Funded by a recent $17 million grant from the National Institutes of Health, Yale researchers will soon begin enrolling patients in the largest drug trial for childhood epilepsy conducted to date.
The study will focus on childhood absence epilepsy — also called petit mal — which accounts for 10 to 15 percent of all childhood epilepsy. This form of epilepsy is characterized by non-convulsive, extended periods of staring and is usually diagnosed in children in first or second grade.
While absence is the most common pediatric epilepsy, there are very few cases diagnosed annually. Candy Cardoza, research nurse coordinator of the study, said only about seven new-diagnosed children between the ages of two and 13 are expected to be enrolled in the study each year in Connecticut.
“In order to reach statistical significance, it’s estimated that between 450 and 500 children need to be enrolled,” said Edward Novotny Jr., associate professor of pediatrics, neurology and neurosurgery. “In order for us to see and identify enough children, we really had to go to the point of enrolling 20 centers.”
Yale University is one of a group of medical centers across the United States participating in the study, which will consist of concurrent trials of three anti-epileptic drugs. Two of the drugs are commonly used in epileptic children, and the third was more recently approved. At Yale, the study will be conducted through the General Clinical Research Center at Yale-New Haven Hospital. Novotny said new digital technology will facilitate the easy sharing of data among sites.
In addition to a standard drug trial, the study will examine the quality of life of children taking the drugs. Novotny said he expects the three drugs to demonstrate equal efficacy, but because they have differing side-effects including rash and liver problems, one may be more appropriate for certain individuals.
“Most children will be controlled with one of these three drugs,” Novotny said. “But what we don’t know is if some children do better with one of these three, and — what are the issues of side effects. What effect are [the drugs] going to have on a child’s learning ability and long term quality of life. Those aspects have never been studied.”
The study will also have a genetic component, researching possible genes that may signal which drugs are better suited to certain children and result in fewer side-effects, Novotny said.
The genetic component of the study will also address the fact that most children outgrow absence epilepsy by the time they reach adolescence. Only a relatively small percent of children with absence epilepsy develop adult epilepsy, also called “grand mal,” which is characterized by convulsions.
“They outgrow their risk of having seizures, which is interesting, because if they have an abnormality of the genes, as their body grows and their brain grows, other genes take over that function,” Novotny said. “It will be very interesting to understand that process.”
Additionally, the study consists of a neuropsychological component in which researchers will examine cognitive functions like memory and attention in children with absence epilepsy, said Michael Westerveld, associate professor of neurosurgery and pediatrics.
“This is the largest trial to study the cognitive domains that are most likely to be interrupted by these seizures,” Westerveld said. “The conventional wisdom is that these kids do okay, but people do recognize that there are learning disabilities that go along with absence epilepsy.”
Westerveld added that while children outgrow absence epilepsy, their learning disabilities remain. The neuropsychological part of the study aims, in part, to determine their association. Westerveld said he believes that absence epilepsy and learning disabilities are related.