NCT04812119

Brief Summary

The aim of this study is to explore and define the correlations between genotype and phenotype in patients with CTNNB1 mutations as well as monitor and survey the natural history of the CTNNB1 syndrome.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
100

participants targeted

Target at P50-P75 for all trials

Timeline
Completed

Started Mar 2021

Geographic Reach
2 countries

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2021

Completed
18 days until next milestone

First Submitted

Initial submission to the registry

March 19, 2021

Completed
4 days until next milestone

First Posted

Study publicly available on registry

March 23, 2021

Completed
1.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2022

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2022

Completed
Last Updated

November 2, 2022

Status Verified

November 1, 2022

Enrollment Period

1.5 years

First QC Date

March 19, 2021

Last Update Submit

November 1, 2022

Conditions

Keywords

CTNNB1 Gene MutationCTNNB1 SyndromeBeta-cateninAutism Spectrum DisorderDevelopmental delay

Outcome Measures

Primary Outcomes (1)

  • Baseline comprehensive collection of medical, behavioral, learning, and developmental information of patients who have documented CTNNB1 gene changes.

    Patients with a documented CTNNB1 gene change and/or their caretakers will report detailed medical and family history information and provide the results of genetic and other diagnostic testing by completing our online questionnaire. They will be guided through the questionnaire by the help of a medical doctor via an electronic meeting (Zoom) by one of our researchers. Online research surveys will be used to collect information about the patient's genotype and phenotype, with the goal of better understanding the diversity of CTNNB1 syndrome and thus improving clinical care and treatment for these patients.

    Baseline data is collected over the course of one month, on average.

Study Arms (1)

Patients with the CTNNB1 mutation

Patient with a diagnosed CTNNB1 mutation.

Diagnostic Test: The Modified Checklist for Autism in Toddlers, Revised with Follow-Up (M-CHAT-R/F)Diagnostic Test: The Autism Spectrum Quotient-Children's Version (AQ-Child)Diagnostic Test: The Autism-Spectrum Quotient (AQ)-Adolescent Version (AQ-Adolescent)Diagnostic Test: The Viking's Speech ScaleDiagnostic Test: The Functional Communication Classification System (FCCS)Diagnostic Test: Brief Infant Sleeping Questionnaire (BISQ)Diagnostic Test: Pediatric Sleep Questionnaire (PSQ)Diagnostic Test: The Eating and Drinking Ability Classification System (EDACS)Diagnostic Test: Mini Manual Ability Classification System (Mini-MACS)Diagnostic Test: Manual Ability Classification System (MACS)Diagnostic Test: The Gross Motor Function Classification System - Expanded and Revised (GMFCS - E&R)Diagnostic Test: The Visual Function Classification System (VFCS)Diagnostic Test: The Early Childhood Oral Health Impact Scale (ECOHIS)Diagnostic Test: The Family Impact Scale (FIS)Diagnostic Test: The Achenbach System of Empirically Based Assessment (ASEBA)Diagnostic Test: Adaptive Behavior Assessment System Third Edition (ABAS-3)

Interventions

The Modified Checklist for Autism in Toddlers, Revised with Follow-Up (M-CHAT-R/F; Robins, Fein, \& Barton, 2009) is a 2-stage parent-report screening tool to assess risk for Autism Spectrum Disorder (ASD). It is valid for children 16-30 months old.

Also known as: M-CHAT-R/F
Patients with the CTNNB1 mutation

The Autism Spectrum Quotient-Children's Version (AQ-Child; Auyeung, Baron-Cohen, Wheelwright \& Allison, 2008) is a parent-report questionnaire that aims to quantify autistic traits in children 4-11 years old. It contains 50 likert-type items with responses ranging from "definitely agree" to "definitely disagree".

Also known as: AQ-Child
Patients with the CTNNB1 mutation

The Autism Spectrum Quotient-Children's Version (AQ-Child; Auyeung, Baron-Cohen, Wheelwright \& Allison, 2008) is a parent-report questionnaire that aims to quantify autistic traits in children 12-15 years old. It contains 50 likert-type items with responses ranging from "definitely agree" to "definitely disagree".

Also known as: AQ-Adolescent
Patients with the CTNNB1 mutation

The Viking Speech Scale (Pennington, Virella, Mjøen, da Graça Andrada, Murray, Colver, … \& Andersen, 2013) is used to classify children's speech production, specifically the ease at which children can make themselves understood using different methods of communication. The scale has four levels and is ordinal. The four levels include: (1) speech is not affected by motor disorder (2) speech is imprecise but usually understandable to unfamiliar listeners (3) speech is unclear and not usually understandable to unfamiliar listeners out of context (3) no understandable speech. It is intended for children above the age of 4 years.

Patients with the CTNNB1 mutation

The Functional Communication Classification System (Barty, Caynes \& Johnston, 2016) was designed to classify how children with cerebral palsy communicate on a daily basis. The tool focuses on how children typically communicate with familiar and unfamiliar communication partners. There are five classifications a child can be categorized in: (1) effective communicator in most situations (2) effective communicator in most situations, but does need some help (3) an effective communicator in most situations and can communicate small ranges of messages and topics to most familiar people (4) assistance is required in most situations, especially with unfamiliar people and environments. Communicates daily needs and wants to familiar people (5) communicates using undirected movement, vocalisation and/or behaviour, for interpretation by familiar people. The FCCS is valid for use in children up to 13 years.

Also known as: FCCS
Patients with the CTNNB1 mutation

The Brief Infant Sleep Questionnaire (BISQ; Sadeh, 2004) is used to assess sleep patterns, parent perception, and sleep-related behaviors in young children (0-36 months). The BISQ has been validated against actigraphy, daily logs, and has high sensitivity in documenting expected developmental trends in sleep.

Also known as: BISQ
Patients with the CTNNB1 mutation

Pediatric Sleep Questionnaire (PSQ; Chervin, Hedger, Dillon, Pituch, 2000) has been designed to screen for sleep problems in children. The scale consists of 22 parent-reported items examining snoring and breathing problems, daytime sleepiness, inattention, hyperactivity, and other signs and symptoms of apnea including obesity and nocturnal enuresis. Those questions specifically relate to sleep-disordered breathing (SDB) in children. PSQ has been validated for children 2-18 years old.

Also known as: PSQ
Patients with the CTNNB1 mutation

The Eating and Drinking Ability Classification System (EDACS; Sellers, Mandy, Pennington, Hankins, Morris, 2013) has been developed for people with cerebral palsy to describe five distinct levels of ability using the key features of safety and efficiency. The patient can be categorized in: (1) eats and drinks safely and efficiently, (2) eats and drinks safely but with some limitations to efficiency, (3) eats and drinks with some limitations to safety; maybe limitations to efficiency, (4) eats and drinks with significant limitations to safety or (5) unable to eat or drink safely - tube feeding may be considered to provide nutrition. The EDACS is valid for use in children above the age of 36 months.

Also known as: EDACS
Patients with the CTNNB1 mutation

The Mini Manual Ability Classification System (Mini-MACS; Eliasson, Krumlinde-Sundholm, 2013) describes how children with cerebral palsy use their hands to handle objects in daily activities. MACS describes five levels. The levels are based on the children's self-initiated ability to handle objects and their need for assistance or adaptation to perform manual activities in everyday life. It has been validated for children 1-4 years of age.

Also known as: Mini-MACS
Patients with the CTNNB1 mutation

The Manual Ability Classification System (MACS; Eliasson, Krumlinde Sundholm, Rösblad, Beckung, Arner, Öhrvall, Rosenbaum, 2006) describes how children with cerebral palsy use their hands to handle objects in daily activities. MACS describes five levels. The levels are based on the children's self-initiated ability to handle objects and their need for assistance or adaptation to perform manual activities in everyday life. It has been validated for children 4-18 years.

Also known as: MACS
Patients with the CTNNB1 mutation

The Gross Motor Function Classification System - Expanded \& Revised (GMFCS - E\&R; Palisano, Rosenbaum, Bartlett, Livingston, 2007) is a 5-level classification system that describes the gross motor function of children and youth with cerebral palsy on the basis of their self-initiated movement with particular emphasis on sitting, walking, and wheeled mobility. Distinctions between levels are based on functional abilities, the need for assistive technology, including hand-held mobility devices (walkers, crutches, or canes) or wheeled mobility, and to a much lesser extent, quality of movement. The questionnaire is available for four age groups of children and youth: 2 to \< 4 years, 4 to \< 6 years, 6 to \< 12 years, and 12 to 18 years.

Also known as: GMFCS - E&R
Patients with the CTNNB1 mutation

The Visual Function Classification System (Baranello et al, 2019) is a valid and reliable 5-level classification system of visual functioning for children with Cerebral Palsy. It describes the use of visual abilities in daily life, focusing on activity and participation.

Also known as: VFCS
Patients with the CTNNB1 mutation

The ECOHIS measures the impact of oral problems and/or experience of dental treatment on the quality of life in children under 5 years old and their parents or other family members. It has 13 questions divided into two domains: one related to impact on the child (9 questions), and another to impact on the family (4 questions), measured using the Likert scale. In children with cerebral palsy and/or the ECOHIS has been validated for ages up to 6,5 years, in children with intellectual disability for ages up to 5 years and in children with special need for ages up to 9 years.

Also known as: ECOHIS
Patients with the CTNNB1 mutation

The FIS evaluates the impact of a child's oral condition on family life. It consists of 14 items divided into three subscales: parental/family activity (PA), parental emotions (PE), and family conflict (FC). The financial burden subscale (FB) is the only one that is evaluated separately, since it comprises a single item and addresses economic rather than psychosocial or behavioural impact. It has been validated for children above the age of 12 years.

Also known as: FIS
Patients with the CTNNB1 mutation

The Achenbach System of Empirically Based Assessment (ASEBA; Achenbach) is a collection of questionnaires used to assess adaptive and maladaptive behavior and overall functioning in individuals. The system includes report forms for multiple informants - the Child Behavior Checklist (CBCL) is used for caregivers to fill out ratings of their child's behavior, the Youth Self Report Form (YSR) is used for children to rate their own behavior, and the Teacher Report Form (TRF) is used for teachers to rate their pupil's behavior. The ASEBA seeks to capture consistencies or variations in behavior across different situations and with different interaction partners. The ASEBA exists for multiple age groups, including preschool-aged children, school-aged children, adults, and older adults. Scores for individuals in each age group are norm-referenced.

Also known as: ASEBA
Patients with the CTNNB1 mutation

The ABAS-3 (Harrison, Oakland, 2015) is a rating scale useful for assessing skills of daily living in individuals with developmental delays, autism spectrum disorder, intellectual disability, learning disabilities, neuropsychological disorders, and sensory or physical impairments. Rating forms are filled out by the parent and a teacher. The ABAS-3 covers three broad domains: conceptual, social, and practical, using 11 skill areas within these domains. Tasks focus on everyday activities required to function, meet environmental demands, care for oneself, and interact with others effectively and independently. On a 4-point response scale, raters indicate whether, and how frequently, the individual performs each activity.

Also known as: ABAS-3
Patients with the CTNNB1 mutation

Eligibility Criteria

Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

The study will enroll and collect data from people who have a diagnosed mutation in the CTNNB1 gene. Participants include people who have a gene change and at least one parent or guardian. Participants can also include multiple people who have a diagnosed CTNNB1 mutation and are within the same family.

You may qualify if:

  • Patients with a diagnosed mutation in the CTNNB1 gene.
  • Patients whose parents/caregivers were informed about the aims of the study and have signed the Informed consent form.

You may not qualify if:

  • Patients who do not have a diagnosed mutation in the CTTNB1 gene.
  • Patients whose caregivers have not signed the Informed consent form.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

The University of Sydney

Sydney, Australia

Location

Children's Medical Research Institute

Westmead, Australia

Location

University Medical Centre Ljubljana

Ljubljana, Slovenia

Location

MeSH Terms

Conditions

Autism Spectrum DisorderLearning Disabilities

Condition Hierarchy (Ancestors)

Child Development Disorders, PervasiveNeurodevelopmental DisordersMental DisordersCommunication DisordersNeurobehavioral ManifestationsNeurologic ManifestationsNervous System DiseasesSigns and SymptomsPathological Conditions, Signs and Symptoms

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
CROSS SECTIONAL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Assoc. Prof. Damjan Osredkar, MD, PhD

Study Record Dates

First Submitted

March 19, 2021

First Posted

March 23, 2021

Study Start

March 1, 2021

Primary Completion

September 1, 2022

Study Completion

November 1, 2022

Last Updated

November 2, 2022

Record last verified: 2022-11

Data Sharing

IPD Sharing
Will not share

Locations