Clinical trial NCT02461446: Natural History Study of Individuals With Autism and Germline Heterozygous PTEN Mutations
Official title: Natural History Study of Individuals With Autism and Germline Heterozygous PTEN Mutations
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: PTEN
ASD
Autism
Macrocephaly
PTEN Hamartoma Tumor Syndrome
Keywords: germline heterozygous PTEN mutations
MRI
10q23.3
ASD
Autism
Macrocephaly
PTEN Hamartoma Tumor Syndrome
PTEN
EEG
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute of Neurological Disorders and Stroke (NINDS)
name: Office of Rare Diseases (ORD)
name: National Center for Advancing Translational Sciences (NCATS)
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2015-06-03
Enrollment: 170
Sex: ALL
Minimum age (years): 18
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 170 patients will be enrolled for this study, over the age of 18 month old.

Brief summary: The purpose of this study is to determine cross-sectional and longitudinal medical, behavioral, and cognitive differences between PTEN ASD and other groups, as well as to identify cognitive, neural systems, and molecular biomarkers specific to PTEN ASD. In addition, this study will be creating and maintaining a biorepository and linked phenotypic database for PTEN ASD.

Detailed description: Autism spectrum disorders (ASD) are a set of neurodevelopmental disorders characterized by social communication/interaction impairments and restricted/repetitive behaviors. ASD associated with germline heterozygous PTEN mutations (PTEN ASD) is a genetically defined sub-group that, may be one of the more prevalent genetic disorders contributing to ASD (0.5-2%). The purpose of this research study is to carefully track the phenotypic and molecular characteristics of PTEN ASD and identify biomarkers for intervention studies.

Individuals with PTEN ASD, with macrocephalic ASD without a PTEN mutation (macro-ASD), healthy controls, and individuals with PTEN mutations without ASD (PTEN no-ASD) will be asked to participate in this study if they are 18 months and older. Both males and females will be asked to participate. Additionally, to be eligible for study participation, individuals' primary communicative language must be English.

The study involves 3 on site visits over the course of two years. Study visits will vary in length from about 4 hours to 6 hours. Study visits involve a physical exam, medical history questions, neuropsychological assessments, and a blood draw done for laboratory studies. 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.

Eligibility criteria: Inclusion Criteria

* Individuals above the age of 18 months old at the time of consent who have documentation of a clinical diagnosis of autism spectrum disorder and/or a verified PTEN mutation from a medical or mental health professional for inclusion in the PTEN ASD, PTEN no-ASD or ASD macrocephaly groups.
* Macrocephaly (head circumference greater than or equal to 98th percentile) for inclusion in the ASD macrocephaly group.
* For youths, consent from parents or legal guardian. For adults, consent from self or legal guardian.
* Youths who are able (some young or severely impaired participants may not be able to provide assent) will be asked to provide assent as per IRB guidelines.
* Families with multiple children who meet the above inclusion criteria will be permitted to have as many children participate as they wish. A separate consent form will be filled out for each child enrolled in the study.
* Primary communicative language must be English

Exclusion Criteria

* Unwilling or unable to comply with study procedures and assessments
* Clinically significant medical disease that would prohibit participation in the study procedures.
* For subjects ELIGIBLE FOR OPTIONAL 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 ELIGIBLE FOR 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 11 at the time of enrollment.

Primary outcomes:
measure: Change in verbal abilities at 12 months
timeFrame: 12 months
measure: Change in communication ability at 12 months
timeFrame: 12 months
measure: Change in communication ability at 12 months
timeFrame: 12 months
measure: Change in verbal abilities at 24 months
timeFrame: 24 months
measure: Change in visual perception at 12 months
timeFrame: 12 months
measure: Change in working memory at 12 months
timeFrame: 12 months
measure: Change in processing speed at 12 months
timeFrame: 12 months
measure: Change in working memory at 24 months
timeFrame: 24 months
measure: Change in processing speed at 24 months
timeFrame: 24 months
measure: Change in visual perception at 24 months
timeFrame: 24 months
measure: Change in communication ability at 24 months
timeFrame: 24 months
measure: Change in communication ability at 24 months
timeFrame: 24 months
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California at Los Angeles
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
Study officials:
affiliation: Stanford University
name: Antonio Hardan, MD
role: STUDY_CHAIR
References:
citation: Frazier TW, Jaini R, Busch RM, Wolf M, Sadler T, Klaas P, Hardan AY, Martinez-Agosto JA, Sahin M, Eng C; Developmental Synaptopathies Consortium. Cross-level analysis of molecular and neurobehavioral function in a prospective series of patients with germline heterozygous PTEN mutations with and without autism. Mol Autism. 2021 Jan 28;12(1):5. doi: 10.1186/s13229-020-00406-6.