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CompletedNCT02991807Updated Feb 17, 2025Results posted

RAD001 and Neurocognition in PTEN Hamartoma Tumor Syndrome

A Phase 1/2 interventional study of RAD001 and Placebo in PTEN Gene Mutation and PTEN Hamartoma Tumor Syndrome, sponsored by Boston Children's Hospital. Completed at 3 sites in United States. Open to participants aged 5 Years to 45 Years. Per ClinicalTrials.gov, last updated 2025-02-17.

Sponsored by Boston Children's Hospital · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
46
Allocation
Randomized
Ages
5 Years to 45 Years
Sex
All
01

Study summary

Phosphatase and TENsin homolog (PTEN) gene germline mutations are associated with a spectrum of clinical manifestations characterized by neurocognitive deficits, intellectual disability, autism symptomatology, skin lesions, macrocephaly, hamartomatous overgrowth of tissues, and an increased risk of cancers. Investigators are conducting research to evaluate the potential safety and efficacy of RAD001 (everolimus) in this patient population, and the potential neurocognitive benefits from treatment with RAD001 or placebo for a six month period. The investigators hope this trial will lead to a better understanding of PTEN and to new forms of treatment that may benefit children and adults with PTEN in the future.

Read the detailed description

This is a signal seeking Phase I/II 6-month, randomized, double-blind placebo-controlled trial of everolimus in individuals, ages 5 to 45 years with a PTEN mutation, with safety and neurocognition as the primary endpoints.

Participant's or a legal guardian will need to sign an informed consent prior to enrollment in the study. To determine eligibility participants will undergo a series of screening tests and safety measures. If determined to be eligible for the blinded phase of the study, participants will be randomly assigned to take either the study drug or a placebo (pill with no medicine).

The blinded phase of the study involves about eight visits, five of which will occur at the study site, and three of which will be conducted over the phone. These visits will take place over a six month period. Study visits will vary in length. Baseline, three month and six month visits may last up to 8 hours, if optional measures are done, while all other visits will be less than 2 hours. The study visits include blood draws, general health exams, and neuropsychological assessments. The study will also include optional eye-tracking, EEG and auditory evoked potential (AEP) measures, and the collection of microbiome/mycobiome and biomarker blood sample. There is no fee to participate in this study. The study drug will be provided at no charge during the study.

After the 6 month treatment phase, individuals who were randomly assigned to take placebo will be offered inclusion in a 6 month open label phase where the study drug will be provided at no charge. The open label phase assessments will be similar to those done in the blinded phase, but patients/families will only need to return to the study site three times during this phase.

Participants will receive a developmental assessments report after completing the study. After all study data has been analyzed, patients and families will also be informed of the overall results. Treatment on this study may or may not improve an individual's learning skills (neurocognition) or behavior. We hope that future patients and families will benefit from what is learned by this study.

Specific Aims /Objectives Primary objective

-To evaluate the safety of everolimus compared with placebo in patients with PTEN mutations focusing on NCI CTCAE Grade 3 and 4 adverse events, serious adverse events, and Grade 3 and 4 laboratory toxicities.

Secondary objectives

-To evaluate the efficacy of everolimus on neurocognition and behavior in inividuals with PTEN mutations compared to placebo as measured by standardized, direct and indirect neurocognitive tools and behavioral measures.

02

Conditions studied

  • PTEN Gene Mutation
  • PTEN Hamartoma Tumor Syndrome

Keywords

  • PTEN
  • PTEN Gene Mutation
  • PTEN Hamartoma Tumor Syndrome
  • Autism
  • Intellectual Disability
  • Neurocognition
  • Afinitor
  • Everolimus
  • RAD001
03

In context

Hamartoma Syndrome, Multiple

21 studies on the registry are indexed under Hamartoma Syndrome, Multiple; 9 are open to participants now.

Browse Hamartoma Syndrome, Multiple studies →

Lead sponsor

Boston Children's Hospital is the lead sponsor of 607 studies on the registry; 148 are open to participants now.

Of its 33 completed or terminated interventional studies of FDA-regulated products, 19 (58%) have results posted.

Browse Boston Children's Hospital studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
5 Years to 45 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Double-Blind Inclusion Criteria

  1. Male and female outpatients between 5 and 45 years of age (inclusive);
  2. Pathogenic PTEN mutation confirmed by clinical genetic testing;
  3. Participant must be able to complete one of the following three standardized assessments: Conners' Continuous Performance Tasks (CPT-3-mean reaction time), Stanford Binet (SB-5; working memory), or the Purdue Pegboard Test;
  4. Performance below the age-adjusted population mean on at least one of the above standardized measure: attention (CPT-3, mean reaction time), working memory (SB5), or fine motor skills (Purdue Pegboard Test; either dominant hand, non-dominant hand, or both hands);

  5. Adequate bone marrow function as shown by:

    1. platelets ≥ 80,000/mm3
    2. absolute neutrophil count ≥ 1,000/mm3
    3. hemoglobin ≥ 9 g/dL

  6. Adequate liver function as shown by:

    1. Total serum bilirubin \< 1.5 x ULN
    2. AST and ALT levels \< 2.5 x ULN
    3. INR ≤ 2
  7. Adequate renal function: serum creatinine \< 1.5 x ULN,
  8. Signed informed consent obtained prior to any screening procedures;
  9. Individuals on psychotropic and anti-epileptic medications should maintain a stable dose for at least 2 months prior to the screening visit;
  10. Negative serum pregnancy test for females at screening and no plans to become pregnant or conceive a child while participating in the study. The effects of mTOR inhibitors on the developing fetus at the doses used in this study are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of the study. Estrogen-containing oral contraceptives are not recommended in women enrolled in this study. Abstinence or two effective non-estrogen or barrier methods of contraception (such as condoms + spermicidal foam) must be used;
  11. No anticipated changes in the frequency and intensity of existing interventions such as behavioral and developmental treatments, in home services, and speech therapy;
  12. No planned changes in school placement;
  13. For individuals under 18 or who are otherwise incapable, there must be an available caregiver who can reliably bring subject to clinic visits and provide trustworthy data
  14. Able to communicate fluently in English

Double-Blind Exclusion Criteria

  1. Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of Everolimus (including chemotherapy, radiation therapy, antibody based therapy, etc.);
  2. Known intolerance or hypersensitivity to Everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus);
  3. Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral Everolimus;
  4. Uncontrolled diabetes mellitus as defined by HbA1c >8% despite adequate therapy. Patients with a known history of impaired fasting glucose or diabetes mellitus (DM) may be included, however blood glucose and antidiabetic treatment must be monitored closely throughout the trial and adjusted as necessary;
  5. Patient with uncontrolled hyperlipidemia: fasting serum cholesterol > 300 mg/dL OR >7.75 mmol/L AND fasting triglycerides > 2.5 x ULN.
  6. Patients who have any severe and/or uncontrolled medical or psychiatric conditions (see section 4.6 for additional details)
  7. Chronic treatment with corticosteroids or other immunosuppressive agents. Topical or inhaled corticosteroids are allowed;
  8. Known history of or seropositivity for Hepatitis B, Hepatitis C, or HIV;
  9. Patients who have received live attenuated vaccines within 1 week of start of Everolimus and during the study. Patient should also avoid close contact with others who have received live attenuated vaccines. Examples of live attenuated vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella and TY21a typhoid vaccines;

  10. Patients who have a history of another primary malignancy, with the exceptions of:

    1. non-melanoma skin cancer,
    2. and carcinoma in situ of the cervix, uteri, or breast from which the patient has been disease free for ≥3 years;
  11. Planned changes to concomitant medications;
  12. Prior or concomitant therapy with known or possible anti-mTOR activity, including rapamycin (sirolimus);
  13. Concomitant therapy with strong inhibitor (e.g., cyclosporine and ketoconazole) or inducer of CYP3A;
  14. Active infection at time of enrollment;
  15. Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will not be able to complete the entire study;
  16. Patients who are currently part of or have participated in any clinical investigation with an investigational drug within 1 month prior to dosing;
  17. Pregnant or nursing (lactating) women;

  18. Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, must use highly effective methods of contraception during the study and 8 weeks after. Highly effective contraception methods include:

    a. A combination of any two of the following: i. Use of oral, injected or implanted hormonal non-estrogen containing methods of contraception or; ii. Placement of an intrauterine device (IUD) or intrauterine system (IUS); iii. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository; b. Total abstinence or; c. Male/female sterilization. Women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to randomization. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child-bearing potential.

  19. Male patients whose sexual partner(s) are WOCBP who are not willing to use adequate contraception, during the study and for 8 weeks after the end of treatment
  20. Major surgery, radiation therapy, or stereotactic radio-surgery within previous 4 weeks at time of screening
  21. Neurosurgery within prior 6 months at time of screening.

Open-Label Inclusion Criteria

  1. Patients who completed Double-Blind phase of the study and were assigned to the placebo treatment arm;
  2. Verbal consent (and assent, as appropriate) obtained prior to any open-label phase study procedures.
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
46 participants (actual)

Study arms

  • Experimental
    RAD001

    RAD001 is formulated as tablets of 5.0 mg or 2.5mg strength, blister-packed under aluminum foil in units of 10 tablets and dosed on a regular basis.

    Drug: RAD001

  • Placebo comparator
    Placebo

    Matching placebo will be provided as a matching tablet and will also be blister packed under aluminum foil in units of 10.

    Drug: Placebo

Interventions

  • DrugRAD001

    RAD001 is formulated as tablets of 5.0 mg strength, blister-packed under aluminum foil in units of 10 tablets and dosed on a regular basis. RAD001 tablets should be opened only at the time of administration as drug is both hygroscopic and light-sensitive. Patients will be instructed to take 4.5 mg/m2 of RAD001 orally with a glass of water at regular intervals at the same time (delete: each day) in the morning after a light, nonfat breakfast.

    Also known as: Everolimus, Afinitor

  • DrugPlacebo

    Matching placebo will be provided as a matching tablet and will also be blister packed under aluminum foil in units of 10. Matching placebo tablets should be opened only at the time of administration as drug is both hygroscopic and light-sensitive. Patients will be instructed to take 4.5 mg/m2 of the matching placebo orally with a glass of water at regular intervals at the same time (delete: each day) in the morning after a light, nonfat breakfast.

06

What researchers measure

Primary outcomes

  1. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Dropout

    The primary endpoint will be safety as measured by study drop-out rate due to side effects, comparing everolimus vs. placebo. We will also determine the frequency of adverse events by type and severity. This section displays participant dropout rate and for what reason.

    Time frame: Through study completion, an average of 6 months

  2. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants)

    The primary endpoint will be safety as measured by study drop-out rate due to side effects, comparing everolimus vs. placebo. We will also determine the frequency of adverse events by type and severity. this section displays the number of participants who experienced an AE and the description of such AEs, pertaining to: 1. Seriousness 2. Grade, 3. Relation to treatment 4. Recovery from AE 5. Category

    Time frame: Through study completion, an average of 6 months

Secondary outcomes

  1. Change at 6 Months in Composite Score

    Composite score was based on the following: Stanford-Binet Intelligence Scales, 5th Ed (SB-5) non-verbal and verbal working memory standard score; for the SB-5, the minimum score is 40 and the maximum score is 160, where the higher score represents a better outcome. Conners' Continuous Performance Test, 3rd Ed (CPT-3) hit reaction time standard score (reverse coded; standard score generated from T-score); for the CPT-3, the min score is 0 and the max score is 90, where the lower the T-score, the better the outcome. Purdue Pegboard Test (PPT) both hands standard score (generated from T-score); for the PPT, the min score is 20 and the max score is 190, where the higher the T-score, the better the outcome. For the composite score, the higher the score, the better the outcome. The composite score is on the SS metric (M=100, SD=15, min=20, max=180).

    Time frame: 6 months

  2. Change in Processing Speed at 6 Months, Conner's Continuous Performance Test (CPT)-3

    Processing speed will be evaluated using mean reaction time on the Conner's Continuous Performance Test (CPT)-3. This outcome evaluates the change from baseline to 6 months.

    Time frame: 6 months

  3. Change in Fine Motor Skills at 6 Months, Purdue Pegboard

    Fine motor skills will be evaluated using the Purdue Pegboard sub-tests average of both hands. This outcome evaluates the change from baseline to 6 months.

    Time frame: 6 months

  4. Change in Global Cognitive Ability at 6 Months, Stanford-Binet Intelligence Scales, Fifth Edition (SB-5) or Mullen Scales of Early Learning

    Change in global cognitive ability will be measured by Stanford-Binet 5 or Mullen; Full scale, verbal and nonverbal ability (IQ). This outcome evaluates the change from baseline to 6 months.

    Time frame: 6 months

  5. Change in Motor Functioning at 6 Months, Purdue Pegboard and Developmental Coordination Disorder Questionnaire (DCDQ)

    Motor functioning will be measured by the Purdue Pegboard (Pegs): Dominant and non-dominant hand combined standard scores and Developmental Coordination Disorder Questionnaire (DCDQ): Total score. This outcome evaluates the change from baseline to 6 months.

    Time frame: 6 months

  6. Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months

    1. Change in memory measured by Wide Range Assessment of Memory and Learning (WRAML-2) verbal learning core subtest, delayed recall, and recognition scaled scores over 6 months. 2. Change in executive functioning measured by Behavior Rating Inventory of Executive Function (BRIEF-2) global executive composite standard score over 6 months. 3. Change in autism symptoms measured by Social Responsiveness Scale (SRS-2) total standard score and Repetitive Behaviors Scale (RBS-R) total subscale score over 6 months. 4. Change in adaptive behaviors measured by Vineland Adaptive Behavior Scales (VABS-III) adaptive behavior composite standard score over 6 months. 5. Change in other behaviors measured by Child Behavior Checklist (CBCL) total problems standard score and Short Sensory Profile (SSP) total score over 6 months.

    Time frame: 6 months

07

Results

Posted Feb 17, 2025
Limitations and caveats
1\) Small sample size, as recruitment is difficult for rare neurogenetic disorders. 2) A subset of participants was unable to complete all assessments, largely due to the COVID-19 pandemic. Amidst COVID-19 pandemic, participants completed instruments remotely when possible. CPT-3 hit reaction time had a sample size n\<10 at the month 6 timepoint, while the other measures had reasonable sample sizes. 3) Enrollment numbers were insufficient to power subgroup analysis, such as participants with ASD.

Participant flow

Participant flow — Overall Study
MilestoneRAD001Placebo
Started2422
Completed2120
Not completed32
Withdrew: Withdrawal by subject21
Withdrew: Physician decision01
Withdrew: Investigator decision at baseline given safety concerns related to drug administration compliance10

Outcome measures

PrimaryIncidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Dropout

The primary endpoint will be safety as measured by study drop-out rate due to side effects, comparing everolimus vs. placebo. We will also determine the frequency of adverse events by type and severity. This section displays participant dropout rate and for what reason.

Time frame:
Through study completion, an average of 6 months
Reported as:
Count of participants · Participants
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Dropout
ParticipantsRAD001PlaceboTotal
Dropout (Total)325
Dropout due to participant/parent request213
Dropout due to investigator request011
Dropout due to other requests101
PrimaryIncidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants)

The primary endpoint will be safety as measured by study drop-out rate due to side effects, comparing everolimus vs. placebo. We will also determine the frequency of adverse events by type and severity. this section displays the number of participants who experienced an AE and the description of such AEs, pertaining to: 1. Seriousness 2. Grade, 3. Relation to treatment 4. Recovery from AE 5. Category

Time frame:
Through study completion, an average of 6 months
Reported as:
Number · percentage of participants
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants)
percentage of participantsRAD001PlaceboTotal
Any AE (%)87.559.173.9
Non-serious AEs (%)87.559.173.9
Serious AEs (%)12.506.5
Grade 1 (%)7545.560.9
Grade 2 (%)5018.234.8
Grade 3 (%)16.708.7
Grade 4 (%)000
Grade 5 (%)000
Definitely not related to treatment (%)20.827.323.9
Probably not related to treatment (%)37.518.228.3
Possibly or probably related to treatment (%)70.831.852.2
Definitely related to treatment (%)12.506.5
Patients not recovered/not resolved from AEs (%)04.52.2
Patients recovered/resolved with sequelae form AEs (%)4.202.2
Patients recovered/resolved without sequelae fro AEs (%)83.359.171.7
Patients recovering/resolving from AEs (%)8.334.3
SecondaryChange at 6 Months in Composite Score

Composite score was based on the following: Stanford-Binet Intelligence Scales, 5th Ed (SB-5) non-verbal and verbal working memory standard score; for the SB-5, the minimum score is 40 and the maximum score is 160, where the higher score represents a better outcome. Conners' Continuous Performance Test, 3rd Ed (CPT-3) hit reaction time standard score (reverse coded; standard score generated from T-score); for the CPT-3, the min score is 0 and the max score is 90, where the lower the T-score, the better the outcome. Purdue Pegboard Test (PPT) both hands standard score (generated from T-score); for the PPT, the min score is 20 and the max score is 190, where the higher the T-score, the better the outcome. For the composite score, the higher the score, the better the outcome. The composite score is on the SS metric (M=100, SD=15, min=20, max=180).

Time frame:
6 months
Reported as:
Mean · score on a scale
Change at 6 Months in Composite Score
score on a scaleRAD001 - BaselinePlacebo - BaselineRAD001 - 6 MonthsPlacebo - 6 Months
Change at 6 Months in Composite Score80.34 ± 15.2375.14 ± 18.3081.60 ± 17.1778.47 ± 21.96
SecondaryChange in Processing Speed at 6 Months, Conner's Continuous Performance Test (CPT)-3

Processing speed will be evaluated using mean reaction time on the Conner's Continuous Performance Test (CPT)-3. This outcome evaluates the change from baseline to 6 months.

Time frame:
6 months
Reported as:
Mean · score on a scale
Change in Processing Speed at 6 Months, Conner's Continuous Performance Test (CPT)-3
score on a scaleRAD001 - BaselinePlacebo - BaselineRAD001 - 6 MonthsPlacebo - 6 Months
Change in Processing Speed at 6 Months, Conner's Continuous Performance Test (CPT)-387.78 ± 2086.30 ± 16.1689.26 ± 22.3590.15 ± 15.46
SecondaryChange in Fine Motor Skills at 6 Months, Purdue Pegboard

Fine motor skills will be evaluated using the Purdue Pegboard sub-tests average of both hands. This outcome evaluates the change from baseline to 6 months.

Time frame:
6 months
Reported as:
Mean · score on a scale
Change in Fine Motor Skills at 6 Months, Purdue Pegboard
score on a scaleRAD001 - BaselinePlacebo - BaselineRAD001 - 6 MonthsPlacebo - 6 Months
Change in Fine Motor Skills at 6 Months, Purdue Pegboard62.83 ± 20.5255.92 ± 23.5667.12 ± 20.0861.49 ± 33.37
SecondaryChange in Global Cognitive Ability at 6 Months, Stanford-Binet Intelligence Scales, Fifth Edition (SB-5) or Mullen Scales of Early Learning

Change in global cognitive ability will be measured by Stanford-Binet 5 or Mullen; Full scale, verbal and nonverbal ability (IQ). This outcome evaluates the change from baseline to 6 months.

Time frame:
6 months
Reported as:
Mean · score on a scale
Change in Global Cognitive Ability at 6 Months, Stanford-Binet Intelligence Scales, Fifth Edition (SB-5) or Mullen Scales of Early Learning
score on a scaleRAD001 - BaselinePlacebo - BaselineRAD001 - 6 MonthsPlacebo - 6 Months
Full Scale (FSIQ)77.83 ± 19.8575.19 ± 22.9079.39 ± 17.3074.79 ± 25.79
Verbal (VIQ)78.79 ± 19.7376.05 ± 23.6778.46 ± 18.0578.71 ± 27.07
Nonverbal (NVIQ)78.96 ± 19.0375.91 ± 22.7082.31 ± 16.2573.15 ± 22.87
SecondaryChange in Motor Functioning at 6 Months, Purdue Pegboard and Developmental Coordination Disorder Questionnaire (DCDQ)

Motor functioning will be measured by the Purdue Pegboard (Pegs): Dominant and non-dominant hand combined standard scores and Developmental Coordination Disorder Questionnaire (DCDQ): Total score. This outcome evaluates the change from baseline to 6 months.

Time frame:
6 months
Reported as:
Mean · score on a scale
Change in Motor Functioning at 6 Months, Purdue Pegboard and Developmental Coordination Disorder Questionnaire (DCDQ)
score on a scaleRAD001 - BaselinePlacebo - BaselineRAD001 - 6 MonthsPlacebo - 6 Months
Purdue Pegboard (right hand)66.92 ± 22.8358.64 ± 27.8371.68 ± 30.1861.47 ± 35.48
Purdue Pegboard (left hand)66.46 ± 23.0261.82 ± 20.9175.92 ± 24.7660.26 ± 29.30
Purdue Pegboard (dominant hand)67.92 ± 21.9258.63 ± 27.9175.60 ± 24.7859.25 ± 32.48
Purdue Pegboard (non-dominant hand)69.37 ± 21.9261.89 ± 27.9175.58 ± 24.7862.36 ± 32.48
DCDQ Total Score37.51 ± 12.3836.29 ± 14.2040.01 ± 10.6237.64 ± 16.37
SecondaryChange in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months

1. Change in memory measured by Wide Range Assessment of Memory and Learning (WRAML-2) verbal learning core subtest, delayed recall, and recognition scaled scores over 6 months. 2. Change in executive functioning measured by Behavior Rating Inventory of Executive Function (BRIEF-2) global executive composite standard score over 6 months. 3. Change in autism symptoms measured by Social Responsiveness Scale (SRS-2) total standard score and Repetitive Behaviors Scale (RBS-R) total subscale score over 6 months. 4. Change in adaptive behaviors measured by Vineland Adaptive Behavior Scales (VABS-III) adaptive behavior composite standard score over 6 months. 5. Change in other behaviors measured by Child Behavior Checklist (CBCL) total problems standard score and Short Sensory Profile (SSP) total score over 6 months.

Time frame:
6 months
Reported as:
Mean · score on a scale
Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months
score on a scaleRAD001 - BaselinePlacebo - BaselineRAD001 - 6 MonthsPlacebo - 6 Months
WRAML-2 verbal learning core subtest scaled score6.11 ± 2.656.90 ± 3.367.47 ± 3.937.22 ± 3.76
WRAML-2 verbal learning delayed recall scaled score6.73 ± 2.026.57 ± 3.408.13 ± 2.987.72 ± 2.99
WRAML-2 verbal learning recognition scaled score5.94 ± 3.495.97 ± 3.146.74 ± 3.966.42 ± 4.22
BRIEF-2 global executive composite standard score77.68 ± 19.7771.18 ± 19.3582.61 ± 17.4374.24 ± 16.97
SRS-2 total standard score73.12 ± 18.2367.52 ± 19.6078.91 ± 17.7566.90 ± 19.36
RBS-R total subscale score16.44 ± 16.8323.35 ± 19.9814.42 ± 5.8619.96 ± 16.06
VABS-III adaptive behavior composite standard score76.96 ± 14.4474.41 ± 18.2181.56 ± 10.4574.71 ± 15.75
CBCL total problems standard score85.90 ± 13.8280.54 ± 18.0790.10 ± 13.2881.53 ± 14.80
SSP total score137.46 ± 21.68128.25 ± 26.05143.08 ± 16.54126.52 ± 28.09

Adverse events

Collected over 6 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
RAD0010/24 (0%)3/24 (12.5%)21/24 (87.5%)
Placebo0/22 (0%)0/22 (0%)13/22 (59.1%)
Most frequent serious events
Most frequent serious events
EventRAD001Placebo
Suicidal ideationPsychiatric disorders1/240/22
Renal lesionsRenal and urinary disorders1/240/22
Enterovirus infectionInfections and infestations1/240/22
Most frequent other events
Showing 10 of 56
Most frequent other events
EventRAD001Placebo
Mucositis OralGastrointestinal disorders7/241/22
StomatitisSkin and subcutaneous tissue disorders4/240/22
StomatitisGeneral disorders3/240/22
CoughRespiratory, thoracic and mediastinal disorders1/242/22
Runny NoseRespiratory, thoracic and mediastinal disorders0/242/22
Middle Ear InflammationEar and labyrinth disorders2/240/22
DiarrheaGastrointestinal disorders2/241/22
Oral PainGastrointestinal disorders2/240/22
Rash AcneiformSkin and subcutaneous tissue disorders2/240/22
Rash Maculo-PapularSkin and subcutaneous tissue disorders2/240/22

Baseline characteristics

Age, Continuous
Age, Continuous(years)RAD001PlaceboTotal
Mean16.5 ± 11.314.7 ± 10.915.6 ± 11.0
Sex: Female, Male
Sex: Female, Male(Participants)RAD001PlaceboTotal
Female11718
Male131528
Race (NIH/OMB)
Race (NIH/OMB)(Participants)RAD001PlaceboTotal
American Indian or Alaska Native000
Asian000
Native Hawaiian or Other Pacific Islander000
Black or African American112
White201838
More than one race112
Unknown or Not Reported224
Autism spectrum disorder (n)
Autism spectrum disorder (n)(participants)RAD001PlaceboTotal
Number6814
Autism spectrum disorder (%)
Autism spectrum disorder (%)(percentage of participants)RAD001PlaceboTotal
Number2536.330.4
Stanford-Binet Intelligence Scales, Fifth Edition (SB-5): Mean full scale IQ (FSIQ)
Stanford-Binet Intelligence Scales, Fifth Edition (SB-5): Mean full scale IQ (FSIQ)(scores on a scale)RAD001PlaceboTotal
Mean77.8 ± 20.375.2 ± 23.576.6 ± 21.6
08

Study locations

3 sites
  • Stanford University
    Palo Alto, California 94305, United States
  • Boston Children's Hospital
    Boston, Massachusetts 02115, United States
  • Cleveland Clinic
    Cleveland, Ohio 44104, United States
09

References and documents

Publications

  • Srivastava S, Jo B, Zhang B, Frazier T, Gallagher AS, Peck F, Levin AR, Mondal S, Li Z, Filip-Dhima R, Geisel G, Dies KA, Diplock A, Eng C, Hanna R, Sahin M, Hardan A; Developmental Synaptopathies Consortium. A randomized controlled trial of everolimus for neurocognitive symptoms in PTEN hamartoma tumor syndrome. Hum Mol Genet. 2022 Oct 10;31(20):3393-3404. doi: 10.1093/hmg/ddac111. PubMed 35594551 ↗

Study documents

  • Protocol and statistical analysis plan · Mar 13, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Data will be shared with the National Database of Autism Research (NDAR)

10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Ran from Jun 2017 to primary completion in Feb 2021, 44 months.

Results were first posted in Feb 2025, 3 years 11 months after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered
Dec 2, 2016
First posted
Dec 14, 2016
StartActual
Jun 12, 2017
Primary completionActual
Feb 18, 2021
CompletionActual
Dec 22, 2021
Results first posted
Feb 17, 2025
Last update
Feb 17, 2025
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Feb 17, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02991807
Lead sponsor
Boston Children's Hospital
Collaborators
National Institutes of Health (NIH), National Institute of Neurological Disorders and Stroke (NINDS), Office of Rare Diseases (ORD), National Center for Advancing Translational Sciences (NCATS), Novartis Pharmaceuticals, PTEN Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Responsible party
Mustafa Sahin (Director, Translational Neuroscience Center/ Professor of Neurology, Harvard Medical School, Boston Children's Hospital) — Principal investigator
First posted
Dec 14, 2016
Start date
Jun 12, 2017
Primary completion
Feb 18, 2021
Completion
Dec 22, 2021
Results posted
Feb 17, 2025
Last update
Feb 17, 2025

Study contacts

Mustafa Sahin, MD, PhD
principal investigator · Boston Children's Hospital

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Feb 2025. You cannot join it, but the record below documents what was studied.

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