Adjunctive Everolimus Treatment of Refractory Epilepsy

Epilepsy Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05613166
• Other study ID #: PKU-SJ-01-2021-V1
• Status: Recruiting
• Phase: Phase 2
• Start date: November 2022
• Est. completion date: March 2023

Study information

• Verified date: November 2022
• Source: National Institute on Drug Dependence, China
• Contact: Weining Ma, MD.
• Phone: 86-024-96615-36316
• Email: maweining1985[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 108
• Est. completion date: March 2023
• Est. primary completion date: January 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Drug Resistant Epilepsy
• Epilepsy

Intervention

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.
• Placebo
Vitamin C

Locations

Country	Name	City	State
China	Shengjing Hospital of China Medical University	Shenyang	Liaoning

Sponsors (3)

Lead Sponsor	Collaborator
National Institute on Drug Dependence, China	Peking University, Shengjing Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline frequency of epileptic discharge	Comparing frequency of epileptic discharge during video-EEG monitoring after versus before treatment	1 week
Secondary	Change from baseline seizure frequency	Comparing number of seizures in 3 months after treatment versus baseline	6 months
Secondary	Change from baseline seizure types	Comparing types of seizures in 3 months after treatment versus baseline	6 months
Secondary	Change from baseline frequency of seizure-free days	Comparing seizure-free days in 3 months after treatment versus baseline	6 months
Secondary	Seizure-free rate	Patients remaining seizure free in 3 months after treatment	3 months
Secondary	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
Secondary	Quality of life questionnaire (QOLIE-31-Chinese version) scores	Comparing the scores at 3 months after treatment versus before treatment	3 months