Everolimus (RAD001) Therapy for Epilepsy in Patients With Tuberous Sclerosis Complex (TSC)
The goal of this study is to learn if the study drug RAD001 can reduced the number of epileptic seizures, and can be taken safety by people who have epilepsy associated with Tuberous Sclerosis Complex.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Everolimus (RAD001) Therapy for Epilepsy in Patients With Tuberous Sclerosis Complex|
- The percentage of subjects with reduction in seizure frequency [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
- Number of subjects continuing study medication over time [ Time Frame: Individual subjects will be assessed every 6 months, aggregate analysis will take place at end of study ] [ Designated as safety issue: No ]
|Study Start Date:||March 2015|
|Estimated Study Completion Date:||March 2020|
|Estimated Primary Completion Date:||March 2019 (Final data collection date for primary outcome measure)|
Subjects will be administered study drug if they meet study criteria after 4 weeks of baseline phase. The starting dose will be 5 mg/m2/day, rounded to the nearest 2.5 mg/dose, to be taken daily.
Everolimus is available in tablet form. The starting dose will be 5 mg/m2/day, rounded to the nearest 2.5 mg/dose, to be taken daily. After two weeks, serum trough level will be measured and dose adjusted according to the following algorithm If Blood trough level is less than 2.5 ng/ml than increase dose by 5 mg/m2/day; If Blood trough level is 2.5-5.0 ng/ml than increase dose by 2.5 mg/m2/day; If Blood trough level is 5.1-10.0 ng/ml than increase dose by 0 mg/m2/day (no change); If Blood trough level is 10.1-15.0 ng/ml than decrease dose by 2.5 mg/m2/day
Tuberous sclerosis complex (TSC) is a genetic disorder with an incidence at birth of 1 in 6000. This disorder is characterized by the development of benign tumors in multiple organ systems, including the brain. The primary neurological manifestations of TSC are epilepsy, mental retardation and autism. Epilepsy is most common, occurring in 80-90% of patients, and often the seizures are severe, unremitting, and uncontrolled by current anticonvulsant medications. It is generally accepted that the seizures arise from cortical and subcortical tubers and surrounding tissue in the brain. These tubers are caused by mutations in the tumor suppressor genes TSC1 or TSC2. The protein products of these genes, hamartin and tuberin, act as negative regulators of the PI3K/PKB(Akt)/mTOR signaling pathway that regulates cell growth and proliferation Everolimus is an immunosuppressant drug that also inhibits mTOR signaling and is capable of reversing aberrant mTOR-dependent effects that occur when hamartin or tuberin are absent or defective. Thus, we hypothesize that drugs like everolimus may be therapeutically useful for the treatment of refractory epilepsy in patients with TSC.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01070316
|United States, Ohio|
|Cincinnati Children's Hospital Medical Center|
|Cincinnati, Ohio, United States, 45229|
|United States, Texas|
|Baylor College of Medicine|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Darcy Krueger, M.D. Ph.D||Children's Hospital Medical Center, Cincinnati|