Nutritional Formulation for Angelman Syndrome (FANS)
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|ClinicalTrials.gov Identifier: NCT03644693|
Recruitment Status : Completed
First Posted : August 23, 2018
Last Update Posted : August 20, 2020
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|Condition or disease||Intervention/treatment||Phase|
|Angelman Syndrome||Dietary Supplement: Nutritional Formulation Containing Exogenous Ketones Dietary Supplement: Placebo Formulation||Not Applicable|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||15 participants|
|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).|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Evaluation of the Safety and Tolerability of a Nutritional Formulation in Angelman Syndrome|
|Actual Study Start Date :||November 1, 2018|
|Actual Primary Completion Date :||January 15, 2020|
|Actual Study Completion Date :||January 15, 2020|
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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Nutrient Intake [ Time Frame: 16 weeks ]Food diaries recorded daily to establish total caloric and macro-nutrient intake.
- 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.
- 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.
- 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.
- Height [ Time Frame: 16 weeks (measured 3 times) ]Height (cm)
- Weight [ Time Frame: 16 weeks (measured 3 times) ]Weight (kg)
- 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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||4 Years to 11 Years (Child)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03644693
|United States, Colorado|
|Children's Hopsital Colorado|
|Aurora, Colorado, United States, 80045|
|Principal Investigator:||Jessica Duis, MD, MS||Children's Hospital Colorado|
|Responsible Party:||University of Colorado, Denver|
|Other Study ID Numbers:||
|First Posted:||August 23, 2018 Key Record Dates|
|Last Update Posted:||August 20, 2020|
|Last Verified:||August 2020|
|Studies a U.S. FDA-regulated Drug Product:||No|
|Studies a U.S. FDA-regulated Device Product:||No|
Central Nervous System Diseases
Nervous System Diseases
Genetic Diseases, Inborn