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Completed

NCT Number: NCT03644693

Nutritional Formulation for Angelman Syndrome

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.

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Key information

Conditions

Angelman Syndrome Abnormalities, Multiple Acid-Base Imbalance Acidosis Central Nervous System Diseases Chromosome Disorders Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Imprinting Disorders Ketosis Metabolic Diseases Movement Disorders Nervous System Diseases Nutritional and Metabolic Diseases

Age range

4 year–11 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Children's Hopsital Colorado

Aurora, Colorado, 80045, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Nutritional Formulation Containing Exogenous Ketones

Dietary Supplement

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 formulation

Dietary Supplement

A placebo formulation providing similar amounts of carbohydrates, proteins and minerals as the nutritional formulation. Given orally as food or beverage three times daily.

Primary outcomes

  1. Compliance with feeding protocol

    Time frame: 16 weeks

    Tolerability will be demonstrated through patient compliance with the protocol as determined by the amount as measured in grams per day of nutritional formulation consumed as compared to the amount prescribed.

Secondary outcomes

  1. Convenience, taste, and acceptability

    Time frame: 16 weeks (measured 2 times)

    Parents/caregivers will rate convenience, taste, and acceptability of the nutritional formulation on a ten-point Likert scale. Each parameter will be rated individually with 1 = poor and 10 = excellent.

  2. Urinary Ketosis

    Time frame: 16 weeks

    The degree of nutritional ketosis will be evaluated in patients with different dietary backgrounds when consuming the nutritional formulation. Urine ketones will be recorded daily as mmol of acetoacetate.

  3. Serum Ketosis

    Time frame: 16 weeks (measured 3 times)

    The degree of nutritional ketosis will be evaluated in patients with different dietary backgrounds when consuming the nutritional formulation. Serum ketones will be recorded as mmol of R-beta-hydroxybutyrate.

  4. Number of Patients with Adverse Events

    Time frame: 16 weeks (measured 3 times)

    All adverse events will be monitored throughout the study. The number and type of adverse event will be recorded.

  5. Change in Mobility Measured Using Zeno Walkway

    Time frame: 16 weeks (measured 3 times)

    Patients with Angelman Syndrome typically have motor coordination and physical developmental delays resulting in an ataxic gate. As a measure of safety, the patient's gate characteristics for cadence will be compared to baseline.

  6. Change in Cognition as Measured by Event Related Potentials (ERP)

    Time frame: 16 weeks (measured 3 times)

    Patients with Angelman Syndrome have global severe intellectual disability. As a measure of safety, ERP waveform amplitude and timing in response to a presented stimuli will be compared to baseline.

  7. Change in Cortical Irritability Measured Using Electroencephalogram (EEG)

    Time frame: 16 weeks (measured 3 times)

    Patients with Angelman Syndrome have a characteristic EEG signature and are prone to seizure. As a measure of safety, the EEG signature will be compared to baseline in terms of the numbers of epileptiform discharges, notched delta and rhythmic theta activity.

  8. Number of Patients with Treatment Related Adverse Events as Assessed by Blood Metabolic Panel

    Time frame: 16 weeks (measured 3 times)

    Blood samples will be taken and assessed for complete blood count, comprehensive metabolic panel, ketones, and lipids.

  9. Nutrient Intake

    Time frame: 16 weeks

    Food diaries recorded daily to establish total caloric and macro-nutrient intake.

  10. Changes in Gastrointestinal (GI) Health

    Time frame: 16 weeks

    Patients with Angelman Syndrome frequently suffer from poor GI health. As a measure of safety, bowel movements will be characterized daily according to the Bristol Stool Chart and compared to baseline.

  11. Changes in Sleep

    Time frame: 16 weeks

    Patients with Angelman Syndrome frequently suffer from sleep issues. As a measure of safety, sleep duration and stage will be characterized by recording movement, heart rate and breathing during nighttime sleep and compared to baseline.

  12. Changes in Seizures

    Time frame: 16 weeks

    A significant percentage of Patients with Angelman Syndrome suffer from epileptic seizures. As a measure of safety, the number and type of seizures that occur will be recorded daily in a diary and compare to baseline.

  13. Height

    Time frame: 16 weeks (measured 3 times)

    Height (cm)

  14. Weight

    Time frame: 16 weeks (measured 3 times)

    Weight (kg)

  15. Change from Baseline in the Vineland Adaptive Behavior Score

    Time frame: 16 weeks (measured 3 times)

    Patients with Angelman Syndrome have severe global developmental delays. As a measure of safety, the Vineland Adaptive Behavior Scale, Third Edition will be used to measure changes from baseline in skills and independence.

Sponsors and collaborators

Lead sponsor

University of Colorado, Denver

Other

Registry information

Official study title

Evaluation of the Safety and Tolerability of a Nutritional Formulation in Angelman Syndrome

Acronym: FANS

Important dates

Study start
2018
Primary completion
2020
Study completion
2020
First posted
Aug 23, 2018
Registry last updated
Aug 20, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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