Development and Validation of an Online Neurobehavioral Evaluation Tool for PTEN Patients

Development and Validation of an Online Neurobehavioral Evaluation Tool for PTEN Hamartoma Tumor Syndrome (PHTS)

The purpose of this study is to develop a survey completed by parents, caregivers, or other informants that evaluates several important domains of functioning relevant to individuals with neurodevelopmental disorders, including autism spectrum disorder and people with genetic syndromes. Participation in this research will include assisting the research team in the development of the survey measures.

Study Overview

• Status: Active, not recruiting
• Conditions: PTEN Hamartoma Tumor Syndrome
• Intervention / Treatment: Diagnostic test: NET

Detailed Description

With greater understanding of the biology of PTEN Hamartoma Tumor Syndrome (PHTS), including patients with and without neurodevelopmental disorder (NDD) phenotypes, there is potential to develop novel personalized therapeutics. Given the recent observation that many PHTS patients with and without NDD have significant neurobehavioral manifestations, it will be crucial to broadly track a range of neurobehavioral domains as part of future trials. Unfortunately, there are few well-validated measures that would be appropriate for the full range of presentations in the PHTS population. Further, as a rare genetic syndrome, PHTS patients are geographically distributed making frequent data collection during research very difficult. Thus, the overarching aim of this proposal is to develop and validate an online neurobehavioral evaluation tool (NET) with caregiver-report survey scales and patient-completed webcam-collected performance measures that captures key neurobehavioral information. In partnership with patients, caregivers, and scientist-clinician experts, the study will develop, pilot test, and validate NET survey and performance measures. Specifically, at least 240 caregiver-patient pairs will be recruited (patient ages 4-24) from PHTS without NDD, PHTS with NDD, and controls (sibling and unrelated healthy controls). NET data will be collected at baseline, 1-month, and 4-month follow-up. Aim 1 will focus on the development and validation of brief, psychometrically-sound NET survey scales. Aim 2 will conduct group comparisons on NET measures. Aim 3 will use longitudinal data to evaluate short-term stability of NET survey scales and describe neurobehavioral change within and across study groups. The project will also explore the feasibility of performance measure collection, provide initial psychometric evaluation, and conduct a group comparison of performance measures. If the project aims are achieved, and future validation supports research and clinical use, the NET will be an efficient, reliable, valid, co-normed, multi-modal instrument, that, by virtue of online (at-home) administration, will decrease patient and family burden and increase the temporal resolution and power of future longitudinal studies and clinical trials.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

Study Locations

• United Kingdom
  • Southampton
    • Hampton, Southampton, United Kingdom, S016 6YD
      • University Hospital South Hampton
• United States
  • Ohio
    • University Heights, Ohio, United States, 44118
      • John Carroll Univeristy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 45 years (Child, Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Community sample

Description

Inclusion Criteria:

• Has a PTEN Hamartoma Tumor Syndrome diagnosis with or without a neurodevelopment disorder
• Access to a tablet (10+ inch screen), laptop, or desktop computer
• Access to reliable internet
• Able to attend to short videos (30 plus seconds)
• Able to hear audio from a computer device
• Able to see without corrective lenses

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
PTEN - with NDD; Patients diagnosed with PTEN Hamartoma Tumor Syndrome and a neurodevelopmental disorder including but not limited to autism spectrum disorder, attention-deficit disorder / attention-deficit hyperactivity disorder, speech language disorder(s), intellectual disability, global developmental delay, oppositional defiant disorder, and / or motor or developmental disorders.	Diagnostic test: NET; Online survey measuring a variety of developmental domains including anxiety, motor, daily living skills, challenging behaviors, social communication, restrictive and repetitive behaviors, ADHD, executive functioning, mood, quality of life, and sleep
PTEN - without NDD; Patients diagnosed with PTEN Hamartoma Tumor Syndrome	Diagnostic test: NET; Online survey measuring a variety of developmental domains including anxiety, motor, daily living skills, challenging behaviors, social communication, restrictive and repetitive behaviors, ADHD, executive functioning, mood, quality of life, and sleep
Sibling Controls; Siblings related to patients with diagnosis of PTEN Hamartoma Tumor Syndrome	Diagnostic test: NET; Online survey measuring a variety of developmental domains including anxiety, motor, daily living skills, challenging behaviors, social communication, restrictive and repetitive behaviors, ADHD, executive functioning, mood, quality of life, and sleep
Unrelated Controls; Unrelated participants with no known genetic or neurodevelopmental disorder	Diagnostic test: NET; Online survey measuring a variety of developmental domains including anxiety, motor, daily living skills, challenging behaviors, social communication, restrictive and repetitive behaviors, ADHD, executive functioning, mood, quality of life, and sleep

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Social Communication Interaction	Develop survey questions and scales related content areas for Social Communication Interactions. Social communication refers to the emergence of verbal and nonverbal skills, social interaction, and social cognition	Baseline
Social Communication Interaction	Develop survey questions and scales related content areas for Social Communication Interactions. Social communication refers to the emergence of verbal and nonverbal skills, social interaction, and social cognition	One month follow up
Social Communication Interaction	Develop survey questions and scales related content areas for Social Communication Interactions. Social communication refers to the emergence of verbal and nonverbal skills, social interaction, and social cognition	Four month follow up
Daily Living Skills	Develop questions and survey scales related to content areas of activities of daily living. Activities of daily living are activities related to personal care. They include bathing or showering, dressing, getting in and out of bed or a chair, walking, using the toilet, and eating.	Baseline
Daily Living Skills	Develop questions and survey scales related to content areas of activities of daily living. Activities of daily living are activities related to personal care. They include bathing or showering, dressing, getting in and out of bed or a chair, walking, using the toilet, and eating.	One month follow up
Daily Living Skills	Develop questions and survey scales related to content areas of activities of daily living. Activities of daily living are activities related to personal care. They include bathing or showering, dressing, getting in and out of bed or a chair, walking, using the toilet, and eating.	Four months later

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Restrictive and Repetitive Behaviors	Develop survey and rating scales related to content areas for restrictive and repetitive behaviors. Restricted and repetitive behaviors and interests are among the three core symptoms of autism. They include repetitive movements with objects, repeated body movements such as rocking and hand-flapping, ritualistic behavior, sensory sensitivities and circumscribed interests	Baseline
Restrictive and Repetitive Behaviors	Develop survey and rating scales related to content areas for restrictive and repetitive behaviors. Restricted and repetitive behaviors and interests are among the three core symptoms of autism. They include repetitive movements with objects, repeated body movements such as rocking and hand-flapping, ritualistic behavior, sensory sensitivities and circumscribed interests	One month follow up
Restrictive and Repetitive Behaviors	Develop survey and rating scales related to content areas for restrictive and repetitive behaviors. Restricted and repetitive behaviors and interests are among the three core symptoms of autism. They include repetitive movements with objects, repeated body movements such as rocking and hand-flapping, ritualistic behavior, sensory sensitivities and circumscribed interests	Four month follow up
Anxiety	Develop survey questions and scales related to content areas for anxiety. Anxiety is what we feel when we are worried, tense or afraid - particularly about things that are about to happen, or which we think could happen in the future	Baseline
Anxiety	Develop survey questions and scales related to content areas for anxiety. Anxiety is what we feel when we are worried, tense or afraid - particularly about things that are about to happen, or which we think could happen in the future	One month follow up
Anxiety	Develop survey questions and scales related to content areas for anxiety. Anxiety is what we feel when we are worried, tense or afraid - particularly about things that are about to happen, or which we think could happen in the future	Four month follow up
Motor Skills	Develop survey questions and scales related to content areas for motor skills.A motor skill is a function that involves specific movements of the body's muscles to perform a certain task. These tasks could include walking, running, or riding a bike. In order to perform this skill, the body's nervous system, muscles, and brain have	Baseline
Motor Skills	Develop survey questions and scales related to content areas for motor skills.A motor skill is a function that involves specific movements of the body's muscles to perform a certain task. These tasks could include walking, running, or riding a bike. In order to perform this skill, the body's nervous system, muscles, and brain have	One month follow up
Motor Skills	Develop survey questions and scales related to content areas for motor skills.A motor skill is a function that involves specific movements of the body's muscles to perform a certain task. These tasks could include walking, running, or riding a bike. In order to perform this skill, the body's nervous system, muscles, and brain have	Four month follow up
Challenging Behaviors	Develop survey questions and rating scales related to content areas for challenging behaviors.A person's behaviour can be defined as "challenging" if it puts them or those around them (such as their carer) at risk, or leads to a poorer quality of life. It can also impact their ability to join in everyday activities. Challenging behaviour can include: aggression. self-harm.	Baseline
Challenging Behaviors	Develop survey questions and rating scales related to content areas for challenging behaviors.A person's behaviour can be defined as "challenging" if it puts them or those around them (such as their carer) at risk, or leads to a poorer quality of life. It can also impact their ability to join in everyday activities. Challenging behaviour can include: aggression. self-harm.	One month follow up
Challenging Behaviors	Develop survey questions and rating scales related to content areas for challenging behaviors.A person's behaviour can be defined as "challenging" if it puts them or those around them (such as their carer) at risk, or leads to a poorer quality of life. It can also impact their ability to join in everyday activities. Challenging behaviour can include: aggression. self-harm.	Four month follow up
ADHD	Develop survey questions and rating scales related to content areas for ADHD. Refers to the ongoing pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning or development.	Baseline
ADHD	Develop survey questions and rating scales related to content areas for ADHD. Refers to the ongoing pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning or development.	One month follow up
ADHD	Develop survey questions and rating scales related to content areas for ADHD. Refers to the ongoing pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning or development.	Four month follow up
Executive Functioning	Develop survey questions and rating scales related to content areas for executive functioning. Executive functioning and self-regulation skills are the mental processes that enable us to plan, focus attention, remember instructions, and juggle multiple tasks successfully.	Baseline
Executive Functioning	Develop survey questions and rating scales related to content areas for executive functioning. Executive functioning and self-regulation skills are the mental processes that enable us to plan, focus attention, remember instructions, and juggle multiple tasks successfully.	One month follow up
Executive Functioning	Develop survey questions and rating scales related to content areas for executive functioning. Executive functioning and self-regulation skills are the mental processes that enable us to plan, focus attention, remember instructions, and juggle multiple tasks successfully.	Four month follow up
Mood	Develop survey questions and rating scales related to content areas for mood. Focusing on particular feelings or a state of mind.	Baseline
Mood	Develop survey questions and rating scales related to content areas for mood. Focusing on particular feelings or a state of mind.	One month follow up
Mood	Develop survey questions and rating scales related to content areas for mood. Focusing on particular feelings or a state of mind.	Four month follow up
Quality of Life	Develop survey questions and rating scales related to content areas for quality of life including family, financial, etc.	Baseline
Quality of Life	Develop survey questions and rating scales related to content areas for quality of life including family, financial, etc.	One month follow up
Quality of Life	Develop survey questions and rating scales related to content areas for quality of life including family, financial, etc.	Four month follow up
Sleep	Develop survey questions and rating scales related to content areas for sleep patterns and behaviors.	Baseline
Sleep	Develop survey questions and rating scales related to content areas for sleep patterns and behaviors.	One month follow up
Sleep	Develop survey questions and rating scales related to content areas for sleep patterns and behaviors.	Four month follow up

Collaborators and Investigators

• Sponsor: John Carroll University
• Collaborators: University Hospital Southampton NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2021
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: December 16, 2022
• First Submitted That Met QC Criteria: January 3, 2023
• First Posted (Actual): January 4, 2023

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Autism; PTEN; Neurobehavioral; Neurodevelopmental disorders; PHTS; Online Assessment
• Additional Relevant MeSH Terms: Pathologic Processes; Disease; Genetic Diseases, Inborn; Neoplastic Syndromes, Hereditary; Neoplasms, Multiple Primary; Neoplasms; Syndrome; Hamartoma Syndrome, Multiple; Hamartoma
• Other Study ID Numbers: 2021-013; JCU-20-001 (Other Grant/Funding Number: PTEN Research Foundation)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Plan to upload deidentified data to Open Science Framework
• IPD Sharing Time Frame: Within one year of study completion
• IPD Sharing Supporting Information Type: CSR

Drug and device information, study documents

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