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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 : July 19, 2017
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)
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 (ages 3 to 21), 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. 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 5 visits (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 and neuropsychological assessments and a blood draw done for laboratory studies. Individuals who have a clinically indicated MRI will have their scan extended for 15 minutes as part of this study.


Study Type : Observational
Estimated Enrollment : 120 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 2019
Estimated Study Completion Date : December 2019

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
PTEN Macrocephaly
PTEN participants with Macrocephaly 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), Expressive Vocabulary Test (EVT-2), and the Children's Communication Checklist (CCC-2) at 12 months

  3. 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

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

  5. 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

  6. 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

  7. Change in motor functioning at 12 months [ Time Frame: 12 months ]
    Motor functioning will be evaluated using the Purdue Pegboard (Pegs) 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 motor functioning at 24 months [ Time Frame: 24 months ]
    Motor functioning will be evaluated using the Purdue Pegboard (Pegs) 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 Peabody Picture Vocabulary Test (PPVT-4), Expressive Vocabulary Test (EVT-2), and the Children's Communication Checklist (CCC-2) at 24 months


Biospecimen Retention:   Samples With DNA
Blood draw for future correlative studies in the PTEN Biorepository of the Developmental Synaptopathies Consortium.


Information from the National Library of Medicine

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Ages Eligible for Study:   3 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
120 patients will be enrolled for this study, ages 3 to 21.
Criteria

Inclusion Criteria:

  • Individuals ages 3 to 21 years old at the time of consent who have documentation of a clinical diagnosis of autism spectrum disorder diagnosis 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.
  • Youth ages 3-17 and adults age 18-21 who do not have an autism spectrum disorder or a PTEN mutation for inclusion in the control group.
  • Consent from parents or guardians or an adult with or suspected of having an autism spectrum disorder that does not require a legal guardian or an adult who is the healthy sibling of an individual with an autism spectrum disorder.
  • Youths who are able (some young or severely impaired participants may not be able to provide assent) will be asked to provide assent.
  • 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:

  • Clinically significant medical disease that would prohibit participation in the study procedures.
  • Individuals with contraindication to MRI will be excluded from the MRI portion of the study such as:

    1. Cardiac pacemaker.
    2. Intracranial aneurysm clips, metallic implants or external clips within 10 mm of the head.
    3. Implanted metallic devices such as pumps or neuro-stimulator devices.
    4. Metallic foreign material within the orbits.
    5. Pregnancy.
    6. Claustrophobia.
  • No history of significant brain lesions or pathology including:

    1. History of large vessel strokes, brain tumors or previous neurosurgery.

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

Locations
United States, California
University of California at Los Angeles Recruiting
Los Angeles, California, United States, 90095
Contact: Dzung Maria Nguyen    310-794-5065    DzungNguyen@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: Sarah Mischianti    617-919-3499    Sarah.Mischianti@childrens.harvard.edu   
Principal Investigator: Mustafa Sahin, MD, PhD         
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Eric Klingemier    216-448-6392    klingee@ccf.org   
Contact: Kaitlin Sesock    216-636-5535    sesockk@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)
Investigators
Study Chair: Charis Eng, MD, PhD The Cleveland Clinic

Responsible Party: Mustafa Sahin, Assistant in NeurologyAssociate Professor of Neurology, Harvard Medical School, Boston Children’s Hospital
ClinicalTrials.gov Identifier: NCT02461446     History of Changes
Other Study ID Numbers: P00013150
1U54NS092090-01 ( U.S. NIH Grant/Contract )
First Posted: June 3, 2015    Key Record Dates
Last Update Posted: July 19, 2017
Last Verified: July 2017

Keywords provided by Mustafa Sahin, Boston Children’s Hospital:
germline heterozygous PTEN mutations
MRI
10q23.3
ASD
Autism
Macrocephaly
PTEN Hamartoma Tumor Syndrome
PTEN

Additional relevant MeSH terms:
Child Development Disorders, Pervasive
Malformations of Cortical Development, Group I
Malformations of Cortical Development
Autistic Disorder
Hamartoma
Neoplasms
Hamartoma Syndrome, Multiple
Megalencephaly
Neurodevelopmental Disorders
Mental Disorders
Neoplasms, Multiple Primary
Neoplastic Syndromes, Hereditary
Genetic Diseases, Inborn
Craniofacial Abnormalities
Musculoskeletal Abnormalities
Musculoskeletal Diseases
Nervous System Malformations
Nervous System Diseases
Congenital Abnormalities