Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome

Autism Spectrum Disorder Clinical Trial

Official title:

Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02461420
• Other study ID #: P00013300
• Secondary ID: 1U54NS092090
• Status: Recruiting
• Start date: May 2015
• Est. completion date: December 2026

Study information

• Verified date: November 2023
• Source: Boston Children's Hospital
• Contact: Rajna Filip-Dhima, MS
• Phone: 617-919-7068
• Email: Rajna.Filip-Dhima[@]childrens.harvard.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to comprehensively characterize PMS using standardized medical, cognitive, and behavioral measures and to track the natural history of the syndrome using repeated longitudinal assessments. In addition, this study will be aiming to identify biomarkers using neuroimaging, including diffusion tensor imaging and identify genetic factors which contribute to diverse phenotypes in patients with PMS.

Description:

Phelan-McDermid syndrome (PMS) or 22q13 Deletion syndrome, caused by a loss of one copy of the SHANK3 gene, is characterized by global developmental delay/intellectual disability, motor skills deficits, delayed or absent speech, and autism spectrum disorder. The goal of this study is to understand more about the PMS phenotype and the biological pathways associated with ID and ASD in the disorder, and to establish the foundation for future clinical trials in PMS and in other ID/ASD-associated disorders that share signaling pathways with PMS. Individuals with PMS will be asked to participate in this study if they are 18 months or older with pathogenic deletions or mutations of the SHANK3 gene at time of enrollment, as well as healthy controls. Both males and females will be asked to participate. Additionally, to be eligible for study participation, individuals' primary communicative language must be English. Parents and unaffected siblings may also be asked to consent to have blood drawn for analysis. The study involves 3 on site visits over 2 years. Study visits involve a physical exam, medical history questions, blood work and neuropsychological assessments. A subset of participants between the ages of 2 and 11 years old will take part in the EEG portion of the study. Individuals who have a clinically indicated MRI will have an option to provide routine clinical scans for analysis.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 190
• Est. completion date: December 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Months and older

Eligibility

Inclusion Criteria:

• Individuals older than 18 months of age with pathogenic deletions or mutations of the SHANK3 gene
• English speaking individuals

Exclusion Criteria:

• Has taken an investigational drug as part of another research study, within 30 days prior to study enrollment
• For subjects involved in imaging biomarker assessment: contraindications to 3T MRI scanning, such as metal implants/non-compatible medical devices or medical conditions, including vagus nerve stimulator
• For subjects involved in EEG/ ERP biomarker assessment: contraindications to EEG/ERP, such as uncooperative or destructive behaviors preventing lead placement or capture by ERP/VEP equipment. Under age 2 or over age 11 at the time of enrollment.
• Unwilling or unable to comply with study procedures and assessments

Related Conditions & MeSH terms

• Autism Spectrum Disorder
• Chromosome Deletion
• Chromosome Disorders
• Intellectual Disability
• Phelan-McDermid Syndrome
• Syndrome

Locations

Country	Name	City	State
United States	National Institutes of Health	Bethesda	Maryland
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Rush University Medical Center	Chicago	Illinois
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Stanford University	Stanford	California

Sponsors (7)

Lead Sponsor	Collaborator
Boston Children's Hospital	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Center for Advancing Translational Sciences (NCATS), National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Office of Rare Diseases (ORD), Phelan-McDermid Syndrome Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in global cognitive ability at 12 months	Using Mullen Scales for Early Learning or Stanford Binet-5 to measure global cognitive ability	12 months
Primary	Change in adaptive behavior at 12 months	Using Vineland Adaptive Behavior Scales to measure adaptive behavior	12 months
Primary	Change in language abilities at 12 months	Using composite of Mullen Subscales, Vineland Subscales and Macarthur Bates Communication Developmental Inventory to measure language	12 months
Primary	Change in motor functioning at 12 months	Using composite of Mullen Subscales and Vineland Subscales to measure motor functioning	12 months
Primary	Change in autism symptoms at 12 months	Using composite of Autism Diagnostic Observation Schedule and Repetitive Behavior Scales-Revised to measure autism	12 months
Primary	Change in global cognitive ability at 24 months	Using Mullen Scales for Early Learning or Stanford Binet-5 to measure global cognitive ability	24 months
Primary	Change in adaptive behavior at 24 months	Using Vineland Adaptive Behavior Scales to measure adaptive behavior	24 months
Primary	Change is language abilities at 24 months	Using composite of Mullen Subscales, Vineland Subscales and Macarthur Bates Communication Developmental Inventory to measure language	24 months
Primary	Change in motor functioning at 24 months	Using composite of Mullen Subscales and Vineland Subscales to measure motor functioning	24 months
Primary	Change in autism symptoms at 24 months	Using composite of Autism Diagnostic Observation Schedule and Repetitive Behavior Scales-Revised to measure autism	24 months