Efficacy of RAD001/Everolimus in Autism and NeuroPsychological Deficits in Children With Tuberous Sclerosis Complex

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 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

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