Vigabatrin for Post-anoxic Seizures

(VIGAB-STAT Trial)

Overseen By Ralisa Pop, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Florida

Disqualifiers: Generalized epilepsy, Recent GI surgery, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 48 hours

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a single dose of the drug vigabatrin can help individuals experiencing seizures after a non-traumatic cardiac arrest. Participants must have been diagnosed with these seizures through brain monitoring and require ongoing anesthetic treatment. The trial may suit those who can reliably take medications and undergo frequent blood tests. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that vigabatrin is likely to be safe for humans?

Research has shown that many patients have safely used vigabatrin to treat seizures. Common side effects include drowsiness and insomnia, but these are usually mild. In rare cases, more serious side effects may occur.

Vigabatrin is already approved for treating other types of seizures, indicating prior safety studies. However, this trial is in an early stage, so there is less information about its safety specifically for treating seizures after a lack of oxygen to the brain. More research is needed to fully understand how well vigabatrin works in this new context. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Vigabatrin is unique because it works by increasing levels of gamma-aminobutyric acid (GABA) in the brain, which helps to calm overactive neural activity. Unlike traditional treatments for post-anoxic seizures, such as benzodiazepines or barbiturates, which primarily target GABA receptors, vigabatrin inhibits the enzyme responsible for breaking down GABA, leading to a sustained increase in its levels. Researchers are excited about this approach because it offers a novel mechanism that could provide more effective seizure control, especially in cases where other medications have failed. Additionally, its enteral administration allows for direct delivery to the digestive system, potentially improving absorption and effectiveness.

What evidence suggests that vigabatrin might be an effective treatment for post-anoxic seizures?

Research has shown that vigabatrin might help reduce seizures following oxygen deprivation in the brain, such as after a heart attack. In animal studies, vigabatrin not only reduced seizure severity but also lowered mortality rates. Vigabatrin increases GABA, a brain chemical that calms nerve activity, which may be crucial for controlling seizures. Although research in humans continues, these early results are promising for using vigabatrin to manage seizures after oxygen loss. ^{1 2 3 6 7}

Who Is on the Research Team?

Carolina B Maciel, MD, MSCR

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

This trial is for adults over 18 who've had a non-traumatic cardiac arrest and are in a coma with continuous epileptic seizures, requiring anesthesia. They must have reliable arterial access for blood tests and a way to receive medication through the digestive system within 48 hours of seizure onset.

Inclusion Criteria

You had a sudden stop in your heart that wasn't caused by an injury, and your doctor has decided that you need treatment for continuous abnormal brain activity.

You need anesthesia for any reason.

You need to have a good artery that can be used to take blood samples often.

Exclusion Criteria

History of gastrointestinal surgery within the last 21 days

Pregnancy

You have had seizures all over your body before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

48 hours

Treatment

A single loading dose of vigabatrin is administered within 48 hours of post-anoxic status epilepticus onset

48 hours

In-hospital administration

Monitoring

Serial blood tests are obtained to monitor vigabatrin levels, taurine levels, and other biomarkers

7 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including visual field perimetry at 6 months

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Vigabatrin

Trial Overview The study is testing the effects of a single dose of vigabatrin, which is given to patients experiencing persistent epileptic seizures after cardiac arrest. The goal is to see how well it works when standard treatments aren't enough.

How Is the Trial Designed?

Group I: Open label Experimental Treatment 1 Intervention

4500 mg of vigabatrin administered enterally

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

Thomas Jefferson University

Collaborator

Trials

475

Recruited

189,000+

Yale University

Collaborator

Trials

1,963

Recruited

3,046,000+

American Heart Association

Collaborator

Trials

352

Recruited

6,196,000+

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1525505024004645

Early vigabatrin to augment GABAergic pathways in post- ... Outcomes in post-anoxic status epilepticus are dismal despite advances in resuscitation. · Effective therapies targeting hyperexcitability from cardiac arrest ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35067230/

Early vigabatrin augmenting GABA-ergic pathways in post ... This is a phase IIa, single-center, open-label, pilot clinical trial with blinded outcome assessment, of a single dose of vigabatrin in 12 consecutive PASE ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04772547

VIGABatrin in Post-anoxic STATus Epilepticus - Phase IIa This pilot trial aims to demonstrate the feasibility of enteral administration of a single load of vigabatrin within targeted 48 hours of post-anoxic status ...

4. withpower.com withpower.com/trial/phase-3-status-epilepticus-6-2021-2b883

Vigabatrin for Post-anoxic Seizures (VIGAB-STAT Trial) In animal studies, Vigabatrin reduced seizure severity and mortality when administered after hypoxia (low oxygen levels), suggesting it may help in similar ...

5. neurology.ufl.edu neurology.ufl.edu/2024/10/22/early-vigabatrin-to-augment-gaba-ergic-pathways-in-post-anoxic-status-epilepticus/

Early vigabatrin to augment GABA-ergic pathways in post ... The outcomes of patients who experience status epilepticus during the post-cardiac arrest period, or post-anoxic status epilepticus (PASE), ...

6. mdpi.com mdpi.com/1422-0067/22/13/7121

Treating Seizures after Hypoxic-Ischemic Encephalopathy ... These data strongly suggest that seizures were largely bystanders to the overall evolving injury rather than a major contributing factor.

7. mayoclinic.elsevierpure.com mayoclinic.elsevierpure.com/en/publications/early-vigabatrin-augmenting-gaba-ergic-pathways-in-post-anoxic-st

Early vigabatrin augmenting GABA-ergic pathways in post ... Vigabatrin—an approved therapy for refractory focal-onset seizures in adults—inhibits the enzyme responsible for GABA catabolism, increases brain GABA levels ...