A clinical trial is evaluating the safety and tolerability of a nutritional formulation containing the ketone beta-hydroxybutyrate (BHB) as a treatment to help control seizures in children with Angelman syndrome.
More information about the trial, called Nutritional Formulation for Angelman Syndrome (FANS), is available here.
The protocol of this trial was described in a paper, titled “Evaluation of the safety and tolerability of a nutritional Formulation in patients with ANgelman Syndrome (FANS): study protocol for a randomized controlled trial,” published in the journal Trials.
Seizures that are resistant to medication are estimated to occur in more than three-quarters of people with Angelman syndrome (AS). Certain dietary interventions, the ketogenic diet in particular, have shown considerable efficacy at controlling these seizures. This diet involves eating very few carbohydrates (sugars and starches) and consuming more fats.
Generally, cells in the body will preferentially use carbohydrates — particularly glucose — as an energy source. When carbohydrates are unavailable, the body will instead use fat for energy in a process called ketosis. This process, in turn, generates molecules called ketones, such as BHB.
While it is not entirely known why ketones are beneficial, a number of hypotheses have suggested that ingesting ketones leads to a metabolic shift that results in increased inhibition of cell toxicity and ultimately to a dampening of overall neuron excitability and decreased seizure activity.
Although the “keto diet” can help control seizures, many people with AS experience digestive problems and difficulty in feeding, which make it difficult for them to adhere to the diet and get enough nutrition.
In the FANS trial, instead of going on a ketogenic diet, participants will be given a nutritional formulation that is directly supplemented with BHB. The idea is that directly consuming the ketones could produce similar benefits as a ketogenic diet, but be easier to manage.
The trial will be conducted in the Angelman Syndrome clinic at Monroe Carell Jr. Children’s Hospital at Vanderbilt University Medical Center (in Nashville, Tennessee) in collaboration with sponsor Disruptive Nutrition. The study is being funded by the Foundation for Angelman Syndrome Therapeutics (FAST).