Angelman Syndrome Natural History Study-FAST UK

A Monocentric, Prospective, Longitudinal and Observational Natural History Study for Patients With Angelman Syndrome in the United Kingdom: Natural History - Foundation for Angelman Syndrome Therapeutics (FAST) United Kingdom (UK)

The goal of this study is to conduct a prospective, longitudinal assessment of the natural clinical progression of Angelman syndrome (AS) in children and adults. This will be performed by acquiring baseline measurements, and developing effective outcome measures and diagnostic tools for the syndrome, to prepare the healthcare system for forthcoming clinical trials.

Study Overview

• Status: Recruiting
• Conditions: Angelman Syndrome
• Intervention / Treatment: Other: Natural History Study

Detailed Description

This study is being conducted in anticipation of several candidate therapies which are approaching clinical readiness for Angelman syndrome. This study will comprehensively evaluate the natural clinical progression of the disease using scales and questionnaires for the assessment of motor function and global development, motor measuring devices (ActiMyo), and by collecting sleep and seizure diaries. In addition, proteomic analysis and electroencephalography (EEG) recordings will be collected to identify biomarkers which will indicate improvements in disease outcome following treatment.

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

Contacts and Locations

Study Locations

• United Kingdom
  • Oxon
    • Oxford, Oxon, United Kingdom, OX3 9DU
      • Recruiting
      • University of Oxford
      • Contact: Theodora Markati, MD, MPhil; Phone Number: 01865234220; Email: theodora.markati@paediatrics.ox.ac.uk
      • Contact: Corinne Betts, DPhil; Email: corinne.betts@paediatrics.ox.ac.uk
      • Principal Investigator: Laurent Servais, MD, PhD

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

• Genetically confirmed diagnosis of AS
• 0-99 years
• Male or Female

Description

Inclusion Criteria:

For the candidate participants affected by AS:

• Genetically confirmed diagnosis of AS
• 0-99 years
• Male or Female
• Obtained consent forms and/or record of consultation by the carers.

In this study, the two primary carers for each participant diagnosed with AS will be also considered participants. Carers will have to meet the following inclusion criteria:

• Male or Female
• >18 years
• Legal carer of the patient diagnosed with AS
• Willingness to follow study procedures, as assessed by the research team
• Willingness to sign the consent form
• Ability to understand all the information regarding the study, as assessed by the research team

Exclusion Criteria:

• The participant affected by AS may not enter the study if there is any comorbidity (*) that could potentially affect the results of the study. This will be subject to the clinical judgement of the Chief Investigator (CI) and/or the Principal Investigator (PI). Participants of ongoing (interventional) clinical trials that assess the efficacy of potential treatments will be excluded as assessments need to be done on the basis that represent the natural progression of AS.

(*) This includes any confirmed chronic or acute condition or disease affecting any system(s), which could interfere with the results of the study and/or the compliance with the study procedures.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Angelman syndrome patients; This study will comprehensively evaluate the natural clinical progression of the disease using scales and questionnaires for the assessment of motor function and global development, movement monitoring devices (ActiMyo), and by collecting sleep and seizure diaries. In addition, proteomic analysis and electroencephalography (EEG) recordings will be collected to identify biomarkers that will indicate improvements in disease outcome following treatment.

Other: Natural History Study; Longitudinal assessment of disease progression of Angelman syndrome in patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Collection of relevant medical data (retrospective and prospective)	Collection of demographic data, Angelman Syndrome-related medical history, past medical and surgical history, current medication, history of immunisations and family medical history.	2 years 1 month
Neurological assessment scale	Hammersmith Infant Neurological Examination (HINE) (0-2 years ONLY). Maximum global score of 78. Higher scores indicate a higher degree of neurological performance.	2 years 1 month
Clinical Scale	Clinical Global Impressions Scale - Angelman Syndrome version (CGI-SAS). Scales whereby practitioner rates from 1 to 7 the overall improvement/deterioration of the participant affected by Angelman Syndrome. One is improved and 7 denotes deterioration.	2 years 1 month
Clinical Scale	Caregiver-reported Angelman Syndrome Scale (CASS). Scales whereby the carer rates from 1 to 7 the overall improvement/deterioration of the participant affected to by Angelman Syndrome. One is improved and 7 denotes deterioration.	2 years 1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Movement monitoring using wearable device	Continuous movement monitoring using actimetry ActiMyo® in uncontrolled environment (i.e., home)	2 years 1 month
Gross motor milestones	World Health Organisation (WHO) Motor Milestones. Scale of 6 gross motor milestones. Lower scores denotes worse motor function.	2 years 1 month
Global development assessment scale	Bayley Scales of Infant and Toddler Development - 4 (BSID-4) for Developmental delays. Scale is divided into five domains, which are further divided into subdomains. The first step is to calculate the starting point by beginning with the items that are age appropriate. The starting point is validated if three consecutive items are achieved. If the participant affected by Angelman Syndrome does not achieve three consecutive items in a row at the age-appropriated starting point, the evaluator must go backwards to the lower age-starting point until the participant affected by Angelman Syndrome achieves three items in a row. The assessment stops once five items in a row are not achieved.	2 years 1 month
Global development assessment scale	Vineland Adaptive Behaviour Scales-III (VABS-III). Scale composed of two main domains, which are subdivided into several subdomains. Lower score indicates worse cognitive functioning.	2 years 1 month
Aberrant behaviour assessment	Aberrant Behaviour Checklist-Community (ABC-C). This scale comprises 58 items and is divided into five subdomains. The ABC-C is designed on a four-point scale with the lowest score representing less-affected patients while the highest score represents the severest patients.	2 years 1 month
Communication assessment	Observed Reported Communication Assessment (ORCA) Tool. Questionnaire designed to be completed by the patients' main carer and records patient communication.	2 years 1 month
Motor function assessment	Functional Mobility Scale (FMS). Scale which rates the walking ability in three different walking distances, and these distances will be rated on a 6-point scale.	2 years 1 month
Sleep and seizure activity	Sleep and seizure diaries with ready-made questionnaires	2 years 1 month
Laboratory biomarkers for Angelman syndrome	Proteomic analysis of plasma samples to determine biomarkers of disease progression	2 years 1 month
Electroencephalogram (EEG) activity recordings	Electroencephalogram (EEG) to record brain activity of Angelman Syndrome patients over a 24-hour period (e.g., sleep architecture, number and frequency of seizures, background epileptic activity, delta-rhythmicity)	24 hours
Quality of Life questionnaires for families of Angelman syndrome patients	PedsQL-Family Module questionnaires. Questionnaire uses ranking system of 1-4 based on frequency.	2 years 1 month
Quality of life assessment for individuals affected by Angelman syndrome	PedsQL-Core Module questionnaires. Questionnaire uses ranking system which depends on the age of patient.	2 years 1 month
Health economics	Interview with Carer's	2 years and 1 month
Clinical trial readiness	Demographic data collection and facilities preparation	2 years and 1 month

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
DNA biobank	Blood sample collection and DNA extraction and storage	2 years and 1 month

Collaborators and Investigators

• Sponsor: University of Oxford
• Collaborators: Hoffmann-La Roche; Foundation for Angelman Syndrome Therapeutics UK

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2021
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: August 13, 2021
• First Submitted That Met QC Criteria: October 19, 2021
• First Posted (Actual): October 29, 2021

Study Record Updates

• Last Update Posted (Estimated): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Natural History; EEG; outcome measures; proteomics; ActiMyo
• Additional Relevant MeSH Terms: Pathologic Processes; Central Nervous System Diseases; Nervous System Diseases; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Movement Disorders; Abnormalities, Multiple; Chromosome Disorders; Syndrome; Angelman Syndrome
• Other Study ID Numbers: PID15397

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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