Clinical trial NCT05613166: Adjunctive Everolimus Treatment of Refractory Epilepsy
Official title: A Prospective, Randomized, Double-blind, Placebo-Controlled Phase Ⅱ Study to Evaluate the Efficacy of Adjunctive Everolimus Treatment in Patients With Refractory Epilepsy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Epilepsy
Keywords: everolimus
Lead sponsor: National Institute on Drug Dependence, China
Sponsor class: OTHER
Collaborators: name: Peking University
name: Shengjing Hospital
First posted: 2022-11-14
Enrollment: 108
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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.
* 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.

Primary outcomes:
measure: Change from baseline frequency of epileptic discharge
timeFrame: 1 week
Secondary outcomes:
measure: Change from baseline seizure frequency
timeFrame: 6 months
measure: Change from baseline seizure types
timeFrame: 6 months
measure: Change from baseline frequency of seizure-free days
timeFrame: 6 months
measure: Seizure-free rate
timeFrame: 3 months
measure: Change from baseline occurrence of secondary generalized seizure and status epilepticus
timeFrame: 6 months
measure: Quality of life questionnaire (QOLIE-31-Chinese version) scores
timeFrame: 3 months
Other outcomes:
Locations:
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
state: Liaoning
Study officials:
References: