes

Primary Outcome Measures

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

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

Secondary Outcome Measures

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.

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.

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

Enrollment rate

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

Dropout rate

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

Full Information

NCT ID

NCT06081283

First Posted

September 28, 2023

Last Updated

October 6, 2023

Sponsor

University of North Carolina, Chapel Hill

1. Study Identification

Unique Protocol Identification Number

NCT06081283

Brief Title

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

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

October 2023 (Anticipated)

Primary Completion Date

November 2024 (Anticipated)

Study Completion Date

February 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of North Carolina, Chapel Hill

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Sequential Assignment

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

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

54 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Seizure network Positive subjects

Arm Type

Experimental

Arm Description

Arm Title

Seizure network Negative subjects

Arm Type

No Intervention

Arm Description

Intervention Type

Drug

Intervention Name(s)

Phenobarbital Sodium Injection

Other Intervention Name(s)

phenobarbital

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Levetiracetam

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Lacosamide Injectable Product

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Valproate Sodium

Other Intervention Name(s)

Valproate

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Phosphenytoin

Intervention Description

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.

Primary Outcome Measure Information:

Title

Pre and post-intervention seizure networks power spectrum medians

Description

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

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.

Title

Pre and post-intervention seizure networks total volume medians

Description

the medians from the normalized volume of the total seizure networks, of both pre and post-intervention rs-fMRI

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 Outcome Measure Information:

Title

Presence of seizure networks in the first resting state functional MRI

Description

Binary Variable. The total amount of participants for this outcome measure will include only the subjects enrolled until the first sampling quota is completed.

Time Frame

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

Title

Follow-up electroencephalogram improvement

Description

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.

Title

Connectivity improvement of typical resting state networks after intervention

Description

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.

Title

Enrollment rate

Description

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

Time Frame

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

Title

Dropout rate

Description

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

Time Frame

from enrollment to the second rs-fMRi acquisition time limit which means from 0 to 19 days from enrollment.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Emilio G. Cediel, MD

Phone

9847582948

egcediel@email.unc.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Varina L Boerwinkle, MD

Phone

9199669343

Varina_Boerwinkle@med.unc.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Emilio G. Cediel, MD

Organizational Affiliation

UNC-Chapel Hill

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Varina L Boerwinkle, MD

Organizational Affiliation

UNC-Chapel Hill

Official's Role

Study Chair

Facility Information:

Facility Name

UNC Health

City

Chapel Hill

State/Province

North Carolina

ZIP/Postal Code

27599

Country

United States

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Emilio G Cediel, MD

Phone

984-758-2948

egcediel@email.unc.edu

First Name & Middle Initial & Last Name & Degree

Varina L Boerwinkle, MD

Phone

9199669343

Varina_Boerwinkle@med.unc.edu

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

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.

IPD Sharing Time Frame

beginning 9 and continuing for 36 months following publication

IPD Sharing Access Criteria

Investigator has approved IRB, IEC, or REB and an executed data use/sharing agreement with UNC.

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Antiseizure Medication in Seizure Networks at Early Acute Brain Injury

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