Use of Exogenous Ketones as a Nutritional Approach for Patients with Angelman Syndrome: Early Results of a Randomized Control Trial
Abstract number :
986
Submission category :
7. Antiepileptic Drugs / 7B. Clinical Trials
Year :
2020
Submission ID :
2423319
Source :
www.aesnet.org
Presentation date :
12/7/2020 1:26:24 PM
Published date :
Nov 21, 2020, 02:24 AM
Authors :
Robert Carson, Vanderbilt University Medical Center; Donna Herber - TruMacro; Alexandra Key - Vanderbilt University; Fenna Phibbs - Vanderbilt University Medical Center; Patience Ergish - Vanderbilt University Medical Center; Jessica Duis - Childrens Hosp
Rationale:
Angelman syndrome (AS) is a rare neurodevelopmental disorder present in approximately 1/15,000 individuals. It is caused by the absent expression of the maternal copy of the gene ubiquitin-protein ligase E3A (UBE3A). Individuals with AS present with developmental delay, gait ataxia, tremulous limbs, and unique behavioral characteristics including happy demeanor that includes frequent laughter, hyperactivity, and excitability. These individuals often have drug-resistant epilepsy, particularly those with a deletion at chromosome 15q11.2q13. Data suggests that diets promoting a metabolic transition to ketones are successful in managing seizures. We studied the use of an exogenous ketone supplement in patients with different diet backgrounds in a randomized, double-blind placebo-controlled crossover study.
Method:
Recruitment commenced from November 2018 to January 2020 for participants with molecularly confirmed AS in a study focused on safety and tolerability. We successfully enrolled 13 patients who completed the entirety of the study. Patients were initially enrolled and completed a medical history intake and evaluations including electroencephalogram (EEG), event-related potentials (ERP), gait analysis, Vineland-3, Developmental-Behavioral Checklists, Callier-Azusa mobility scale, lab work (comprehensive metabolic panel, CBC, lipid panel, acetoacetate level, and beta-hydroxybutyrate), daily urine ketostix, diaries of bowel habits, seizures, and diet throughout the study. Patients were provided with in-home EarlySenseÒ remote sleep monitoring devices. In-person visits included a visit at baseline (2 weeks), intervention (total 4 weeks), and placebo (total 4 weeks) visits with a 4-week washout period separating the intervention and placebo arms.
Results:
The active intervention was well-tolerated. The study had a high rate of drop out, with 21 patients completing an initial visit who withdrew due to the time commitment of the study. One patient withdrew due to distaste for the formulation and difficulty with consistent compliance with consumption. Preliminary EEG results showed a reduction in the relative delta power of the treatment group with a 5% difference without statistical significance (p=0.1683). Ten patients had a decrease in delta power when going from baseline to treatment. In 7/13, there was a decrease in the treatment group when compared to placebo. ERP data suggested active intervention was associated with an increase in the memory response at the frontal cluster. No statistical significance was achieved in review of blood and urine ketones. There was a suggestive improvement in constipation and hyperphagia.
Conclusion:
These data suggest that a nutritional intervention with exogenous ketones provides benefit for patients with AS, including those consuming a standard American diet. Suggestive benefits of nutritional ketosis included many features of AS beyond seizures, including cognition and bowel habits. A higher-powered study and more research are needed to confirm the results of this small study.
Funding:
:Foundation for Angelman Syndrome Therapeutics
Antiepileptic Drugs