Evaluation of the safety and tolerability of a nutritional Formulation in patients with ANgelman Syndrome (FANS): study protocol for a randomized controlled trial

Donna L Herber, Edwin J Weeber, Dominic P D'Agostino, Jessica Duis, Donna L Herber, Edwin J Weeber, Dominic P D'Agostino, Jessica Duis

Abstract

Background: Ketogenic and low-glycemic-index diets are effective in treating drug-resistant seizures in children with Angelman syndrome. Cognition, mobility, sleep, and gastrointestinal health are intrinsically linked to seizure activity and overall quality of life. Ketogenic and low-glycemic diets restrict carbohydrate consumption and stabilize blood glucose levels. The ketogenic diet induces ketosis, a metabolic state where ketone bodies are preferentially used for fuel. The use of exogenous ketones in promoting ketosis in Angelman syndrome has not been previously studied. The study formulation evaluated herein contains the exogenous ketone beta-hydroxybutyrate to rapidly shift the body towards ketosis, resulting in enhanced metabolic efficiency.

Methods/design: This is a 16-week, randomized, double-blind, placebo-controlled, crossover study to assess the safety and tolerability of a nutritional formula containing exogenous ketones. It also examines the potential for exogenous ketones to improve the patient's nutritional status which can impact the physiologic, symptomatic, and health outcome liabilities of living with Angelman syndrome.

Discussion: This manuscript outlines the rationale for a study designed to be the first to provide data on nutritional approaches for patients with Angelman syndrome using exogenous ketones.

Trial registration: ClinicalTrials.gov, ID: NCT03644693. Registered on 23 August 2018. Last updated on 23 August 2018.

Keywords: Angelman syndrome; Children; Exogenous ketone; Ketogenic diet; Ketone ester; Ketone supplement; Ketosis; Placebo-controlled trial.

Conflict of interest statement

DLH is employed by Disruptive Enterprises, LLC which has exclusively licensed the patents to the formula used in this study. EJW is an inventor on one of the patents covering the study formulation, has received research support from the Foundation for Angelman Syndrome Therapeutics, and is currently employed by PTC Therapeutics which engages in the development and commercialization of gene therapies for Angelman syndrome. DPD is an inventor on one of the patents covering the study formulation, and has received funding from Disruptive Enterprises, LLC and the Office of Naval Research. JD has received funding from the Foundation for Angelman Syndrome Therapeutics and the Angelman Syndrome Foundation.

Figures

Fig. 1
Fig. 1
FANS trial design – randomized, placebo-controlled, crossover study. Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) Figure; schedule of enrollment, interventions, and assessments. *May be conducted by telephone or in person at the clinic site. **An additional sample of blood will be collected during the baseline visit and added to a repository. Samples may be used for studies such as DNA and RNA, proteomics, and metabolomics and may be used for ancillary studies unrelated to the current trial. At the time of publication, no other studies have been planned

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