Behaviors and Mental Disorders

All Conditions

Symptoms and General Pathology

Nervous System Diseases

Neoplasms

Diseases and Abnormalities at or Before Birth

Skin and Connective Tissue Diseases

Rare Diseases

Autistic Disorder

Sclerosis

Intellectual Disability

Tuberous Sclerosis

Autism Spectrum Disorder

Child Development Disorders, Pervasive

Developmental Disabilities

Neurodevelopmental Disorders

Mental Disorders

Psychotic Disorders

Hamartoma

Neoplasms, Multiple Primary

Syndrome

Neoplastic Syndromes, Hereditary

Congenital Abnormalities

Malformations of Cortical Development

Nervous System Malformations

Neurocutaneous Syndromes

Heredodegenerative Disorders, Nervous System

Neurodegenerative Diseases

Genetic Diseases, Inborn

Tuberous Sclerosis Complex

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Everolimus

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

Everolimus once daily for 1 year, titration to trough levels of 5-10 ng/ml

Placebo treatment for 1 year. Tablets will be identical to everolimus tablets.

Everolimus once daily titrated to trough levels of 5-10 ng/ml.

Placebo

M.C.Y. de Wit, MD. PhD.

I.E. Overwater, MSc

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.

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.

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

Assessed by the school CITO (centraal instituut voor toetsontwikkeling) scores or reading and arithmetic scores

Assessed by measuring trough levels of everolimus

Levels of and abnormalities in blood control values

Assessed by Wechsler scales: Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III NL) and Wechsler Intelligence Scale for Children (WISC-III-NL)

Assessed by Autism Diagnostic Observation Schedule (ADOS)

Assessed by social responsiveness scale (SRS) and Dutch Children's Communication Checklist (CCC-2-NL) questionnaires

Assessed by Cambridge Neuropsychological Test Automated Battery (CANTAB)

Assessed by BEERY Visual-Motor Integration (BEERY VMI), grooved pegboard

Assessed by Child Behavior Checklist (CBCL) and Teacher's Report Form (TRF) questionnaires

Assessed by Behavior Rating Inventory of Executive Functioning (BRIEF) questionnaire Dutch version

Assessed by Sleep Disturbance Scale for Children (SDSC) questionnaire

Assessed by Child Health Questionnaire Parent Form (CHQ-PF50) questionnaire

Assessed by Short Sensory Profile (SSP) questionnaire

Comparison of epilepsy frequency during month previous to study start and last month of trial participation.

EEG abnormalities

Spots Global Cancer Trial Database for tsc related cognitive disability