Angelman SyndromeGLOW-ASNCT07417137
A Natural History Study of Angelman Syndrome
An observational study of Angelman Syndrome and Neurodevelopmental Conditions, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 1 year and older
- Conditions the study is for
- Angelman Syndrome, Neurodevelopmental Conditions
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Sep 2026to Sep 2029
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 1 year and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Individuals who are at least 1 year of age with a genetically-confirmed diagnosis of AS.
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
MGH Lurie Center for Autism
Lexington, Massachusetts, 02421
Riley Shubb, 781-860-1711, MGHGLOW-AS@mgb.org
Leena Phan, 781-860-1711, MGHGLOW-AS@mgb.org
About this study
Official title: 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?
Read more
Participants will:
- Attend 3 in-person and 2 virtual study visits over 1 year 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).
Read the detailed description
- Longitudinal, natural history study of 40 individuals with AS, enriched for a child and 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 study visits over the course of 12 months: Week 0, Week 13, Week 26, Week 39, Week 52. Weeks 0, 26, 52 will be in-person. Weeks 13 and 39 will be remote.
- Conditions
- Angelman Syndrome, Neurodevelopmental Conditions
- Keywords
- Angelman syndrome, Angelman, GLOW-AS, AS, Natural History, Sleep
- Medical subject headings
- Angelman Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Week 0, Week 26, Week 52
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.
Measured: Week 0, Week 26, Week 52
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.
Measured: Week 0, Week 26, Week 52
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.
Measured: Week 0, Week 26, Week 52
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.
Measured: Week 0, Week 26, Week 52
Secondary outcomes (45)
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.
Measured: Week 0, Week 26, Week 52
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.
Measured: Week 0, Week 26, Week 52
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.
Measured: Week 0, Week 26, Week 52
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.
Measured: Week 0, Week 26, Week 52
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.
Measured: Week 0, Week 26, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
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.
Measured: Week 0, Week 13, Week 26, Week 39, Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2026
- Study start9 Sep 2026
- Primary completionSep 2028 (estimated)
- Study completionSep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Angelman SyndromeStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Astellas Pharma Global Development, Inc.
- Responsible party
- Principal investigator, Christopher Keary, Massachusetts General Hospital
- Investigators
- Christopher J Keary, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07417137
- Sponsor's protocol ID
- 2025P003327
- Acronym
- GLOW-AS
- Status last verified
- Oct 2026
- First submitted
- 11 Feb 2026
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: 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.
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Longitudinal Natural History Study of Adults and Children With Angelman Syndrome
- ClinicalTrials.gov ID
- NCT07417137
- Acronym / sponsor ID
- GLOW-AS / 2025P003327
- Conditions
- Angelman Syndrome, Neurodevelopmental Conditions
- Keywords
- Angelman syndrome, Angelman, GLOW-AS, AS, Natural History, Sleep
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Astellas Pharma Global Development, Inc.
- Study start
- 9 Sep 2026 (actual)
- Primary completion
- Sep 2028 (estimated)
- Study completion
- Sep 2029 (estimated)
- First posted
- 18 Feb 2026 (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.
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:
- Attend 3 in-person and 2 virtual study visits over 1 year 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).
Detailed description
- Longitudinal, natural history study of 40 individuals with AS, enriched for a child and 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 study visits over the course of 12 months: Week 0, Week 13, Week 26, Week 39, Week 52. Weeks 0, 26, 52 will be in-person. Weeks 13 and 39 will be remote.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 1 year and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Individuals who are at least 1 year of age with a genetically-confirmed diagnosis of AS.
Key inclusion criteria (10 listed)
- 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.
- The study partner is a parent or primary caregiver who is at least 18 years of age.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Change from Baseline in Bayley Scale of Infant Development, Fourth Edition (Bayley-4) Cognitive Growth Score Equivalent at 12 Months
Time frame: Week 0, Week 26, Week 52
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.
Change from Baseline in Bayley Scale of Infant Development, Fourth Edition (Bayley-4) Receptive Communication Growth Score Equivalent at 12 Months
Time frame: Week 0, Week 26, Week 52
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.
Change from Baseline in Bayley Scale of Infant Development, Fourth Edition (Bayley-4) Expressive Communication Growth Score Equivalent at 12 Months
Time frame: Week 0, Week 26, Week 52
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.
Change from Baseline in Bayley Scale of Infant Development, Fourth Edition (Bayley-4) Fine Motor Growth Score Equivalent at 12 Months
Time frame: Week 0, Week 26, Week 52
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.
Change from Baseline in Bayley Scale of Infant Development, Fourth Edition (Bayley-4) Gross Motor Growth Score Equivalent at 12 Months
Time frame: Week 0, Week 26, Week 52
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.
45 secondary outcomes
Change from Baseline in Bayley Scale of Infant Development, Fourth Edition (Bayley-4) Cognitive Age-Equivalent Score at 12 Months
Time frame: Week 0, Week 26, Week 52
Change from Baseline in Bayley Scale of Infant Development, Fourth Edition (Bayley-4) Expressive Communication Age-Equivalent Score at 12 Months
Time frame: Week 0, Week 26, Week 52
Change from Baseline in Bayley Scale of Infant Development, Fourth Edition (Bayley-4) Receptive Communication Age-Equivalent Score at 12 Months
Time frame: Week 0, Week 26, Week 52
Change from Baseline in Bayley Scale of Infant Development, Fourth Edition (Bayley-4) Fine Motor Age-Equivalent Score at 12 Months
Time frame: Week 0, Week 26, Week 52
Change from Baseline in Bayley Scale of Infant Development, Fourth Edition (Bayley-4) Gross Motor Age-Equivalent Score at 12 Months
Time frame: Week 0, Week 26, Week 52
Change from Baseline in Symptoms of Angelman Syndrome-Clinical Global Impressions Scale of Severity (SAS-CGI-S) Global Severity Score at 12 Months
Time frame: Week 0, Week 13, Week 26, Week 39, Week 52
Change from Baseline in Aberrant Behavior Checklist-Community (ABC-C) Hyperactivity/Noncompliance Subscale Score (ABC-H) at 12 Months
Time frame: Week 0, Week 13, Week 26, Week 39, Week 52
Change from Baseline in Aberrant Behavior Checklist-Community (ABC-C) Irritability Subscale Score (ABC-I) at 12 Months
Time frame: Week 0, Week 13, Week 26, Week 39, Week 52
Change from Baseline in Caregiver-Reported Angelman Syndrome Scale for Impact (CASS-I) Overall AS Symptoms Rating at 12 Months
Time frame: Week 0, Week 13, Week 26, Week 39, Week 52
Change from Baseline in Children's Sleep Habits Questionnaire (CSHQ) Total Sleep Disturbance Score at 12 Months
Time frame: Week 0, Week 13, Week 26, Week 39, Week 52
Change from Baseline in Children's Sleep Habits Questionnaire (CSHQ) Sleep Duration Subscale Score at 12 Months
Time frame: Week 0, Week 13, Week 26, Week 39, Week 52
Change from Baseline in Children's Sleep Habits Questionnaire (CSHQ) Night Wakings Subscale Score at 12 Months
Time frame: Week 0, Week 13, Week 26, Week 39, Week 52
Change from Baseline in Observer-Reported Communication Ability (ORCA) Overall Communication T-Score at 12 Months
Time frame: Week 0, Week 13, Week 26, Week 39, Week 52
Change from Baseline in Observer-Reported Communication Ability (ORCA) Expressive Communication T-Score at 12 Months
Time frame: Week 0, Week 13, Week 26, Week 39, Week 52
Change from Baseline in Observer-Reported Communication Ability (ORCA) Receptive Communication T-Score at 12 Months
Time frame: Week 0, Week 13, Week 26, Week 39, Week 52
Change from Baseline in Observer-Reported Communication Ability (ORCA) Pragmatic Communication T-Score at 12 Months
Time frame: Week 0, Week 13, Week 26, Week 39, Week 52
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Receptive Communication Age-Equivalent Score at 12 Months
Time frame: Week 0, Week 13, Week 26, Week 39, Week 52
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Receptive Communication Growth Score Equivalent at 12 Months
Time frame: Week 0, Week 13, Week 26, Week 39, Week 52
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Expressive Communication Age-Equivalent Score at 12 Months
Time frame: Week 0, Week 13, Week 26, Week 39, Week 52
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Expressive Communication Growth Score Equivalent at 12 Months
Time frame: Week 0, Week 13, Week 26, Week 39, Week 52
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Personal Daily Living Skills Age-Equivalent Score at 12 Months
Time frame: Week 0, Week 13, Week 26, Week 39, Week 52
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Personal Daily Living Skills Growth Score Equivalent at 12 Months
Time frame: Week 0, Week 13, Week 26, Week 39, Week 52
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Domestic Daily Living Skills Age-Equivalent Score at 12 Months
Time frame: Week 0, Week 13, Week 26, Week 39, Week 52
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Domestic Daily Living Skills Growth Score Equivalent at 12 Months
Time frame: Week 0, Week 13, Week 26, Week 39, Week 52
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Community Daily Living Skills Age-Equivalent Score at 12 Months
Time frame: Week 0, Week 13, Week 26, Week 39, Week 52
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Community Daily Living Skills Growth Score Equivalent at 12 Months
Time frame: Week 0, Week 13, Week 26, Week 39, Week 52
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Interpersonal Relationships Age-Equivalent Score at 12 Months
Time frame: Week 0, Week 13, Week 26, Week 39, Week 52
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Interpersonal Relationships Growth Score Equivalent at 12 Months
Time frame: Week 0, Week 13, Week 26, Week 39, Week 52
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Play and Leisure Time Age-Equivalent Score at 12 Months
Time frame: Week 0, Week 13, Week 26, Week 39, Week 52
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Play and Leisure Time Growth Score Equivalent at 12 Months
Time frame: Week 0, Week 13, Week 26, Week 39, Week 52
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Coping Skills Age-Equivalent Score at 12 Months
Time frame: Week 0, Week 13, Week 26, Week 39, Week 52
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Coping Skills Growth Score Equivalent at 12 Months
Time frame: Week 0, Week 13, Week 26, Week 39, Week 52
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Gross Motor Skills Age-Equivalent Score at 12 Months
Time frame: Week 0, Week 13, Week 26, Week 39, Week 52
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Gross Motor Skills Growth Score Equivalent at 12 Months
Time frame: Week 0, Week 13, Week 26, Week 39, Week 52
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Fine Motor Skills Age-Equivalent Score at 12 Months
Time frame: Week 0, Week 13, Week 26, Week 39, Week 52
Change from Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Fine Motor Skills Growth Score Equivalent at 12 Months
Time frame: Week 0, Week 13, Week 26, Week 39, Week 52
Change from Baseline in Frequency of Reported Seizure Events at 12 Months
Time frame: Week 0, Week 13, Week 26, Week 39, Week 52
Change from Baseline in Average Total Sleep Time Measured by Actigraphy at 12 Months
Time frame: Week 0, Week 13, Week 26, Week 39, Week 52
Change from Baseline in Average Effective Sleep Measured by Actigraphy at 12 Months
Time frame: Week 0, Week 13, Week 26, Week 39, Week 52
Change from Baseline in Average Sleep Efficiency Measured by Actigraphy at 12 Months
Time frame: Week 0, Week 13, Week 26, Week 39, Week 52
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2026.
- Individual participant dataSharing planned: No. 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.
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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.
Christopher J Keary, MD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Angelman Syndrome and Neurodevelopmental Conditions, run by Massachusetts General Hospital 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 10 inclusion and 10 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: looking for participants now, as of the sponsor's last update on 13 Oct 2026. 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. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Riley Shubb (781-860-1711, MGHGLOW-AS@mgb.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from Baseline in Bayley Scale of Infant Development, Fourth Edition (Bayley-4) Cognitive Growth Score Equivalent at 12 Months (time frame: Week 0, Week 26, Week 52). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Oct 2026.