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
Conditions
Keywords
PTEN mutation, Autism
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.
Interventions
DRUGEverolimus blinded oral capsules
Oral capsules given once daily for the first 6 months
DRUGPlacebo
Oral capsules given once daily for the first 6 months
Sponsors
Boston Children's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
5 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of PTEN Harmartoma Tumor Syndrom (PHTS), confirmed by genetic testing (the testing may be done as part of study screening) 2. 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 3. Fluent in English 4. Females of child-bearing potential must have no plans to become pregnant and be using contraception during the study (if sexually active). 5. Availability of parent, care-giver, partner or other suitable individual who can provide observation reports and provide transportation to attend clinic visits 6. Adequate liver, kidney and bone-marrow function (checked during screening) 7. Medically stable 8. No plans to change school, behavioral therapies, home services or speech therapy during the study period 9. Ability to swallow medicine in pill form
Exclusion criteria
1. 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 2. Chronic treatment with systemic corticosteroids or other immunosuppressive treatments (topical or inhaled corticosteroids are allowed). 3. Major surgery or any anti-cancer therapies (including radiotherapy) within 4 weeks of enrollment 4. Neurosurgery within 6 months of enrollment 5. Uncontrolled diabetes defined as HbA1c \>8% despite treatment 6. 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) 7. History of Hepatitis B, Hepatitis C or HIV 8. Participation in a clinical trial in the 60 days prior to study entry 9. Known intolerance or hypersensitivity to everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus) 10. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in severity of social skill deficits based on Social Responsiveness Scale (SRS) total score over 6 months. | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | The Clinical Global Impressions (CGI) Improvement rating scale assesses improvement or worsening of symptoms since the start of treatment. |
| 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 | 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) |
| 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 | 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) |
Countries
United States
Outcome results
None listed