A Natural History Study of Angelman Syndrome (GLOW-AS)

A Longitudinal Natural History Study of Adults and Children With Angelman Syndrome

The goal of this observational study is to learn about the natural progression of Angelman syndrome (AS) in children and adults with a confirmed genetic diagnosis of AS. The main questions it aims to answer are:

• How do developmental skills, such as communication, motor abilities, and adaptive behaviors, change over a 1-year period in people with AS?
• Are there specific patterns in brain activity or sleep that are associated with changes in AS symptoms over time?

Participants will:

• Visit the study site 5 times over 1 year (approximately every 3 months) for assessments.
• Complete tests and questionnaires about development, behaviors, and sleep with the help of their caregivers.
• Undergo electroencephalograms (EEGs) to measure brain activity and wear a sleep-monitoring device at home (to collect actigraphy data).

Study Overview

• Status: Recruiting
• Conditions: Angelman Syndrome

Detailed Description

• Longitudinal, natural history study of 40 individuals with AS, enriched for an adolescent population.
• Seeks to establish normative data to inform future design and interpretation of clinical trials for AS and to support the development of more precise diagnostic tools and targeted therapeutic interventions for AS.
• Track adaptive behavior, communication, challenging behaviors, general health, overall disease severity, and common co-occurring conditions (including epilepsy and sleep disturbances) through standardized assessments.
• Biomarker data collected through EEGs and actigraphy recordings will be analyzed to assess age-related changes in clinical outcomes and neurophysiological measures.
• Participants will attend up to 5 in-person study visits over the course of 12 months: Week 0, Week 13, Week 26, Week 39, Week 52.

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

• Study Contact: Name: Leena Phan; Phone Number: 781-860-1711; Email: MGHGLOW-AS@mgb.org
• Study Contact Backup: Name: Caleb Weinstock; Phone Number: 781-860-1711; Email: MGHGLOW-AS@mgb.org

Study Locations

• United States
  • Massachusetts
    • Lexington, Massachusetts, United States, 02421
      • Recruiting
      • MGH Lurie Center for Autism
      • Principal Investigator: Christopher J Keary, MD
      • Sub-Investigator: Ronald L Thibert, DO, MSPH
      • Contact: Leena Phan; Phone Number: 781-860-1711; Email: MGHGLOW-AS@mgb.org
      • Contact: Caleb Weinstock; Phone Number: 781-860-1711; Email: MGHGLOW-AS@mgb.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Individuals who are at least 1 year of age with a genetically-confirmed diagnosis of AS.

Description

Inclusion Criteria:

• The participant has a primary clinical diagnosis of Angelman syndrome with documented genetic variation(s) affecting the function of the UBE3A gene within the human 15q11.2-q13.3 locus. Co-occurring conditions (e.g., autism spectrum disorder, cerebral palsy, intellectual disability) are permitted; however, Angelman syndrome must be the primary clinical diagnosis.
• The participant is male or female (assigned sex at birth) and aged ≥1 year at the initial study visit.
• The participant has a study partner who meets the study partner criteria below.
• The participant, if unable to provide informed consent, has an appropriate surrogate who is at least 18 years of age and willing and able to provide informed consent on behalf of the participant in accordance with current International Council for Harmonisation (ICH) guidelines and applicable institutional regulations.

Individuals must satisfy the following criteria to be enrolled as study partners:

• The study partner is a parent or primary caregiver who is at least 18 years of age.
• The study partner has consistent contact with the participant and, in the opinion of the investigator, is sufficiently knowledgeable about the participant's ongoing condition to provide accurate and current information.
• The study partner has sufficient English-language proficiency to complete study partner assessments.
• The study partner is willing and able to provide informed consent on their own behalf in accordance with ICH guidelines and applicable institutional regulations.
• The study partner is, in the opinion of the investigator, reliable and competent; willing and able to accompany the participant to all study visits and comply with study procedures; reachable by telephone or email as needed; and sufficiently knowledgeable about the participant's ongoing condition(s) to provide accurate and current information regarding the participant's health and well-being.

Exclusion Criteria:

• The participant has at least one additional known genetic abnormality outside the human 15q11.2-q13.3 locus causing a probable or known developmental disability.
• At least one standard-of-care treatment (medication or adjunctive therapy) used by the participant was changed during the 28 days (4 weeks) prior to the first study visit. Treatments include, but are not limited to, doses of anti-epileptic medications, behavioral management medications, sleep medications, gabapentin, cannabidiol, special diets, supplements, speech therapy, occupational therapy, applied behavioral analysis (ABA), psychosocial interventions, physical therapy, or nutritional support.
• The participant has unstable epilepsy, defined as having an emergency department visit or hospitalization for seizure-related concerns within the 28 days (4 weeks) preceding the initial study visit.
• The participant is of childbearing potential and is either pregnant, breastfeeding, or not using an adequate method of contraception; abstinence is acceptable.
• The participant has a clinically relevant history of malignancy; clinically significant abnormal test results; clinically significant cardiovascular, hematologic, hepatic, muscular, neurologic, or renal disease; or has experienced other clinical events which, in the opinion of the investigator, render participation unsuitable.
• The participant has a lifetime history of treatment with any cell- or gene-based therapy, including antisense oligonucleotides or gene-editing therapies.
• The participant has received any investigational therapy other than a cell- or gene-based therapy within 28 days or 5 half-lives (whichever is longer) preceding the initial study visit.
• The participant is currently enrolled or plans to enroll in an interventional study involving an investigational agent or device during the planned observation period.
• The participant has a known contraindication to electroencephalography, actigraphy, or any other study procedure described in the schedule of assessments.
• The participant or study partner is, in the opinion of the investigator, unsuitable for participation in any other way, including an inability to fulfill study requirements.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Participants aged 1-17 years (inclusive); Cohort 1: Participants aged at least 1 year old and less than 18 years old at the time of enrollment with genetically confirmed AS.; This cohort serves as the broad group for assessing the natural history of AS across childhood and adolescence.
Participants aged 1-12 years (inclusive); Cohort 2: Participants aged at least 1 year old and younger than 13 years old at the time of enrollment with genetically confirmed AS.; A subset of Cohort 1, specifically focused on preadolescents.; This cohort aims to capture developmental milestones and changes during a critical period of growth where potential therapeutic interventions may have the most significant impact.; Participants aged 1-12 years will first be assigned to Cohort 2 until its capacity is reached. Once Cohort 2 is full, participants aged 1-12 years will be enrolled in Cohort 1 only.
Participants aged 18 years and older; Cohort 3: Participants aged at least 18 years old.; This cohort is limited to up to 5 participants to explore the natural history of AS in adults, though it is not the primary focus of this study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Bayley Scale of Infant Development, Fourth Edition (Bayley-4) Cognitive Growth Score Equivalent at 12 Months	The Bayley-4 Cognitive subscale assesses cognitive development in children. Growth score equivalents are derived from developmental growth scale values (GSVs) that provide an equal-interval scale for measuring developmental change over time. Higher scores indicate greater cognitive development.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Bayley Scale of Infant Development, Fourth Edition (Bayley-4) Receptive Communication Growth Score Equivalent at 12 Months	The Bayley-4 Receptive Communication subscale assesses receptive language skills. Growth score equivalents are derived from developmental GSVs that provide an equal-interval scale for measuring developmental change over time. Higher scores indicate more advanced receptive communication abilities.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Bayley Scale of Infant Development, Fourth Edition (Bayley-4) Expressive Communication Growth Score Equivalent at 12 Months	The Bayley-4 Expressive Communication subscale assesses expressive language skills. Growth score equivalents are derived from developmental GSVs that provide an equal-interval scale for measuring developmental change over time. Higher scores indicate more developed expressive communication abilities.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Bayley Scale of Infant Development, Fourth Edition (Bayley-4) Fine Motor Growth Score Equivalent at 12 Months	The Bayley-4 Fine Motor subscale assesses fine motor skill development. Growth score equivalents are derived from developmental GSVs that provide an equal-interval scale for measuring developmental change over time. Higher scores indicate more developed fine motor skills.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Bayley Scale of Infant Development, Fourth Edition (Bayley-4) Gross Motor Growth Score Equivalent at 12 Months	The Bayley-4 Gross Motor subscale assesses gross motor skill development. Growth score equivalents are derived from developmental GSVs that provide an equal-interval scale for measuring developmental change over time. Higher scores indicate more developed gross motor skills.	Baseline, 3 months, 6 months, 9 months, and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Bayley Scale of Infant Development, Fourth Edition (Bayley-4) Cognitive Age-Equivalent Score at 12 Months	The Bayley-4 Cognitive subscale age-equivalent score represents the age in months at which the participant's raw score is the median score for typically developing children. Higher age-equivalent scores indicate more advanced cognitive development.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Bayley Scale of Infant Development, Fourth Edition (Bayley-4) Expressive Communication Age-Equivalent Score at 12 Months	The Bayley-4 Expressive Communication subscale age-equivalent score represents the age in months at which the participant's raw score is the median score for typically developing children. Higher age-equivalent scores indicate more advanced expressive communication abilities.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Bayley Scale of Infant Development, Fourth Edition (Bayley-4) Receptive Communication Age-Equivalent Score at 12 Months	The Bayley-4 Receptive Communication subscale age-equivalent score represents the age in months at which the participant's raw score is the median score for typically developing children. Higher age-equivalent scores indicate more advanced receptive communication abilities.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Bayley Scale of Infant Development, Fourth Edition (Bayley-4) Fine Motor Age-Equivalent Score at 12 Months	The Bayley-4 Fine Motor subscale age-equivalent score represents the age in months at which the participant's raw score is the median score for typically developing children. Higher age-equivalent scores indicate more advanced fine motor development.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Bayley Scale of Infant Development, Fourth Edition (Bayley-4) Gross Motor Age-Equivalent Score at 12 Months	The Bayley-4 Gross Motor subscale age-equivalent score represents the age in months at which the participant's raw score is the median score for typically developing children. Higher age-equivalent scores indicate more advanced gross motor development.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Symptoms of Angelman Syndrome-Clinical Global Impressions Scale of Severity (SAS-CGI-S) Global Severity Score at 12 Months	The SAS-CGI-S is a clinician-rated assessment of global symptom severity in Angelman syndrome. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients), with higher scores indicating greater global symptom severity.	Baseline, 3 months, 6 months, 9 months, 12 months
Change from Baseline in Aberrant Behavior Checklist-Community (ABC-C) Hyperactivity/Noncompliance Subscale Score (ABC-H) at 12 Months	The ABC-C Hyperactivity subscale assesses hyperactive and non-compliant behaviors. Scores range from 0 to 48, with higher scores indicating more severe hyperactivity symptoms.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Aberrant Behavior Checklist-Community (ABC-C) Irritability Subscale Score (ABC-I) at 12 Months	The ABC-C Irritability subscale assesses irritability, aggression, self-injury, and negative emotional states. Scores range from 0 to 45, with higher scores indicating more severe irritability symptoms.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Caregiver-Reported Angelman Syndrome Scale for Impact (CASS-I) Overall AS Symptoms Rating at 12 Months	The CASS-I is a caregiver-reported assessment of overall symptom severity and impact in Angelman syndrome. The scale provides a global rating of AS symptoms from the caregiver's perspective, with higher ratings indicating greater symptom severity and impact.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Children's Sleep Habits Questionnaire (CSHQ) Total Sleep Disturbance Score at 12 Months	The CSHQ is a parent-report questionnaire assessing sleep problems in children. The total score ranges from 33 to 99, with higher scores indicating greater sleep disturbance. A total score of 41 or higher indicates clinically significant sleep problems.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Children's Sleep Habits Questionnaire (CSHQ) Sleep Duration Subscale Score at 12 Months	The CSHQ Sleep Duration subscale assesses the adequacy of sleep duration. Higher scores indicate shorter or insufficient sleep duration.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Children's Sleep Habits Questionnaire (CSHQ) Night Wakings Subscale Score at 12 Months	The CSHQ Night Wakings subscale assesses the frequency and severity of nighttime awakenings. Higher scores indicate more frequent or problematic night wakings.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Observer-Reported Communication Ability (ORCA) Overall Communication T-Score at 12 Months	The ORCA is an observer-reported measure of communication abilities in individuals with Angelman syndrome. T-scores are standardized scores with a mean of 50 and standard deviation of 10. Higher t-scores indicate greater proficiency in overall communication abilities.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Observer-Reported Communication Ability (ORCA) Expressive Communication T-Score at 12 Months	The ORCA Expressive Communication subscale assesses expressive language abilities. T-scores are standardized scores with a mean of 50 and standard deviation of 10. Higher t-scores indicate greater proficiency in expressive communication.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Observer-Reported Communication Ability (ORCA) Receptive Communication T-Score at 12 Months	The ORCA Receptive Communication subscale assesses receptive language abilities. T-scores are standardized scores with a mean of 50 and standard deviation of 10. Higher t-scores indicate greater proficiency in receptive communication.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Observer-Reported Communication Ability (ORCA) Pragmatic Communication T-Score at 12 Months	The ORCA Pragmatic Communication subscale assesses social and contextual use of communication. T-scores are standardized scores with a mean of 50 and standard deviation of 10. Higher t-scores indicate greater proficiency in pragmatic communication.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Receptive Communication Age-Equivalent Score at 12 Months	The Vineland-3 Receptive Communication subdomain age-equivalent score represents the age in years and months at which the participant's score is typical for an average individual. Higher age-equivalent scores indicate more advanced receptive communication skills.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Receptive Communication Growth Score Equivalent at 12 Months	The Vineland-3 Receptive Communication GSV provides an equal-interval scale for measuring developmental change over time. Higher growth score equivalents indicate greater developmental progress in receptive communication.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Expressive Communication Age-Equivalent Score at 12 Months	The Vineland-3 Expressive Communication subdomain age-equivalent score represents the age in years and months at which the participant's score is typical for an average individual. Higher age-equivalent scores indicate more advanced expressive communication skills.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Expressive Communication Growth Score Equivalent at 12 Months	The Vineland-3 Expressive Communication subdomain GSV provides an equal-interval scale for measuring developmental change over time. Higher growth score equivalents indicate greater developmental progress in expressive communication.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Personal Daily Living Skills Age-Equivalent Score at 12 Months	The Vineland-3 Personal Daily Living Skills subdomain age-equivalent score represents the age in years and months at which the participant's score is typical for an average individual. Higher age-equivalent scores indicate more advanced personal daily living skills.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Personal Daily Living Skills Growth Score Equivalent at 12 Months	The Vineland-3 Personal Daily Living Skills subdomain GSV provides an equal-interval scale for measuring developmental change over time. Higher growth score equivalents indicate greater developmental progress in personal daily living skills.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Domestic Daily Living Skills Age-Equivalent Score at 12 Months	The Vineland-3 Domestic Daily Living Skills subdomain age-equivalent score represents the age in years and months at which the participant's score is typical for an average individual. Higher age-equivalent scores indicate more advanced domestic daily living skills.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Domestic Daily Living Skills Growth Score Equivalent at 12 Months	The Vineland-3 Domestic Daily Living Skills subdomain GSV provides an equal-interval scale for measuring developmental change over time. Higher growth score equivalents indicate greater developmental progress in domestic daily living skills.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Community Daily Living Skills Age-Equivalent Score at 12 Months	The Vineland-3 Community Daily Living Skills subdomain age-equivalent score represents the age in years and months at which the participant's score is typical for an average individual. Higher age-equivalent scores indicate more advanced community daily living skills.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Community Daily Living Skills Growth Score Equivalent at 12 Months	The Vineland-3 Community Daily Living Skills subdomain GSV provides an equal-interval scale for measuring developmental change over time. Higher growth score equivalents indicate greater developmental progress in community daily living skills.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Interpersonal Relationships Age-Equivalent Score at 12 Months	The Vineland-3 Interpersonal Relationships subdomain age-equivalent score represents the age in years and months at which the participant's score is typical for an average individual. Higher age-equivalent scores indicate more advanced interpersonal relationship skills.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Interpersonal Relationships Growth Score Equivalent at 12 Months	The Vineland-3 Interpersonal Relationships subdomain GSV provides an equal-interval scale for measuring developmental change over time. Higher growth score equivalents indicate greater developmental progress in interpersonal relationships.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Play and Leisure Time Age-Equivalent Score at 12 Months	The Vineland-3 Play and Leisure Time subdomain age-equivalent score represents the age in years and months at which the participant's score is typical for an average individual. Higher age-equivalent scores indicate more advanced play and leisure skills.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Play and Leisure Time Growth Score Equivalent at 12 Months	The Vineland-3 Play and Leisure Time subdomain GSV provides an equal-interval scale for measuring developmental change over time. Higher growth score equivalents indicate greater developmental progress in play and leisure skills.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Coping Skills Age-Equivalent Score at 12 Months	The Vineland-3 Coping Skills subdomain age-equivalent score represents the age in years and months at which the participant's score is typical for an average individual. Higher age-equivalent scores indicate more advanced coping skills.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Coping Skills Growth Score Equivalent at 12 Months	The Vineland-3 Coping Skills subdomain GSV provides an equal-interval scale for measuring developmental change over time. Higher growth score equivalents indicate greater developmental progress in coping skills.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Gross Motor Skills Age-Equivalent Score at 12 Months	The Vineland-3 Gross Motor Skills subdomain age-equivalent score represents the age in years and months at which the participant's score is typical for an average individual. Higher age-equivalent scores indicate more advanced gross motor skills.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Gross Motor Skills Growth Score Equivalent at 12 Months	The Vineland-3 Gross Motor Skills subdomain GSV provides an equal-interval scale for measuring developmental change over time. Higher growth score equivalents indicate greater developmental progress of gross motor skills.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Fine Motor Skills Age-Equivalent Score at 12 Months	The Vineland-3 Fine Motor Skills subdomain age-equivalent score represents the age in years and months at which the participant's score is typical for an average individual. Higher age-equivalent scores indicate more advanced fine motor skills.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Fine Motor Skills Growth Score Equivalent at 12 Months	The Vineland-3 Fine Motor Skills subdomain GSV provides an equal-interval scale for measuring developmental change over time. Higher growth score equivalents indicate greater developmental progress in fine motor skills.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Frequency of Reported Seizure Events at 12 Months	Seizure frequency is assessed through caregiver-reported seizure diaries documenting the number and type of seizure events over each measurement period. Seizure counts are analyzed as rates to account for variability in the duration of time covered by seizure diaries. Lower seizure rates indicate decreased seizure frequency.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Average Total Sleep Time Measured by Actigraphy at 12 Months	Total sleep time is the total amount of sleep obtained during the sleep period as measured by actigraphy, expressed in minutes. Higher values indicate longer sleep duration.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Average Effective Sleep Measured by Actigraphy at 12 Months	Effective sleep is the percentage of time asleep during the sleep period as measured by actigraphy. Values range from 0% to 100%, with higher percentages indicating more consolidated sleep.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Average Sleep Efficiency Measured by Actigraphy at 12 Months	Sleep efficiency is the ratio of total sleep time to time in bed, expressed as a percentage. Values range from 0% to 100%, with higher percentages indicating greater sleep efficiency.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Average Number of Nocturnal Awakenings Measured by Actigraphy at 12 Months	Nocturnal awakenings are the number of times a participant awakens during the sleep period as measured by actigraphy. Lower values indicate fewer sleep disruptions.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Average Duration of Nocturnal Awakenings Measured by Actigraphy at 12 Months	Duration of nocturnal awakenings is the average length of time spent awake during the sleep period as measured by actigraphy, expressed in minutes. Lower values indicate shorter awakening durations.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Average Sleep Onset Latency Measured by Actigraphy at 12 Months	Sleep onset latency is the time from attempting to sleep to the onset of sleep as measured by actigraphy, expressed in minutes. Lower values indicate faster sleep onset.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Average Total Sleep Time Reported in Sleep Diaries at 12 Months	Total sleep time as reported in caregiver-completed sleep diaries, representing the total amount of sleep the participant obtained during the sleep period, expressed in minutes. Higher values indicate longer sleep duration.	Baseline, 3 months, 6 months, 9 months, and 12 months
Change from Baseline in Average Duration of Nocturnal Awakenings Reported in Sleep Diaries at 12 Months	Duration of nocturnal awakenings as reported in caregiver-completed sleep diaries, representing the average length of time the participant spent awake during the sleep period, expressed in minutes. Lower values indicate shorter awakening durations.	Baseline, 3 months, 6 months, 9 months, and 12 months

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Astellas Pharma Global Development, Inc.
• Investigators: Principal Investigator: Christopher J Keary, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2029

Study Registration Dates

• First Submitted: February 11, 2026
• First Submitted That Met QC Criteria: February 11, 2026
• First Posted (Actual): February 18, 2026

Study Record Updates

• Last Update Posted (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: May 15, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Angelman syndrome; Angelman; AS; GLOW-AS
• Additional Relevant MeSH Terms: Imprinting Disorders; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Congenital Abnormalities; Movement Disorders; Abnormalities, Multiple; Chromosome Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Angelman Syndrome
• Other Study ID Numbers: 2025P003327

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to externally share IPD at this time, due to considerations regarding participant privacy, the risk of reidentification given the size and vulnerability of the study population, and limitations in the consent materials and protocol, which do not currently permit external data sharing. Institutional policy requires specific Data Use Agreements (DUAs) for any data sharing activity, and the study is protected by a Certificate of Confidentiality, further restricting disclosure of identifiable information. The research team may consider sharing de-identified data in the future, contingent upon publication of results and implementation of robust governance and approval mechanisms.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No