focal cortical dysplasia (type-II)
Conditions
Interventions
The investigational drug (sirolimus) is orally administered once a day with the following doses: <
Dose adjustment period>
Initial amount: 1 mg/day for body weight of less than 40 kg, and 2 mg/day for 40 kg or more. Dose adjustment: to increase as necessary to adjust the trough concentration of sirolimus to the range of
Maintenance therapy period>
To adopt dosage regimen and dose of sirolimus at trough concentration of 5-15 ng/ml.
Sponsors
Hokkaido University Hospital Nishi-Niigata Chuo National Hospital National Center Hospital, NCNP Shizuoka Institute of Epilepsy and Neurological Disorders Okayama University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Diagnosed with pathologically localized cortical dysplasia type-II by neuroimaging findings in head MRI within 156 weeks prior to enrollment or brain pathology examination before enrollment. 2. Aged 6 to 65 years at the time of informed consent. 3. Diagnosed with a partial seizure (a simple partial seizure with motor signs which can be objectively diagnosed, a complex partial seizure, or a secondarily generalized seizure) based on the 1981 epileptic seizure type international classification of the International League Against Epilepsy (ILAE). 4. Having treated for at least 52 weeks with two or more antiepileptic drugs after diagnosis with epilepsy. 5. Under treatment with 1 to 4 antiepileptic drugs. 6. Whose dose and regimen of antiepileptic drug are constant from the 8th week before enrollment, or whose stimulation condition is constant from the 8th week before enrollment in case of performing vagus nerve stimulation therapy. 7. With two or more partial seizures (including secondarily generalized seizures) during the baseline observation period of 28 days. 8. Provided written consent by themselves/parent or legal representatives.
Exclusion criteria
Exclusion criteria: 1. Those participated in other trials within 12 weeks before the time of consent. 2. Having used sirolimus or everolimus within 52 weeks before enrollment. 3. Who cannot accurately record the number and time of epileptic seizures by themselves/representatives. 4. Suspected of progressive lesions in CT or MRI. 5. Having underwent cerebral surgery for epilepsy within 28 weeks prior to enrollment. 6. Taking Felbamate or Vigabatrine or having taken it within 28 weeks before enrollment. 7. Under ketogenic diet therapy. 8. Having suicide attempts in the past. 9. With a history or complications of substance abuse including alcohol abuse. 10. Those possibly pregnant and cannot perform contraception during the study period (including partners), pregnant or lactating. 11. Falling under any of the following in clinical examination during baseline observation period: - At least 2.5 times the reference value of AST or ALT - WBC count of less than 3,000/micro L, Ht of less than 30%, platelets of less than 80,000/micro L, or neutrophil counts of less than 1,000/ micro L - Ccr of less than 50 ml/min - HBs antigen-positive, HBs antibody-positive except after vaccination with hepatitis B vaccine, or HBc antibody-positive. Or active hepatitis C excluding inactive cases with normal liver function. - In poor control of dyslipidemia with serum triglycerides of 500 mg/dL or more, or LDL cholesterol of 190 mg/dL or more despite being treated for dyslipidaemia. - With renal dysfunction. (eGFR of less than 30 ml/min/1.73 m2) 12. With complications of arrhythmia requiring treatment. 13. With complications of heart/renal failure that may affect hemodynamics. 14. With immunodeficiency complications. 15. Having underwent surgery (surgery requiring invasion into a body cavity or surgery requiring suture of three or more needles including biopsy) within 12 weeks before enrollment. 16. Judged inappropriate for participating in this study by the principal investigator/sub-investigators.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| A reduction rate of incidence of partial seizures (including secondarily generalized seizures) per 28 days during maintenance therapy from the observation period | — |
Secondary
| Measure | Time frame |
|---|---|
| - Change in incidence of general seizures per 28 days during maintenance therapy from the observation period - Change in incidence epileptic spasm per 28 days during maintenance therapy from the observation period - Change in incidence of heavy-weight attacks per 28 days during maintenance period from the observation period - A response rate (proportion of cases in which incidence of seizures during maintenance therapy decreased by 50% or more from the observation period) - Proportion of resolution of partial seizures during maintenance therapy - A decrease rate and a response rate of incidence of partial seizures at 4 weeks, 8 weeks, and 12 weeks in the maintenance therapy from the observation period - Adverse events | — |
Countries
Japan
Contacts
Public ContactKenji Nagaya
National Hospital Organization Nagoya Medical Center Department of Clinical Research Planning and Management, Clinical Research Center
Outcome results
None listed