Angelman SyndromeFANSNCT03644693
Nutritional Formulation for Angelman Syndrome
A study testing Nutritional Formulation Containing Exogenous Ketones in people with Angelman Syndrome, run by University of Colorado, Denver at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 4 to 11 years
- Conditions the study is for
- Angelman Syndrome
- What is being tested?
- Nutritional Formulation Containing Exogenous Ketones
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2018to 15 Jan 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 11 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
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- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hopsital Colorado
Aurora, Colorado, 80045
About this study
Official title: Evaluation of the Safety and Tolerability of a Nutritional Formulation in 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.
Read the 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.
- Conditions
- Angelman Syndrome
- Being tested
- Nutritional Formulation Containing Exogenous Ketones, Placebo Formulation
- Keywords
- Angelman Syndrome, Ketosis, Children
- Medical subject headings
- Angelman Syndrome, Ketosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nutritional Formulation Containing Exogenous KetonesDietary 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 FormulationDietary 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.
| Study group | Role | What they receive |
|---|---|---|
| Investigational | Experimental | Subjects assigned to this arm will receive the Nutritional Formulation containing exogenous ketones. Receives: Dietary Supplement: Nutritional Formulation Containing Exogenous Ketones |
| Placebo | Placebo comparator | Subjects assigned to this arm will receive the Placebo Formulation. Receives: Dietary Supplement: Placebo Formulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 16 weeks
Secondary outcomes (15)
Convenience, taste, and acceptability
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.
Measured: 16 weeks (measured 2 times)
Urinary Ketosis
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.
Measured: 16 weeks
Serum Ketosis
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.
Measured: 16 weeks (measured 3 times)
Number of Patients with Adverse Events
All adverse events will be monitored throughout the study. The number and type of adverse event will be recorded.
Measured: 16 weeks (measured 3 times)
Change in Mobility Measured Using Zeno Walkway
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.
Measured: 16 weeks (measured 3 times)
Change in Cognition as Measured by Event Related Potentials (ERP)
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.
Measured: 16 weeks (measured 3 times)
Change in Cortical Irritability Measured Using Electroencephalogram (EEG)
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.
Measured: 16 weeks (measured 3 times)
Number of Patients with Treatment Related Adverse Events as Assessed by Blood Metabolic Panel
Blood samples will be taken and assessed for complete blood count, comprehensive metabolic panel, ketones, and lipids.
Measured: 16 weeks (measured 3 times)
Nutrient Intake
Food diaries recorded daily to establish total caloric and macro-nutrient intake.
Measured: 16 weeks
Changes in Gastrointestinal (GI) Health
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.
Measured: 16 weeks
Changes in Sleep
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.
Measured: 16 weeks
Changes in Seizures
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.
Measured: 16 weeks
Height
Height (cm)
Measured: 16 weeks (measured 3 times)
Weight
Weight (kg)
Measured: 16 weeks (measured 3 times)
Change from Baseline in the Vineland Adaptive Behavior Score
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.
Measured: 16 weeks (measured 3 times)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2018
- Study start1 Nov 2018
- Primary completion15 Jan 2020
- Study completion15 Jan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Angelman SyndromeStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- 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 blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jessica Duis, MD, MS, Principal investigator, Children's Hospital Colorado
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03644693
- Sponsor's protocol ID
- 20-0366
- Acronym
- FANS
- Status last verified
- Aug 2020
- First submitted
- 13 Aug 2018
- Last updated
- 20 Aug 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 34510212Herber 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.
PubMed 31918761
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Safety and Tolerability of a Nutritional Formulation in Angelman Syndrome
- ClinicalTrials.gov ID
- NCT03644693
- Acronym / sponsor ID
- FANS / 20-0366
- Conditions
- Angelman Syndrome
- Keywords
- Angelman Syndrome, Ketosis, Children
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Study start
- 1 Nov 2018 (actual)
- Primary completion
- 15 Jan 2020 (actual)
- Study completion
- 15 Jan 2020 (actual)
- First posted
- 23 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- 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).
| Arm | Type | Receives |
|---|---|---|
| Investigational | Experimental | Dietary Supplement: Nutritional Formulation Containing Exogenous KetonesSubjects assigned to this arm will receive the Nutritional Formulation containing exogenous ketones. |
| Placebo | Placebo comparator | Dietary Supplement: Placebo FormulationSubjects assigned to this arm will receive the Placebo Formulation. |
Who may qualify
- Ages
- 4 to 11 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nutritional Formulation Containing Exogenous KetonesA 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 | Investigational |
| Placebo FormulationA placebo formulation providing similar amounts of carbohydrates, proteins and minerals as the nutritional formulation. Given orally as food or beverage three times daily. | Dietary supplement | Placebo |
Primary outcome
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.
15 secondary outcomes
Convenience, taste, and acceptability
Time frame: 16 weeks (measured 2 times)
Urinary Ketosis
Time frame: 16 weeks
Serum Ketosis
Time frame: 16 weeks (measured 3 times)
Number of Patients with Adverse Events
Time frame: 16 weeks (measured 3 times)
Change in Mobility Measured Using Zeno Walkway
Time frame: 16 weeks (measured 3 times)
Change in Cognition as Measured by Event Related Potentials (ERP)
Time frame: 16 weeks (measured 3 times)
Change in Cortical Irritability Measured Using Electroencephalogram (EEG)
Time frame: 16 weeks (measured 3 times)
Number of Patients with Treatment Related Adverse Events as Assessed by Blood Metabolic Panel
Time frame: 16 weeks (measured 3 times)
Nutrient Intake
Time frame: 16 weeks
Changes in Gastrointestinal (GI) Health
Time frame: 16 weeks
Changes in Sleep
Time frame: 16 weeks
Changes in Seizures
Time frame: 16 weeks
Height
Time frame: 16 weeks (measured 3 times)
Weight
Time frame: 16 weeks (measured 3 times)
Change from Baseline in the Vineland Adaptive Behavior Score
Time frame: 16 weeks (measured 3 times)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2020.
- Derived from this study: PubMed 34510212Carson 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.
- Derived from this study: PubMed 31918761Herber 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jessica Duis, MD, MS principal investigator
Children's Hospital Colorado
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Nutritional Formulation Containing Exogenous Ketones in people with Angelman Syndrome, run by University of Colorado, Denver at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Compliance with feeding protocol (time frame: 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03644693, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2020.