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

Conditions

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

Eligibility Criteria

Sex

ALL

Age

5 Years - 45 Years

Healthy Volunteers

Not accepted

Interventions

• Everolimus blinded oral capsules — DRUG
  Oral capsules given once daily for the first 6 months
• Placebo — DRUG
  Oral capsules given once daily for the first 6 months

Study Details

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.

Key Dates

Start date

Sep 1, 2026

Status verified

Oct 2025

Primary completion

Sep 30, 2030

Completion

Sep 30, 2030

Study Design

Enrollment

60 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Everolimus
  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
• Placebo Comparator: Placebo
  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

Primary Outcome Measure

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 ]

Locations (3)

Find similar trials in Stanford, CA

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