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Trial record 1 of 1 for:    ketogenic | Angelman Syndrome
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Nutritional Formulation for Angelman Syndrome (FANS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03644693
Recruitment Status : Completed
First Posted : August 23, 2018
Last Update Posted : August 20, 2020
Sponsor:
Information provided by (Responsible Party):
University of Colorado, Denver

Tracking Information
First Submitted Date  ICMJE August 13, 2018
First Posted Date  ICMJE August 23, 2018
Last Update Posted Date August 20, 2020
Actual Study Start Date  ICMJE November 1, 2018
Actual Primary Completion Date January 15, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 21, 2018)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 21, 2018)
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Nutritional Formulation for Angelman Syndrome
Official Title  ICMJE Evaluation of the Safety and Tolerability of a Nutritional Formulation in Angelman Syndrome
Brief Summary 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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE 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).
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Other
Condition  ICMJE Angelman Syndrome
Intervention  ICMJE
  • 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.
  • 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.
Study Arms  ICMJE
  • Experimental: Investigational
    Subjects assigned to this arm will receive the Nutritional Formulation containing exogenous ketones.
    Intervention: Dietary Supplement: Nutritional Formulation Containing Exogenous Ketones
  • Placebo Comparator: Placebo
    Subjects assigned to this arm will receive the Placebo Formulation.
    Intervention: Dietary Supplement: Placebo Formulation
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 21, 2018)
15
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE January 15, 2020
Actual Primary Completion Date January 15, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 4 Years to 11 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03644693
Other Study ID Numbers  ICMJE 20-0366
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Colorado, Denver
Study Sponsor  ICMJE University of Colorado, Denver
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jessica Duis, MD, MS Children's Hospital Colorado
PRS Account University of Colorado, Denver
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP