PTENNCT02461446
Natural History Study of Individuals With Autism and Germline Heterozygous PTEN Mutations
An observational study of PTEN and ASD, run by Boston Children's Hospital at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 months and olderHealthy volunteers can take part
- How many people
- 180 participants
- Where
- 5 sitesUnited States
- Study dates
- May 2015to Dec 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 months and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: 170 patients will be enrolled for this study, over the age of 18 month old.
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Boston Children's Hospital
Boston, Massachusetts, 02115
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Cleveland Clinic
Cleveland, Ohio, 44195
University of California at Los Angeles
Los Angeles, California, 90095
Stanford University Medical Center
Stanford, California, 94305
About this study
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.
Read the 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.
- 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
- Medical subject headings
- Autistic Disorder, Megalencephaly, Hamartoma Syndrome, Multiple
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| PTEN ASD | PTEN participants with Autism Spectrum Disorder group | |
| PTEN no ASD | PTEN participants without Autism Spectrum Disorder group | |
| Controls | Healthy control group |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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).
Measured: 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.
Measured: 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
Measured: 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
Measured: 12 months
Change in working memory at 12 months
Working memory will be evaluated using the Stanford Binet 5 at 12 months
Measured: 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
Measured: 12 months
Change in working memory at 24 months
Working memory will be evaluated using the Stanford Binet 5 at 24 months
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2015 (estimated)
- Study startMay 2015
- Primary completionDec 2025
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PTENStudies of the same condition, open and under way.
- More trials run by Boston Children's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 180 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Neurological Disorders and Stroke (NINDS), Office of Rare Diseases (ORD), National Center for Advancing Translational Sciences (NCATS), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Principal investigator, Mustafa Sahin, Boston Children's Hospital
- Investigators
- Antonio Hardan, MD, Study chair, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02461446
- Sponsor's protocol ID
- P00013150
- Other IDs
- 1U54NS092090-01
- Status last verified
- Aug 2026
- First submitted
- 11 May 2015
- Last updated
- 6 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 33509259
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Natural History Study of Individuals With Autism and Germline Heterozygous PTEN Mutations
- ClinicalTrials.gov ID
- NCT02461446
- Acronym / sponsor ID
- P00013150
- 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
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 180 participants (actual)
- Lead sponsor
- Boston Children's HospitalUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Neurological Disorders and Stroke (NINDS), Office of Rare Diseases (ORD), National Center for Advancing Translational Sciences (NCATS), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- May 2015
- Primary completion
- Dec 2025 (actual)
- Study completion
- Dec 2026 (estimated)
- First posted
- 3 Jun 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| PTEN ASD | – | –PTEN participants with Autism Spectrum Disorder group |
| PTEN no ASD | – | –PTEN participants without Autism Spectrum Disorder group |
| Controls | – | –Healthy control group |
Who may qualify
- Ages
- 18 months and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- 170 patients will be enrolled for this study, over the age of 18 month old.
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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
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).
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.
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
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
Change in working memory at 12 months
Time frame: 12 months
Working memory will be evaluated using the Stanford Binet 5 at 12 months
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
Change in working memory at 24 months
Time frame: 24 months
Working memory will be evaluated using the Stanford Binet 5 at 24 months
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
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
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
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2026.
- Derived from this study: PubMed 33509259Frazier 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.
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Testing the Addition of an Anti-cancer Drug, Copanlisib, to the Usual Immunotherapy (Nivolumab With or Without Ipilimumab) in Patients With Advanced Solid Cancers That Have Changes in the Following Genes: PIK3CA and PTEN
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Antonio Hardan, MD study chair
Stanford University
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of PTEN and ASD, run by Boston Children's Hospital at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 6 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in verbal abilities at 12 months (time frame: 12 months). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02461446, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2026.