Clinical trial NCT01289912
Conditions: Tuberous Sclerosis Complex
Keywords: Tuberous Sclerosis Complex Autism Neurocognition RAD001 Everolimus Afinitor TSC
Sponsor: Mustafa Sahin
Start date: 2011-01-01; Completion date: 2014-12-01
Enrollment: 52 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Tuberous Sclerosis Complex (TSC) is a multi-system disease, usually presenting with seizures, mental retardation and autism, and exhibiting a high variability in clinical findings both among and within families. Investigators are doing research in order to identify possible neurocognitive benefits from treatment with RAD001 or placebo for a six month period. There may also be potential for improvements in seizure frequency, sleep and autistic behaviors. We hope this trial will lead to a better understanding of TSC and to new forms of treatment, to benefit children and adults with TSC in the future.

Individuals diagnosed with TSC will be asked to participate in this study if they are between the ages of 6 and 21 years of age and have an IQ of greater than or equal to 60. Both males and females will be asked to participate. Additionally, to be eligible for study participation, individuals must have been on the same seizure medication(s), if applicable, for at least 6 months. Individuals must also be able to participate in neuropsychological testing and meet certain medical criteria. They will need to sign an informed consent. If enrolled in the study, participants will have a number of screening tests to help determine if they are eligible for participation in the clinical trial. If eligible for the treatment phase of the trial, they will be asked to take either the study drug or a placebo (pill with no medicine), which is determined by chance.

The study involves about 9 visits, 3 of which can be done locally, over a six month period, as well as follow-up calls with our research nurse. Study visits will vary in length. Screening, three month and six month visits may last up to 8 hours, while all other visits will be less than 2 hours. The study visits include blood draws, laboratory tests and neuropsychological assessments. There is no fee to participate in this study. The study drug will be provided at no charge during the study.

After all study data has been analyzed, families will be informed of the overall results. Treatment on this study may or may not improve a child's learning skills (neurocognition). Future patients may benefit from what is learned.

Detailed description:
This is a signal-seeking Phase II randomized, placebo-controlled trial of RAD001 in children and young adults with TSC with neurocognition as the primary outcome and autism spectrum disorder as a secondary outcome.

Specific Aims /Objectives Primary objective

* To evaluate the efficacy of RAD001 on neurocognition in patients with TSC compared to placebo as measured by well-validated, standardized, direct and indirect neurocognitive tools.
* To evaluate the safety of RAD001 compared with placebo in patients with TSC focusing on NCI CTCAE Grade 3 and 4 adverse events, serious adverse events, and Grade 3 and 4 laboratory toxicities.

Secondary objectives

* Comparison of absolute change from baseline in frequency of epileptiform events as recorded on seizure diaries between patients taking RAD001 vs. placebo
* Comparison of sleep disturbances between patients taking RAD001 vs. placebo, measured by the Pediatric Sleep Questionnaire (PSQ) and sleep logs
* Comparison of autism spectrum disorders features between patients taking RAD001 vs. placebo, measured by ADOS and SRS
* Comparison of academic skills between patients taking RAD001 vs. placebo, measured by WRAT4
* Comparison of behavioral problems between patients taking RAD001 vs placebo, measured by behavioral rating scales (BRIEF, BASC, SDQ, CHQ and SRS)

Arms: arm 1: 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. arm 2: Matching placebo will be provided as a matching tablet and will also be blister packed under aluminum foil in units of 10.
Interventions: intervention 1: RAD001 intervention 2: Placebo
Intervention descriptions: intervention 1: 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 in the morning after a light, nonfat breakfast. intervention 2: 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 in the morning after a light, nonfat breakfast.

Protocol documents: