by Jessica Pasley
A clinic at Monroe Carell Jr. Children’s Hospital at Vanderbilt is the first site for an international clinical trial for a nutritional intervention for patients with Angelman syndrome.
The trial, currently enrolling patients to a 16-week study period, will assess the benefits of using an exogenous ketone supplement in the management of Angelman syndrome symptoms, said the principal investigator, Jessica Duis, MD, MS, assistant professor of Pediatrics at Children’s Hospital.
“There is a significant unmet need for targeted nutritional support for Angelman syndrome patients that could serve as an adjunct therapy for the management of refractory seizures,” said Duis. “We expect this study will generate important insights about ketogenic diets and how they can benefit Angelman syndrome patients.
“A lot of our families are very interested in learning how to improve the quality of life of their children using exogenous ketones as a dietary intervention, which could allow them the ability to liberalize their child’s diet.”
Angelman syndrome is a complex, genetic disorder that primarily affects the nervous system. Characteristic features include delayed development, intellectual disability, severe speech impairment, problems with movement and balance and seizures.
Some children with treatment-resistant seizures are often prescribed a special dietary intervention, most commonly a ketogenic or low glycemic index therapy. These low-carb/high-fat diets are a natural way to transition the brain to alternate sources of energy, which may decrease the excitability of the brain, which could minimize seizure activity.
Duis said the trial, funded by a two-year, $250,000 grant from the Foundation for Angelman’s Syndrome Thera- peutics, has already enrolled seven patients. Children’s Hospital hopes to recruit 20 patients at this site.
The study is for patients ages 4-11 and will include three visits.
All participants will take part in a two-week collection of baseline data leading up to the first four-week intervention (placebo versus study formulation), followed by a four-week washout period.
During the second arm of the study, the patients will complete another four-week intervention, followed by a two-week washout period.
Neither study participants nor investigators know which patients will receive the placebo or the actual nutritional supplement.
“The really great thing about this study is that all of our patients will receive the actual formulation either in the first intervention or the second,” said Duis. “We will measure and collect data during the various clinic visits, and parents will also monitor sleep patterns, seizure activity, GI symptoms and keep a food diary at home.”
Duis plans to open study sites in Australia, with Vanderbilt serving as the coordinating center for the global trial.
“Even though we have improved the diagnostic ability to recognize Angelman syndrome, there have not been many trials focused on the disorder,” said Duis.
“We are now seeing more trials and a greater interest in impacting medical treatment of this rare condition in which individuals have hugely unmet medical needs. We hope to be able to bring more practical dietary interventions to a variety of patient populations.”