A clinical study has began to enroll patients with Angelman syndrome to explore the safety and tolerability of a nutritional formula supplemented with ketones for use in dietary interventions.
This study is being conducted by Disruptive Nutrition, the keto-medical foods company subsidiary of Disruptive Enterprises, in collaboration with researchers at Monroe Carell Jr. Children’s Hospital at Vanderbilt and the University of South Florida. The study is being funded by a grant from the Foundation for Angelman Syndrome Therapeutics (FAST).
Ketones are natural compounds made when the body burns fat during caloric restriction, starvation, or when eating a low-carbohydrate (CHO) diet. These compounds can replace sugar as the main source of fuel for the body, with particular effects on the brain.
Ketone usage by the brain can improve its energy reserves, while protecting it from inflammation and oxidative stress — cellular damage as a consequence of high levels of oxidant molecules.
Dietary supplementation with ketones was shown to significantly decrease the frequency of seizures, improve behavior, learning, memory, and overall function in a mouse model of Angelman syndrome. These findings suggest that dietary ketone supplementation may hold potential to manage Angelman syndrome symptoms.
The trial (NCT03644693) plans to include approximately 15 children, ages 4-11, who have genetically confirmed Angelman syndrome and a variety of dietary backgrounds. Children will be randomly assigned to take a nutritional formulation containing exogenous ketones or a placebo dietary supplement for 16 weeks.
In the first two weeks of the study (baseline), children will continue on the normal dietary regimen they were on before joining the study — either standard diet, ketogenic, or low glycemic index (LGIT) diet.
In the next four weeks (intervention period), children will either receive a nutritional formulation containing exogenous ketones or a placebo formulation (given orally as food or beverage three times daily) while maintaining their normal diet.
The nutritional formulation consists of beta-hydroxybutyrate, 2 grams of carbohydrate, 1 gram of protein, and 9 grams of fat, plus minerals, per 100 kcal. The placebo formulation provides the same amount of carbohydrates, proteins and minerals as the nutritional formulation, but does not contain exogenous ketones.
This will be followed by a four-week washout period, when patients continue on their current dietary regimen without consuming any study formulations. Patients will then cross over (intervention group receives placebo, and vice versa) to the second four-week intervention period. The study will end with a two-week washout period.
Researchers will evaluate the safety of the nutritional formulation containing exogenous ketones and patients’ compliance with feeding protocol. They will also determine the children’s clinical status, assessed by changes in behavior, mobility, cognition, seizure frequency, gastrointestinal symptoms, and brain activity.
Data will be recorded by the investigator and by the parent/caregiver daily throughout the protocol, using apps downloaded on a provided tablet.
“We expect that this study will generate important insights about ketogenic diets and how they can benefit Angelman syndrome patients,” Jessica Duis, MD, MS, assistant professor of pediatrics at Children’s Hospital at Vanderbilt and principal investigator of the study, said in a press release.
“Initiation of this nutritional intervention represents a significant milestone for patients with Angelman syndrome, their caregivers and physicians,” said Donna Herber, PhD, chief science officer of Disruptive Enterprises. “This [new clinical] study demonstrates our continued commitment to improving societal wellbeing and scientific advancement of ketogenic technologies for nutritional support of Angelman syndrome and other medical conditions that would potentially benefit from a ketogenic diet.”
“We are excited to support this innovative clinical research study on a nutritional formulation containing exogenous ketones that would potentially transform the management of Angelman syndrome,” said Ed Weeber, PhD, professor at the College of Medicine of the University of South Florida.