Nutritional Formulation for Angelman Syndrome

NCT03644693 | Completed DMC

• 1 other identifier: 20-0366
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Angelman Syndrome

Keywords

Angelman Syndrome; Ketosis; Children

Outcome Measures

Primary Outcomes (1)

• Compliance with feeding protocol

  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.

  16 weeks

Secondary Outcomes (15)

• Convenience, taste, and acceptability

  16 weeks (measured 2 times)

• Urinary Ketosis

  16 weeks

• Serum Ketosis

  16 weeks (measured 3 times)

• Number of Patients with Adverse Events

  16 weeks (measured 3 times)

• Change in Mobility Measured Using Zeno Walkway

  16 weeks (measured 3 times)

Study Arms (2)

Investigational

EXPERIMENTAL

Subjects assigned to this arm will receive the Nutritional Formulation containing exogenous ketones.

Dietary Supplement: Nutritional Formulation Containing Exogenous Ketones

Placebo

PLACEBO COMPARATOR

Subjects assigned to this arm will receive the Placebo Formulation.

Dietary Supplement: Placebo Formulation

Interventions

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.

Investigational

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.

Placebo

Eligibility Criteria

• Age: 4 Years - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male or female
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

Children's Hopsital Colorado

Aurora, Colorado, 80045, United States

Location

Related Publications (2)

• Carson RP, Herber DL, Pan Z, Phibbs F, Key AP, Gouelle A, Ergish P, Armour EA, Patel S, Duis J. Nutritional Formulation for Patients with Angelman Syndrome: A Randomized, Double-Blind, Placebo-Controlled Study of Exogenous Ketones. J Nutr. 2021 Dec 3;151(12):3628-3636. doi: 10.1093/jn/nxab284.

  PMID: 34510212 DERIVED

• Herber DL, Weeber EJ, D'Agostino DP, Duis J. Evaluation of the safety and tolerability of a nutritional Formulation in patients with ANgelman Syndrome (FANS): study protocol for a randomized controlled trial. Trials. 2020 Jan 9;21(1):60. doi: 10.1186/s13063-019-3996-x.

  PMID: 31918761 DERIVED

MeSH Terms

Conditions

Angelman Syndrome; Ketosis

Condition Hierarchy (Ancestors)

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

Study Officials

• Jessica Duis, MD, MS

  Children's Hospital Colorado

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: August 13, 2018
• First Posted: August 23, 2018
• Study Start: November 1, 2018
• Primary Completion: January 15, 2020
• Study Completion: January 15, 2020
• Last Updated: August 20, 2020

Record last verified: 2020-08

Locations

US (1)