Adjunctive Everolimus Treatment of Refractory Epilepsy

National Institute on Drug Dependence, China

Status and phase: Enrolling; Phase 2

Conditions: Epilepsy

Treatments: Drug: Everolimus; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT05613166

PKU-SJ-01-2021-V1

Details and patient eligibility

About

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.

Full 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.

Enrollment: 108 estimated patients

Sex: All

Ages: 19+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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108 participants in 3 patient groups, including a placebo group

everolimus 1h

Experimental group

Description:

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.

Treatment:

Drug: Everolimus

Drug: Placebo

everolimus 8-9h

Experimental group

Description:

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.

Treatment:

Drug: Everolimus

Drug: Placebo

placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo