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

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ClinicalTrials.gov Identifier: NCT02461446
Recruitment Status : Recruiting
First Posted : June 3, 2015
Last Update Posted : August 2, 2021
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Office of Rare Diseases (ORD)
National Center for Advancing Translational Science (NCATS)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Mustafa Sahin, Boston Children's Hospital

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.

Condition or disease
PTEN ASD Autism Macrocephaly PTEN Hamartoma Tumor Syndrome

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.

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Study Type : Observational
Estimated Enrollment : 170 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Natural History Study of Individuals With Autism and Germline Heterozygous PTEN Mutations
Study Start Date : May 2015
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : December 2025

Resource links provided by the National Library of Medicine


Group/Cohort
PTEN ASD
PTEN participants with Autism Spectrum Disorder group
PTEN no ASD
PTEN participants without Autism Spectrum Disorder group
Controls
Healthy control group



Primary Outcome Measures :
  1. Change in verbal abilities at 12 months [ Time Frame: 12 months ]
    Verbal and non-verbal ability will be evaluated using Stanford Binet -5 or Mullen Scales of Early Learning (MSEL) at 12 months

  2. Change in communication ability at 12 months [ Time Frame: 12 months ]
    Communication ability will be evaluated using composite score of the Peabody Picture Vocabulary Test (PPVT-4).

  3. Change in communication ability at 12 months [ Time Frame: 12 months ]
    Communication ability will be evaluated using composite score of the Expressive Vocabulary Test (EVT-2) at 12 months.

  4. Change in verbal abilities at 24 months [ Time Frame: 24 months ]
    Verbal and non-verbal ability will be evaluated using Stanford Binet 5 or Mullen Scales of Early Learning (MSEL) at 24 months

  5. Change in visual perception at 12 months [ Time Frame: 12 months ]
    Visual perception will be measured using the Beery Developmental Test of Visuomotor Integration (VMI) at 12 months

  6. Change in working memory at 12 months [ Time Frame: 12 months ]
    Working memory will be evaluated using the Stanford Binet 5 at 12 months

  7. Change in processing speed at 12 months [ Time Frame: 12 months ]
    Processing Speed will be measured using the Processing Speed Index from the Weschler Intelligence Scales at 12 months

  8. Change in working memory at 24 months [ Time Frame: 24 months ]
    Working memory will be evaluated using the Stanford Binet 5 at 24 months

  9. Change in processing speed at 24 months [ Time Frame: 24 months ]
    Processing Speed will be measured using the Processing Speed Index from the Weschler Intelligence Scales at 24 months

  10. Change in visual perception at 24 months [ Time Frame: 24 months ]
    Visual perception will be measured using the Beery Developmental Test of Visuomotor Integration (VMI) at 24 months

  11. Change in communication ability at 24 months [ Time Frame: 24 months ]
    Communication ability will be evaluated using composite score of the Peabody Picture Vocabulary Test (PPVT-4) at 24 months

  12. Change in communication ability at 24 months [ Time Frame: 24 months ]
    Communication ability will be evaluated using composite score of the Expressive Vocabulary Test (EVT-2) at 24 months.


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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Months and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
170 patients will be enrolled for this study, over the age of 18 month old.
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02461446


Contacts
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Contact: Rajna Filip-Dhima, MS 617-919-7068 Rajna.Filip-Dhima@childrens.harvard.edu

Locations
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United States, California
University of California at Los Angeles Recruiting
Los Angeles, California, United States, 90095
Contact: Irma Gutierrez    310-794-5065    IrmaGutierrez@mednet.ucla.edu   
Principal Investigator: Julian Martinez, MD, PhD         
Stanford University Medical Center Recruiting
Stanford, California, United States, 94305
Contact: Robin Libove    650-736-1235    rlibove@stanford.edu   
Principal Investigator: Antonio Hardan, MD         
United States, Massachusetts
Boston Children's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Emine Arcasoy    617-919-7624    Emine.Arcasoy@childrens.harvard.edu   
Principal Investigator: Mustafa Sahin, MD, PhD         
United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Molly Griffith    513-636-9669    Molly.Griffith@cchmc.org   
Principal Investigator: Darcy Krueger, MD, PhD         
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Beth Crouser    216-636-5535    crouseb@ccf.org   
Principal Investigator: Charis Eng, MD, PhD         
Sponsors and Collaborators
Boston Children's Hospital
National Institutes of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Office of Rare Diseases (ORD)
National Center for Advancing Translational Science (NCATS)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
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Study Chair: Charis Eng, MD, PhD The Cleveland Clinic
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Mustafa Sahin, Assistant in NeurologyAssociate Professor of Neurology, Harvard Medical School, Boston Children's Hospital
ClinicalTrials.gov Identifier: NCT02461446    
Other Study ID Numbers: P00013150
1U54NS092090-01 ( U.S. NIH Grant/Contract )
First Posted: June 3, 2015    Key Record Dates
Last Update Posted: August 2, 2021
Last Verified: July 2021
Keywords provided by Mustafa Sahin, Boston Children's Hospital:
germline heterozygous PTEN mutations
MRI
10q23.3
ASD
Autism
Macrocephaly
PTEN Hamartoma Tumor Syndrome
PTEN
EEG
Additional relevant MeSH terms:
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Hamartoma
Neoplasms
Hamartoma Syndrome, Multiple
Megalencephaly
Autistic Disorder
Autism Spectrum Disorder
Child Development Disorders, Pervasive
Neurodevelopmental Disorders
Mental Disorders
Neoplasms, Multiple Primary
Neoplastic Syndromes, Hereditary
Genetic Diseases, Inborn
Craniofacial Abnormalities
Musculoskeletal Abnormalities
Musculoskeletal Diseases
Malformations of Cortical Development, Group I
Malformations of Cortical Development
Nervous System Malformations
Nervous System Diseases
Congenital Abnormalities