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NCT Number: NCT07218575

Double-Blind Trial of Everolimus for Improving Social Abilities in PTEN Germline Mutations

The goal of this study is to examine the safety and treatment effects of everolimus in adults and children with PTEN Hamartoma Tumor Syndrome (PHTS) who experience social difficulties. The study will measure if everolimus can safely improve social abilities and functioning in this study population.

PTEN Hamartoma Tumor Syndrome (PHTS) is a genetic condition that results from alteration (germline variant) to the PTEN gene. It is associated with a wide range of symptoms and characteristics, which vary from individual to individual. These include symptoms such as harmatomas (non-cancerous lesions), an increased risk of certain types of cancer, having a larger than average head, and abnormalities in blood vessels. Some people also have neurobehavioral problems including social difficulties. It is estimated approximately 25% (1 in 4) of people with PHTS meet the criteria for an autism diagnosis.

The study lasts for one year. In the first 6 months half of participants will receive everolimus as a once daily oral tablet, and half will receive placebo tablets. For the second 6 months all participants will receive everolimus. Visits to the study clinic are required at the start, month 3, month 6, month 9 and month 12, with phone calls or virtual visits in between. Assessments include questionnaires, blood tests and urine tests, physical and neurological exams, and vital signs.

Everolimus is an existing FDA approved medication used to treat other conditions, including a genetic condition called tuberous sclerosis complex which has some similarities to PHTS, and several types of cancer.

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Key information

Conditions

Cowden's Disease Autism Spectrum Disorder Autistic Disorder Bannayan Riley Ruvalcaba Syndrome Bannayan Zonana Syndrome Cerebellum Dysplastic Gangliocytoma Child Development Disorders, Pervasive Congenital, Hereditary, and Neonatal Diseases and Abnormalities Cowden's Syndrome Genetic Diseases, Inborn Hamartoma Hamartoma Syndrome, Multiple Lhermitte-Duclos Disease Mental Disorders Myhre Riley Smith Syndrome Neoplasms Neoplasms, Multiple Primary Neoplastic Syndromes, Hereditary Neurodevelopmental Disorders PTEN Hamartoma Tumor Syndrome Riley Smith Syndrome

Age range

5 year–45 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

Stanford University, Stanford, California, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Diagnosis of PTEN Harmartoma Tumor Syndrom (PHTS), confirmed by genetic testing (the testing may be done as part of study screening)
  • Experiences at least moderate levels of social difficulties, based on SRS T score > 60 (measured during screening Have at least a moderate impairment in social abilities, based on SRS score during study screening
  • Fluent in English
  • Females of child-bearing potential must have no plans to become pregnant and be using contraception during the study (if sexually active).
  • Availability of parent, care-giver, partner or other suitable individual who can provide observation reports and provide transportation to attend clinic visits
  • Adequate liver, kidney and bone-marrow function (checked during screening)
  • Medically stable
  • No plans to change school, behavioral therapies, home services or speech therapy during the study period
  • Ability to swallow medicine in pill form

Exclusion criteria

  • Ongoing or planned treatment with any medication with known or possible ant-mTOR activity (e.g. sirolimus), or strong inducers or inhibitors of CYP3A, CYP2D6, P450 or PgP (e.g. cyclosporine, ketoconazole, erythromycin, rifampin, phenytoin, phenobarbital) or ACE inhibitors
  • Chronic treatment with systemic corticosteroids or other immunosuppressive treatments (topical or inhaled corticosteroids are allowed).
  • Major surgery or any anti-cancer therapies (including radiotherapy) within 4 weeks of enrollment
  • Neurosurgery within 6 months of enrollment
  • Uncontrolled diabetes defined as HbA1c >8% despite treatment
  • Uncontrolled hyperlipidemia (defined as fasting serum cholesterol > 300 mg/dL OR >7.75 mmol/L AND fasting triglycerides > 2.5 x ULN, assessed during screening)
  • History of Hepatitis B, Hepatitis C or HIV
  • Participation in a clinical trial in the 60 days prior to study entry
  • Known intolerance or hypersensitivity to everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus)
  • Patients who have a history of another primary malignancy, with the exceptions of non-melanoma skin cancer, and carcinoma in situ of the cervix, uteri, or breast from with the patient has been disease free for > 3 years

Treatment and study plan

Everolimus blinded oral capsules

Drug

Oral capsules given once daily for the first 6 months

Other names: Afinitor, Zortress

Placebo

Drug

Oral capsules given once daily for the first 6 months

Primary outcomes

  1. Change from baseline in severity of social skill deficits based on Social Responsiveness Scale (SRS) total score over 6 months.

    Time frame: Baseline, month 1, month 2, month 3, month 4, month 5, month 6

    The SRS is a well-validated, reliable, and widely used measure for identifying and measuring impairments in social processing and associated behaviors. It is completed by an observer who knows the participant well (e.g. parent, care-giver, partner)

Secondary outcomes

  1. Change in overall global clinical assessment of social abilities based on the Clinical Global Impressions (CGI) Improvement scale over 6 months

    Time frame: Month 1, month 2, month 3, month 4, month 5, month 6

    The Clinical Global Impressions (CGI) Improvement rating scale assesses improvement or worsening of symptoms since the start of treatment.

  2. Change from baseline in social skills and processes based on the Stanford Social Dimensions Scale (SSDS)

    Time frame: Baseline, month 1, month 2, month 3, month 4, month 5, month 6

    The Stanford Social Dimensions Scale (SSDS) has been developed to measure an individual's social skills and processes, and is completed by an observer who knows the participant well (e.g. parent, care-giver, partner)

  3. Change from baseline in the Social Communications Sub-scale of the Social Responsiveness Scale (SRS)

    Time frame: Baseline, month 1, month 2, month 3, month 4, month 5, month 6

    The Social Responsiveness Scale (SRS) Social Communication Subscale is part of the SRS questionnaire which is focused on assessment of an individual's ability to communicate and interact with others. It is completed by an observer who knows the participant well (e.g. parent, care-giver, partner)

Other outcomes

  1. Change from baseline in Clinical Global Impression (CGI) Severity Scale

    Time frame: Baseline, month 1, month 2, month 3, month 4, month 5, month 6

    The Clinical Global Impression (CGI) Severity Scale is a rating scale designed to assess severity of symptoms.

  2. Change from baseline in Brief Observation of Social Communication Change (BOSCC)

    Time frame: Baseline, month 6

    The Brief Observation of Social Communication Change (BOSCC) is an instrument that assesses changes in social communication and other autism related social communication behaviors.

  3. Change from baseline in Neurobehavioral Evaluation Tool (NET) - Social Communication and Interaction Subscale

    Time frame: Baseline, month 3, month 6

    The Neurobehavioral Evaluation Tool (NET) is designed to incorporate webcam collected performance measures and informant reported survey responses focusing on autism and other neurobehavioral symptoms. We will evaluate the Social Communication and Interaction Subscale.

  4. Change from baseline in Reading the Mind in the Eyes Test (RMET)

    Time frame: Baseline, month 3, month 6

    The Reading the Mind in the Eyes Test (RMET) is used to evaluate theory of mind, the ability to understand another individual's thoughts.

  5. Change from baseline in Purdue Pegboard Test

    Time frame: Baseline, month 6

    The Purdue Pegboard Test evaluates motor coordination and dexterity.

  6. Change from baseline in Neurobehavioral Evaluation Tool (NET) - Motor subscale

    Time frame: Baseline, month 3, month 6

    The Neurobehavioral Evaluation Tool (NET) is designed to incorporate webcam collected performance measures and informant reported survey responses focusing on autism and other neurobehavioral symptoms. We will evaluate the Motor subscale of this tool.

  7. Change from baseline in Dimensional Assessment of Restricted/Repetitive Behaviors (DARB)

    Time frame: Baseline, month 3, month 6

    The Dimensional Assessment of Repetitive Behaviors (DARB) assess various restricted and repetitive behaviors and interests

  8. Change from baseline in Neurobehavioral Evaluation Tool (NET) - Restricted, Repetitive Behavior subscale

    Time frame: Baseline, month 3, month 6

    The Neurobehavioral Evaluation Tool (NET) is designed to incorporate webcam collected performance measures and informant reported survey responses focusing on autism and other neurobehavioral symptoms. We will evaluate the Restricted, Repetitive Behavior subscale.

  9. Change from baseline in Adult/Child Behavior Checklist (ABCL/CBCL)

    Time frame: Baseline, month 3, month 6

    The Adult/Child Behavior Checklist (ABCL/CBCL) instrument evaluates behavioral and emotional problems in children, adolescents, and adults.

  10. Change from baseline in Neurobehavioral Evaluation Tool (NET) - Disruptive Behaviors subscale.

    Time frame: Baseline, month 3, month 6

    The Neurobehavioral Evaluation Tool is designed to incorporate webcam collected performance measures and informant reported survey responses focusing on autism and other neurobehavioral symptoms. We will evaluate the Disruptive Behaviors subscale.

  11. Change from baseline in Sensory Profile Questionnaire - Short Form

    Time frame: Baseline, month 3, month 6

    The Sensory Profile Questionnaire - Short Form is an assessment of sensory processing features.

  12. Change from baseline in Vineland Adaptive Behavior Scales, 3rd Edition (VABS-3)

    Time frame: Baseline, month 6

    The Vineland Adaptive Behavior Scales, 3rd Edition (VABS-3) characterizes self help skills across a number of different domains.

  13. Change from baseline in Neurobehavioral Evaluation Tool (NET) - Daily Living Skills and Quality of Life Subscales

    Time frame: Baseline, month 3, month 6

    The Neurobehavioral Evaluation Tool (NET) is designed to incorporate webcam collected performance measures and informant reported survey responses focusing on autism and other neurobehavioral symptoms. We will evaluate the Daily Living Skills and Quality of Life subscales.

  14. Change from baseline in Stanford-Binet 5th Edition (SB-5)

    Time frame: Baseline, month 6

    The Stanford-Binet 5th edition (SB-5) is used to characterize various aspects of cognition in children and adults.

  15. Change from baseline in Mullen Scales of Early Learning (MSEL)

    Time frame: Baseline, month 6

    The Mullen Scales of Early Learning (MSEL) is a developmental assessment tool evaluating language, motor, and other abilities.

  16. Change from baseline in Behavior Rating Inventory of Executive Function (BRIEF)

    Time frame: Baseline, month 3, month 6

    The Behavior Rating Inventory of Executive Function (BRIEF) is a tool that evaluates executive functioning in children, adolescents, and adults.

  17. Change from baseline in Neurobehavioral Evaluation Tool (NET) - Executive Functioning subscale

    Time frame: Baseline, month 3, month 6

    The Neurobehavioral Evaluation Tool (NET) is designed to incorporate webcam collected performance measures and informant reported survey responses focusing on autism and other neurobehavioral symptoms. We will evaluate the Executive Functioning subscale.

  18. Change from baseline in the Wide Range Assessment of Memory and Learning-2 (WRAML-2)

    Time frame: Baseline, month 6

    This instrument evaluates memory and cognitive abilities.

  19. Change from baseline in resting state and task-based EEG biomarkers

    Time frame: Baseline, month 6

    Resting state and task-based EEG will also be collected during in person visits to the study sites to examine target engagement of everolimus in the brain.

  20. Change from baseline in eye tracking biomarkers

    Time frame: Baseline, month 3, month 6

    We will assess target engagement in the brain with eye tracking biomarkers

  21. Changes in total/phosphorylated PTEN-associated protein levels

    Time frame: Screening visit, month 6

    We will examine if PTEN-associated molecules (mTOR, MAPK, PI3K/AKT) are affected by everolimus, and assess changes with treatment in total/phosphorylated protein levels from peripheral blood mononuclear cells.

Sponsors and collaborators

Lead sponsor

Boston Children's Hospital

Other

Registry information

Official study title

A Randomized, Placebo Controlled Double-Blind Trial of Everolimus for Improving Social Abilities in PTEN Germline Mutations

Important dates

Study start
2026
Primary completion
2030
Study completion
2030
First posted
Oct 20, 2025
Registry last updated
Jun 4, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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