Epilepsy trial studies new drug to treat severe seizures
UC Department of Neurology one of 50 trial sites nationwide
A new clinical trial at the University of Cincinnati will study a new treatment for the most severe and deadly form of epilepsy.
Brandon Foreman, MD, is the site principal investigator at UC for the Researching Established Status Epilepticus Treatment (RESET) study, a trial being conducted across approximately 50 hospital emergency departments across the country.
The trial focuses on a condition known as status epilepticus (SE), a disorder Foreman described as “seizures that don’t stop.” SE is the second most common neurologic emergency in the United States, and more than 150,000 Americans experience SE each year. Based on factors including age and the cause and duration of the seizures, between 20% to 30% of patients with SE do not survive.
About half of patients who have SE have a previous history of epilepsy and seizures, but the other half have no history of seizures. When a seizure goes on for more than five minutes, Foreman said it enters a “dangerous territory” where the seizure may not stop on its own without medication.
The current standard treatments for SE include paramedics administering drugs on the way to the hospital that activate specific GABA receptors in the brain that sit on the ends of neurons. These receptors communicate to slow down other neurons, so strengthening that connection helps suppress seizures.
A large dose of anti-seizure medication is then given once a patient reaches the hospital. But about a quarter of patients’ seizures still do not stop after receiving these initial medications.
“Right now the only way to manage them is to put them on anesthetic medications, so it’s a continuous drip medication to induce coma,” said Foreman, associate professor and associate director of neurocritical care research in the Department of Neurology and Rehabilitation Medicine in UC’s College of Medicine and a UC Health physician. “And that’s been associated with some bad outcomes. It’s not a good thing to come into the ICU and then be put into a coma, and there’s nothing to fill the gap.”
If we can avoid patients not progressing to the need for IV anesthesia, intubation and an ICU stay that can sometimes be prolonged, that’s going to be lifesaving.
Brandon Foreman, MD
Foreman said the RESET study will test a new medication that will be administered after the first anti-seizure medication in emergency departments for those patients whose seizures persist.
“We’re pushing this medication forward in care so it’s actually hopefully fitting in that gap where they’re getting the second anti-seizure medication and we can stave off the progression to needing anesthesia to really get these under control,” he said.
The GABA receptors targeted by the first line of drugs administered in ambulances can melt away during a seizure, Foreman noted, making the drugs less effective at stopping the seizure. The drug being studied in the trial, ganaxolone, works differently.
“It’s a neurosteroid, so it’s a derivative of something your brain already makes,” Foreman said. “It’s hitting a very similar inhibitory transmitter or channel, but it’s doing so using those receptors that haven’t melted away as a result of the seizures.”
Patients who come into the emergency department with SE that doesn’t stop after the initial round of medications will be enrolled into the RESET study, with the trial drug added to the current standard of care.
“It’s not a medicine that [is administered] for weeks or that they can take as an outpatient; it’s a study that’s pretty short in general,” Foreman said. “It’s just while you’re there in the [emergency department], and our endpoint is just looking if the seizures stop.”
Foreman said if the drug stops seizures before the need for a medically induced coma, it will fill a significant gap in care for SE.
“If we can avoid patients not progressing to the need for IV anesthesia, intubation and an ICU stay that can sometimes be prolonged, that’s going to be lifesaving,” he said. “It’s probably going to improve outcomes dramatically for people that are responsive to this kind of treatment.”
Exception from informed consent
Because of the short time frame where drugs can be given to stop SE, the RESET study will operate with an exception from informed consent, or EFIC. This means patients will automatically be enrolled due to the life-threatening nature of the emergency, and then the patient or a family member can give consent to be part of the study after the fact.
“There’s actually not any time to go find family and walk them through the consent process and get them to sign and then talk to the investigational pharmacy about sending up the drug,” Foreman said. “All of that stuff can take an hour, and someone can’t seize for an hour. It’s really, really detrimental to their health.”
Even after receiving the drug in the emergency department, patients can withdraw consent to be part of the study going forward. Community members who wish to opt out of the study proactively by requesting an opt-out bracelet can learn more on the study’s website.
Featured photo at top of ambulance. Photo/Camilo Jimenez/Unsplash.
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