Purpose

Low carbohydrate diets such as the ketogenic (KD) and low glycemic index (LGIT) diets have been shown to be effective in treating drug resistant seizures in children with Angelman syndrome (AS). The investigators hypothesize that consuming a fat based nutritional formulation with an exogenous ketone throughout the day will produce urinary ketosis in children consuming both low and high carbohydrate diets, depending upon dietary background. The nutritional formulation will provide fuel substrates that push metabolism away from carbohydrates and towards fat utilization. This research is being done to assess the safety and tolerability of a nutritional formulation for use in dietary interventions in AS.

Condition

Eligibility

Eligible Ages
Between 4 Years and 11 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Male or female
  • 4-11 years of age
  • Diagnosed with Angelman syndrome with prior lab report indicating genetic diagnosis
  • Currently on a LGIT, KD, or standard diet consistently for at least three months
  • Motivated to maintain the LGIT or KD for at least the duration of the trial period, as applicable
  • Written informed consent from patient and/or parent/caregiver
  • Willing to drink provided formulations, or to eat them mixed with food
  • Daytime toilet trained, or parents willing to use cotton balls in diapers to sample urine
  • Willing to test urine daily
  • Willing to comply with protocol examinations, including EEG, ERP, and venipuncture
  • Ambulatory, willing to perform gait tracking

Exclusion Criteria

  • Being pregnant or planning pregnancy
  • Requiring parenteral nutrition
  • Major hepatic or renal dysfunction
  • History of a diagnosis of diabetes
  • Participation in other clinical intervention studies within 1 month prior to entry of this study
  • Allergy to any of the study product ingredients
  • Investigator concern around willingness/ability of patient or parent/caregiver to comply with protocol requirements
  • Any contraindications for the use of the ketogenic or low carbohydrate diets
  • Significantly underweight (Body Mass Index <18.5)
  • Unwilling to drink provided formulations, or to consume formulation mixed with food
  • Not ambulatory, or unwilling to perform gait tracking
  • Not daytime toilet trained, or parents unwilling to use cotton balls in diapers to sample urine
  • Unwilling to test urine daily

Study Design

Phase
N/A
Study Type
Interventional
Allocation
Randomized
Intervention Model
Crossover Assignment
Intervention Model Description
The study design for this nutritional intervention protocol is a randomized, double blind, placebo controlled crossover study. Each patient will receive both nutritional formulation and placebo formulation, with a washout period between each arm. The dietary backgrounds will differ among patients. Acceptable diets include three basic diets: ketogenic diet (i.e. conventional 4:1 or 3:1, modified Atkins), low glycemic index diet (LGIT), and standard American diet (regular diet).
Primary Purpose
Other
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Investigational
Subjects assigned to this arm will receive the Nutritional Formulation containing exogenous ketones.
  • Dietary Supplement: Nutritional Formulation Containing Exogenous Ketones
    A nutritional formulation providing beta-hydroxybutyrate, 2g of carbohydrate, 1g of protein, and 9g of fat, plus minerals, per 100kcal. Given orally as food or beverage three times daily.
Placebo Comparator
Placebo
Subjects assigned to this arm will receive the Placebo Formulation.
  • Dietary Supplement: Placebo Formulation
    A placebo formulation providing similar amounts of carbohydrates, proteins and minerals as the nutritional formulation. Given orally as food or beverage three times daily.

Recruiting Locations

Vanderbilt University Medical Center
Nashville, Tennessee 37232
Contact:
Jessica Duis, MD, MS
615-343-3249
jessica.duis@vumc.org

More Details

NCT ID
NCT03644693
Status
Recruiting
Sponsor
Vanderbilt University Medical Center

Study Contact

Jessica Duis
(615) 343-3249
jessica.duis@vumc.org

Detailed Description

An evaluation of the safety and tolerability of a nutritional formulation in Angelman syndrome in children ages 4-11 years.

Study is conducted over 16 weeks:

2 week baseline period - Patient continues on current dietary regimen they were on before joining the study (standard, ketogenic, or LGIT).

4 week intervention period - Patient consumes either placebo or nutritional formulation for 4 weeks, maintaining their current diet.

4 week washout period - Patient continues on current dietary regimen without consuming any study formulations.

4 week intervention period - Patient consumes either placebo or nutritional formulation for 4 weeks (crossover), maintaining their current diet.

2 week washout period - Patient continues on current dietary regimen without consuming any study formulations.

Follow-up phone call to be conducted by study personnel during this time.

Data is captured by the investigator during baseline, intervention, and washout periods, and by the parent/caregiver daily throughout the protocol using apps loaded on a provided tablet.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.