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Adjunctive Everolimus Treatment of Refractory Epilepsy

Phase 2
Recruiting
Conditions
Epilepsy
Interventions
Drug: Placebo
Registration Number
NCT05613166
Lead Sponsor
National Institute on Drug Dependence, China
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.

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
108
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
everolimus 1hPlaceboThe 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.
placeboPlaceboThe 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.
everolimus 8-9hPlaceboThe 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.
everolimus 1hEverolimusThe 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.
everolimus 8-9hEverolimusThe 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.
Primary Outcome Measures
NameTimeMethod
Change from baseline frequency of epileptic discharge1 week

Comparing frequency of epileptic discharge during video-EEG monitoring after versus before treatment

Secondary Outcome Measures
NameTimeMethod
Change from baseline frequency of seizure-free days6 months

Comparing seizure-free days in 3 months after treatment versus baseline

Change from baseline seizure frequency6 months

Comparing number of seizures in 3 months after treatment versus baseline

Change from baseline seizure types6 months

Comparing types of seizures in 3 months after treatment versus baseline

Change from baseline occurrence of secondary generalized seizure and status epilepticus6 months

Comparing number of occurrence of secondary generalized seizure and status epilepticus in 3 months after treatment versus baseline

Seizure-free rate3 months

Patients remaining seizure free in 3 months after treatment

Quality of life questionnaire (QOLIE-31-Chinese version) scores3 months

Comparing the scores at 3 months after treatment versus before treatment

Trial Locations

Locations (1)

Shengjing Hospital of China Medical University

🇨🇳

Shenyang, Liaoning, China

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