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

NCT02461446 | Recruiting DMC

• 2 other identifiers: P000131501U54NS092090-01
• Study Type: observational
• Target: 170
• Locations: 1 country
• Sites: 5

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.

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

Outcome Measures

Primary Outcomes (12)

• Change in verbal abilities at 12 months

  Verbal and non-verbal ability will be evaluated using Stanford Binet -5 or Mullen Scales of Early Learning (MSEL) at 12 months

  12 months

• Change in communication ability at 12 months

  Communication ability will be evaluated using composite score of the Peabody Picture Vocabulary Test (PPVT-4).

  12 months

• Change in communication ability at 12 months

  Communication ability will be evaluated using composite score of the Expressive Vocabulary Test (EVT-2) at 12 months.

  12 months

• Change in verbal abilities at 24 months

  Verbal and non-verbal ability will be evaluated using Stanford Binet 5 or Mullen Scales of Early Learning (MSEL) at 24 months

  24 months

• Change in visual perception at 12 months

  Visual perception will be measured using the Beery Developmental Test of Visuomotor Integration (VMI) at 12 months

  12 months

• Change in working memory at 12 months

  Working memory will be evaluated using the Stanford Binet 5 at 12 months

  12 months

• Change in processing speed at 12 months

  Processing Speed will be measured using the Processing Speed Index from the Weschler Intelligence Scales at 12 months

  12 months

• Change in working memory at 24 months

  Working memory will be evaluated using the Stanford Binet 5 at 24 months

  24 months

• Change in processing speed at 24 months

  Processing Speed will be measured using the Processing Speed Index from the Weschler Intelligence Scales at 24 months

  24 months

• Change in visual perception at 24 months

  Visual perception will be measured using the Beery Developmental Test of Visuomotor Integration (VMI) at 24 months

  24 months

• Change in communication ability at 24 months

  Communication ability will be evaluated using composite score of the Peabody Picture Vocabulary Test (PPVT-4) at 24 months

  24 months

• Change in communication ability at 24 months

  Communication ability will be evaluated using composite score of the Expressive Vocabulary Test (EVT-2) at 24 months.

  24 months

Study Arms (3)

PTEN ASD

PTEN participants with Autism Spectrum Disorder group

PTEN no ASD

PTEN participants without Autism Spectrum Disorder group

Controls

Healthy control group

Eligibility Criteria

• Age: 18 Months+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

170 patients will be enrolled for this study, over the age of 18 month old.

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Boston Children's Hospital: lead
• National Institutes of Health (NIH): collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• Office of Rare Diseases (ORD): collaborator
• National Center for Advancing Translational Sciences (NCATS): collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (5)

University of California at Los Angeles

Los Angeles, California, 90095, United States

RECRUITING

Stanford University Medical Center

Stanford, California, 94305, United States

RECRUITING

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

Related Publications (1)

• 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.

  PMID: 33509259 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Blood draw for future correlative studies in the PTEN Biorepository of the Developmental Synaptopathies Consortium. 170 subjects; 100 existing subjects, 70 newly enrolled participants; 50 controls

MeSH Terms

Conditions

Autistic Disorder; Megalencephaly; Hamartoma Syndrome, Multiple

Condition Hierarchy (Ancestors)

Autism Spectrum Disorder; Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Musculoskeletal Diseases; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Nervous System Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hamartoma; Neoplasms; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn

Study Officials

• Antonio Hardan, MD

  Stanford University

  STUDY CHAIR

Central Study Contacts

Rajna Filip-Dhima, MS

CONTACT

617-919-7068; Rajna.Filip-Dhima@childrens.harvard.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurology, Harvard Medical School

Study Record Dates

• First Submitted: May 11, 2015
• First Posted: June 3, 2015
• Study Start: May 1, 2015
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: October 26, 2024

Record last verified: 2024-10

Locations

US (5)