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

NCT07218575 | Not Yet Recruiting Phase 2 FDA Drug

• 2 other identifiers: IRB-P00049577109110
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Cowden's Disease; Cowden's Syndrome; Lhermitte-Duclos Disease; Cerebellum Dysplastic Gangliocytoma; Bannayan Zonana Syndrome; Myhre Riley Smith Syndrome; Riley Smith Syndrome; PTEN Hamartoma Tumor Syndrome; Bannayan Riley Ruvalcaba Syndrome

Keywords

PTEN mutation; Autism

Outcome Measures

Primary Outcomes (1)

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

  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)

  Baseline, month 1, month 2, month 3, month 4, month 5, month 6

Secondary Outcomes (3)

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

  Month 1, month 2, month 3, month 4, month 5, month 6

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

  Baseline, month 1, month 2, month 3, month 4, month 5, month 6

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

  Baseline, month 1, month 2, month 3, month 4, month 5, month 6

Other Outcomes (21)

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

  Baseline, month 1, month 2, month 3, month 4, month 5, month 6

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

  Baseline, month 6

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

  Baseline, month 3, month 6

Study Arms (2)

Everolimus

EXPERIMENTAL

Everolimus, oral capsules once daily for 12 months; initiated at 2.5mg/day and then increased every 2-3 weeks until a therapeutic blood level is achieved

Drug: Everolimus blinded oral capsules

Placebo

PLACEBO COMPARATOR

Placebo matched to everolimus oral capsules once daily for 6 months, Initiated at 1 tablet per day and then increased every 2-3 weeks to maintain blind. Then Everolimus, oral capsules once daily for 6 months

Drug: Placebo

Interventions

Everolimus blinded oral capsules DRUG

Oral capsules given once daily for the first 6 months

Also known as: Afinitor, Zortress

Everolimus

Placebo DRUG

Oral capsules given once daily for the first 6 months

Placebo

Eligibility Criteria

• Age: 5 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Boston Children's Hospital: lead

MeSH Terms

Conditions

Hamartoma Syndrome, Multiple; Autistic Disorder

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Hamartoma; Neoplasms; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Autism Spectrum Disorder; Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Neurology, Harvard Medical School

Study Record Dates

• First Submitted: October 15, 2025
• First Posted: October 20, 2025
• Study Start: April 1, 2026
• Primary Completion (Estimated): April 1, 2030
• Study Completion (Estimated): April 1, 2030
• Last Updated: October 20, 2025

Record last verified: 2025-10