Cowden's DiseasePhase 2/3NCT07218575
Double-Blind Trial of Everolimus for Improving Social Abilities in PTEN Germline Mutations
A Phase 2/3 study testing Everolimus blinded oral capsules in people with Cowden's Disease and Cowden's Syndrome, run by Boston Children's Hospital at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 5 to 45 years
- Conditions the study is for
- Cowden's Disease, Cowden's Syndrome, Lhermitte-Duclos Disease
- What is being tested?
- Everolimus blinded oral capsules
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 3 sitesUnited States
- Study dates
- 1 Sep 2026to Sep 2030
- Phase
- Phase 2/3
- 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 5 to 45 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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)
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- 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
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States3 sites
Boston Children's Hospital
Boston, Massachusetts, 02115
Sydney Klau, 6179197623, sydney.klau@childrens.harvard.edu
Siddharth Srivastava, MD
Cleveland Clinic
Cleveland, Ohio, 44195
Beth Crouser, 216-445-5850, crouseb2@ccf.org
Xiangling Wang, MD
Stanford University
Stanford, California, 94305
Seigo Ninomiya, (650) 736-1235, PTENConnect@stanford.edu
Antonio Y. Hardan, MD
About this study
Official title: A Randomized, Placebo Controlled 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.
Read more
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
- Being tested
- Everolimus blinded oral capsules, Placebo
- Keywords
- PTEN mutation, Autism
- Medical subject headings
- Hamartoma Syndrome, Multiple, Autistic Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Everolimus blinded oral capsulesDrug
Also called Afinitor, Zortress
Oral capsules given once daily for the first 6 months
PlaceboDrug
Oral capsules given once daily for the first 6 months
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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
The Clinical Global Impressions (CGI) Improvement rating scale assesses improvement or worsening of symptoms since the start of treatment.
Measured: 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)
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)
Measured: 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)
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)
Measured: Baseline, month 1, month 2, month 3, month 4, month 5, month 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2025
- Study start1 Sep 2026 (estimated)
- Primary completionSep 2030 (estimated)
- Study completionSep 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cowden's DiseaseStudies 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
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Boston Children's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Siddharth Srivastava, Boston Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07218575
- Sponsor's protocol ID
- IRB-P00049577
- Other IDs
- 109110
- Status last verified
- Oct 2025
- First submitted
- 15 Oct 2025
- Last updated
- 4 Jun 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Placebo Controlled Double-Blind Trial of Everolimus for Improving Social Abilities in PTEN Germline Mutations
- ClinicalTrials.gov ID
- NCT07218575
- Acronym / sponsor ID
- IRB-P00049577
- Conditions
- Cowden's Disease, Cowden's Syndrome, Lhermitte-Duclos Disease, Cerebellum Dysplastic Gangliocytoma, Bannayan Zonana Syndrome, Myhre Riley Smith Syndrome
- Keywords
- PTEN mutation, Autism
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Boston Children's HospitalUniversity, hospital or other
- Study start
- 1 Sep 2026 (estimated)
- Primary completion
- Sep 2030 (estimated)
- Study completion
- Sep 2030 (estimated)
- First posted
- 20 Oct 2025 (actual)
- 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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Everolimus | Experimental | Drug: Everolimus blinded oral capsulesEverolimus, 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 | Placebo comparator | Drug: PlaceboPlacebo 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 |
Who may qualify
- Ages
- 5 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Everolimus blinded oral capsulesAlso: Afinitor, ZortressOral capsules given once daily for the first 6 months | Drug | Everolimus |
| PlaceboOral capsules given once daily for the first 6 months | Drug | Placebo |
Primary outcome
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)
3 secondary outcomes
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
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
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
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 4 Jun 2026.
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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.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Everolimus blinded oral capsules in people with Cowden's Disease and Cowden's Syndrome, run by Boston Children's Hospital at 3 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 9 inclusion and 10 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: opening soon, as of the sponsor's last update on 4 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Jun 2026.