A Natural History Study of Angelman Syndrome

NCT07417137 | Recruiting

• 1 other identifier: 2025P003327
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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 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).

Conditions

Angelman Syndrome

Keywords

Angelman syndrome; Angelman; GLOW-AS; AS

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (45)

• Change from Baseline in Bayley Scale of Infant Development, Fourth Edition (Bayley-4) Cognitive Age-Equivalent Score at 12 Months

  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

  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

  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

  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

  Baseline, 3 months, 6 months, 9 months, and 12 months

Study Arms (3)

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.

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Astellas Pharma Global Development, Inc.: collaborator

Study Sites (1)

MGH Lurie Center for Autism

Lexington, Massachusetts, 02421, United States

RECRUITING

MeSH Terms

Conditions

Angelman Syndrome

Condition Hierarchy (Ancestors)

Movement Disorders; Central Nervous System Diseases; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Imprinting Disorders

Study Officials

• Christopher J Keary, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Caleb Weinstock

CONTACT

781-860-1711; MGHGLOW-AS@mgb.org

Leena Phan

CONTACT

781-860-1711; MGHGLOW-AS@mgb.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Behavioral Director (Angelman Syndrome Clinic) & Staff Psychiatrist (Lurie Center for Autism)

Study Record Dates

• First Submitted: February 11, 2026
• First Posted: February 18, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2029
• Last Updated: May 18, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)