Brief Title
Efficacy of RAD001/Everolimus in Autism and NeuroPsychological Deficits in Children With Tuberous Sclerosis Complex
Official Title
Efficacy of RAD001/Everolimus in Autism and NeuroPsychological Deficits in Children With Tuberous Sclerosis Complex
Brief Summary
Tuberous sclerosis complex (TSC) is a genetic disease that leads to mental retardation in
over 50% of patients, and to learning problems, behavioral problems, autism and epilepsy in
up to 90% of patients. The underlying deficit of TSC, loss of inhibition of the mammalian
target of rapamycin (mTOR) protein due to dysfunction of the tuberin/hamartin protein
complex, can be rescued by everolimus. Everolimus has been registered as treatment for renal
cell carcinoma and giant cell astrocytoma (SEGA). Evidence in human and animal studies
suggests that mTOR inhibitors improve learning and development in patients with TSC.
Detailed Description
Randomized double-blind placebo controlled intervention study in children with TSC between
age 4 and 15 years with an intelligence quotient (IQ) estimated <80 and/or special schooling
and/or autism spectrum disorder and/or learning disability requiring remedial teaching.
Patients are randomised to receive everolimus or placebo during a period of 12 months.
Study Phase
Phase 2/Phase 3
Study Type
Interventional
Primary Outcome
Cognitive ability measured by IQ
Secondary Outcome
Autistic features
Condition
Tuberous Sclerosis Complex
Intervention
Everolimus
Study Arms / Comparison Groups
Everolimus
Description: Everolimus once daily for 1 year, titration to trough levels of 5-10 ng/ml
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
60
Start Date
November 2012
Completion Date
November 2016
Primary Completion Date
November 2015
Eligibility Criteria
Inclusion Criteria:
- Children with a definite diagnosis of TSC between 4 and 15 years.
- With an IQ estimated <80 and/or special schooling and/or autism spectrum disorder
and/or learning disability requiring remedial teaching.
- Written informed consent by parents/care-takers, and the patient if he or she is 12
years or older and cognitively able to consent.
- In girls after menarche, appropriate contraception must be used or abstinence
practiced.
Exclusion Criteria:
- Hepatic dysfunction
- Surgery <6wk
- Current infection at time of inclusion
- Developmental age estimated below 3.5 years
- Intractable epilepsy with more than 1 seizure/week
- Inability to comply with the treatment protocol
- Additional diseases or disorders that may influence the endpoints, including:
- SEGA requiring treatment
- Uncontrolled diabetes mellitus
- Known impaired lung function
- Allergy for any of the components of the study medication
- Prior treatment with mTOR inhibitors
- HIV seropositivity
- Bleeding diathesis or oral anti-vitamin K medication
- Serum creatinine > 1.5 x ULN
- Uncontrolled hyperlipidemia (fasting serum cholesterol > 7.75 mmol/L, fasting serum
triglycerides > 2.5 x ULN)
- Use of investigational drug within 30 days prior to inclusion
- History of myocardial infarction, angina or stroke related to atherosclerosis, organ
transplantation, malignancy in the past 2 years
- Pregnancy or breastfeeding
- Children at risk for Hepatitis B (HB), unless hepatitis B serology is normal. Risk
groups are children who have lived in Asia, Africa, Central and South America, Eastern
Europe, Spain, Portugal, and Greece, children with known or suspected past or current
hepatitis B infection, current or prior IV illicit drug use, current or prior
dialysis, household contact with hepatitis B infected patient(s), current or prior
high-risk sexual activity, body piercing or tattoos, mother known to have hepatitis B
history. If vaccinated, presence of HBs Ab is normal.
- Known or suspected hepatitis C infection, unless hepatitis C serology is normal.
Gender
All
Ages
4 Years - 15 Years
Accepts Healthy Volunteers
No
Contacts
M.C.Y. de Wit, MD. PhD., +31 10 703 6956, [email protected]
Location Countries
Netherlands
Location Countries
Netherlands
Administrative Informations
NCT ID
NCT01730209
Organization ID
NL38619.078.11
Responsible Party
Principal Investigator
Study Sponsor
Erasmus Medical Center
Collaborators
Utrecht University
Study Sponsor
M.C.Y. de Wit, MD. PhD., Principal Investigator, Erasmus Medical Center
Verification Date
May 2015