Adjunctive Everolimus Treatment of Refractory Epilepsy
Study Details
Study Description
Brief Summary
This project is a prospective, randomized, placebo-controlled, double-blind study that will evaluate the clinical efficacy of everolimus as an adjunctive treatment in adult patients diagnosed with refractory epilepsy.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
The project consists of a screening and baseline monitoring period of 1-2 weeks, and a treatment period of 1 week, followed by a 3-month follow-up period. Approximately 108 participants will be randomized in a blinded manner to one of three arms in a 1:1:1 fashion (everolimus 1h : everolimus 8-9h : Placebo). After screening, participants will have the first video-EEG monitoring for up to 24 hours to assess baseline levels, followed by 1 week of treatment, the second video-EEG monitoring, and a 3-month post treatment follow-up period. During the treatment period, participants will be given everolimus or placebo directed to seizure events. In the "everolimus 1h" group, everolimus will be administrated immediately after seizure events (within 1 hour); while in the "everolimus 8-9h" group, everolimus administration will be delayed (at 8-9 hours after seizure events). We conduct this study to assess the efficacy of everolimus in adult refractory epilepsy patients under an administration strategy in a limited time window immediately after seizure events.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: everolimus 1h The study participants will orally receive everolimus within 1 hour and placebo at 8-9 hours after each seizure event, but with intervals longer than 24 hours. |
Drug: Everolimus
Everolimus will be administrated orally based on seizure events, with an administration interval longer than 24 hours. Participates with a body surface area (BSA) of <= 1.2 m^2, the dosage was 2.5 mg/time; for BSA 1.3-2.1 m^2, the dosage was 5 mg/time; and for BSA >=2.2 m^2, the dosage was 7.5 mg/time.
Other Names:
Drug: Placebo
Vitamin C
|
| Experimental: everolimus 8-9h The study participants will orally receive placebo within 1 hour and everolimus at 8-9 hours after each seizure event, but with intervals longer than 24 hours. |
Drug: Everolimus
Everolimus will be administrated orally based on seizure events, with an administration interval longer than 24 hours. Participates with a body surface area (BSA) of <= 1.2 m^2, the dosage was 2.5 mg/time; for BSA 1.3-2.1 m^2, the dosage was 5 mg/time; and for BSA >=2.2 m^2, the dosage was 7.5 mg/time.
Other Names:
Drug: Placebo
Vitamin C
|
| Placebo Comparator: placebo The study participants will orally receive placebo both within 1 hour and at 8-9 hours after each seizure event, but with intervals longer than 24 hours. |
Drug: Placebo
Vitamin C
|
Outcome Measures
Primary Outcome Measures
- Change from baseline frequency of epileptic discharge [1 week]
Comparing frequency of epileptic discharge during video-EEG monitoring after versus before treatment
Secondary Outcome Measures
- Change from baseline seizure frequency [6 months]
Comparing number of seizures in 3 months after treatment versus baseline
- Change from baseline seizure types [6 months]
Comparing types of seizures in 3 months after treatment versus baseline
- Change from baseline frequency of seizure-free days [6 months]
Comparing seizure-free days in 3 months after treatment versus baseline
- Seizure-free rate [3 months]
Patients remaining seizure free in 3 months after treatment
- Change from baseline occurrence of secondary generalized seizure and status epilepticus [6 months]
Comparing number of occurrence of secondary generalized seizure and status epilepticus in 3 months after treatment versus baseline
- Quality of life questionnaire (QOLIE-31-Chinese version) scores [3 months]
Comparing the scores at 3 months after treatment versus before treatment
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Diagnosis of drug resistant epilepsy, with treatment of at least two approved anti-epileptic drugs (AEDs), and having at least one reported seizure per month during the 3-month baseline phase and no continuous 3-month seizure-free period.
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Diagnosis of focal epilepsy without secondary generalization.
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Treatment with a stable dose of AEDs that must have no drug interactions with everolimus (eg, valproic acid, topiramate, oxazepine, phenobarbital, phenytoin, and primidone) for at least 12 weeks before enrollment.
Exclusion Criteria:
-
History of non-drug treatment for epilepsy, eg, vagus nerve stimulation (VNS), ketogenic diet, and epilepsy surgery.
-
Severe dysfunction in kidney.
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With significant infectious, immunologic, or oncologic comorbidity at the time of enrollment.
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Currently taking or previously treated systemically with an mammilian target of rapamycin (mTOR) inhibitor.
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History of seizures secondary to drug abuse, psychogenic nonepileptic seizures, or an episode of status epilepticus within 1 year before enrollment.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Shengjing Hospital of China Medical University | Shenyang | Liaoning | China | 110004 |
Sponsors and Collaborators
- National Institute on Drug Dependence, China
- Peking University
- Shengjing Hospital
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PKU-SJ-01-2021-V1