Adjunctive Everolimus Treatment of Refractory Epilepsy

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Prospective, Randomized, Double-blind, Placebo-Controlled Phase Ⅱ Study to Evaluate the Efficacy of Adjunctive Everolimus Treatment in Patients With Refractory Epilepsy

Conditions
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Epilepsy

Intervention / Treatment
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* Drug: Everolimus
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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. Diagnosis of focal epilepsy without secondary generalization. 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. With significant infectious, immunologic, or oncologic comorbidity at the time of enrollment. Currently taking or previously treated systemically with an mammilian target of rapamycin (mTOR) inhibitor. History of seizures secondary to drug abuse, psychogenic nonepileptic seizures, or an episode of status epilepticus within 1 year before enrollment.

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: everolimus 1h<br>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<br>* 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.<br>* Other names: Afinitor;Drug: Placebo<br>* Vitamin C<br>|
| Experimental: everolimus 8-9h<br>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<br>* 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.<br>* Other names: Afinitor;Drug: Placebo<br>* Vitamin C<br>|
| Placebo Comparator: placebo<br>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<br>* Vitamin C<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline frequency of epileptic discharge | Comparing frequency of epileptic discharge during video-EEG monitoring after versus before treatment | 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline seizure frequency | Comparing number of seizures in 3 months after treatment versus baseline | 6 months | 
| Change from baseline seizure types | Comparing types of seizures in 3 months after treatment versus baseline | 6 months | 
| Change from baseline frequency of seizure-free days | Comparing seizure-free days in 3 months after treatment versus baseline | 6 months | 
| Seizure-free rate | Patients remaining seizure free in 3 months after treatment | 3 months | 
| Change from baseline occurrence of secondary generalized seizure and status epilepticus | Comparing number of occurrence of secondary generalized seizure and status epilepticus in 3 months after treatment versus baseline | 6 months | 
| Quality of life questionnaire (QOLIE-31-Chinese version) scores | Comparing the scores at 3 months after treatment versus before treatment | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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everolimus