Natural History Study of Individuals With Autism and Germline Heterozygous PTEN Mutations

NCT ID: NCT02461446

Last Updated: 2024-10-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

170 participants

Study Classification

OBSERVATIONAL

Study Start Date

2015-05-31

Study Completion Date

2026-12-31

Brief Summary

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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

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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.

Conditions

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PTEN ASD Autism Macrocephaly PTEN Hamartoma Tumor Syndrome

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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PTEN ASD

PTEN participants with Autism Spectrum Disorder group

No interventions assigned to this group

PTEN no ASD

PTEN participants without Autism Spectrum Disorder group

No interventions assigned to this group

Controls

Healthy control group

No interventions assigned to this group

Eligibility Criteria

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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.
* 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.
Minimum Eligible Age

18 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role collaborator

Office of Rare Diseases (ORD)

NIH

Sponsor Role collaborator

National Center for Advancing Translational Sciences (NCATS)

NIH

Sponsor Role collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role collaborator

Boston Children's Hospital

OTHER

Sponsor Role lead

Responsible Party

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Mustafa Sahin

Professor of Neurology, Harvard Medical School

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Antonio Hardan, MD

Role: STUDY_CHAIR

Stanford University

Locations

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University of California at Los Angeles

Los Angeles, California, United States

Site Status RECRUITING

Stanford University Medical Center

Stanford, California, United States

Site Status RECRUITING

Boston Children's Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status RECRUITING

Cleveland Clinic

Cleveland, Ohio, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Rajna Filip-Dhima, MS

Role: CONTACT

617-919-7068

Facility Contacts

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Julian Martinez, MD, PhD

Role: primary

Robin Libove

Role: primary

650-736-1235

Anna Cronin

Role: primary

617-919-3499

Adrienne Victory

Role: primary

513-636-8016

Beth Crouser

Role: primary

216-445-5850

References

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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.

Reference Type DERIVED
PMID: 33509259 (View on PubMed)

Other Identifiers

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1U54NS092090-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P00013150

Identifier Type: -

Identifier Source: org_study_id

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