Everolimus added to treatment for focal drug-resistant epilepsy

The Safety and Efficacy Evaluation of Everolimus as an Adjunctive Treatment for Focal Refractory Epilepsy: A Pilot Study

This trial will test whether giving the mTOR inhibitor everolimus shortly after seizures can help reduce further seizures and abnormal brain activity in adults with focal drug‑resistant epilepsy.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 5 (estimated)
• Ages: 18 Years to 60 Years
• Sex: All
• Sponsor: Xuanwu Hospital, Beijing (Academic / other)
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT07095933 on ClinicalTrials.gov

What this trial studies

This is an early-phase interventional trial testing everolimus as an adjunctive therapy delivered around the time of focal seizures in adults with drug‑resistant epilepsy. The design builds on animal experiments showing mTOR pathway involvement in 'epilepsy memory' and that timed administration of an mTOR inhibitor can block reinduction of seizures. Prior limited clinical observations reported reductions in interictal EEG activity after single doses, but treatment durations were short and effects on clinical seizure recurrence remain unproven. The trial enrolls adults 18–60 with frequent focal seizures and confirmed focal epilepsy by EEG or imaging, and is conducted at Xuanwu Hospital in Beijing.

Who should consider this trial

Good fit: Adults 18–60 with focal drug‑resistant epilepsy who have had at least 16 focal seizures in the 8‑week baseline and EEG or imaging consistent with focal epilepsy are the intended participants.

Not a fit: People with generalized epilepsy, progressive central nervous system lesions, too few seizures during baseline, or who are outside the 18–60 age range are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could reduce seizure recurrence and abnormal interictal brain activity when given as a brief adjunct after focal seizures.

How similar studies have performed: Preclinical mouse models and small clinical observations suggest mTOR inhibitors can reduce epileptiform activity, but using everolimus as a seizure‑timed adjunct is a novel approach that has not yet been validated in larger trials.

Eligibility criteria

Inclusion Criteria:

* Age between 18 and 60 years (inclusive), regardless of sex.
* Diagnosis of epilepsy, meeting the criteria for focal seizures or focal to bilateral tonic-clonic seizures as defined by the 2017 International League Against Epilepsy (ILAE) classification.
* History of epileptic seizures lasting ≥30 seconds, accompanied by impaired awareness.
* At least 16 focal seizures during the 8-week baseline period prior to enrollment, with no seizure-free interval of 21 consecutive days.
* Findings on electroencephalography (EEG) or neuroimaging (MRI or CT) performed within 2 years prior to screening consistent with a diagnosis of focal epilepsy, and exclusion of progressive structural central nervous system lesions or progressive encephalopathy.
* Diagnosis of drug-resistant epilepsy, defined as failure to achieve sustained seizure freedom despite adequate trials of at least two appropriately chosen and tolerated antiseizure medications (ASMs) over a period of 2 years. - Existing ASMs must have no known drug-drug interactions with everolimus and must have been administered at a stable dose for at least 12 weeks prior to enrollment.
* Use of vagus nerve stimulation (VNS) or deep brain stimulation (DBS) is permitted, provided the device was implanted at least 5 months prior to screening, with stimulation parameters stable for at least 12 weeks before enrollment and maintained unchanged throughout the study.
* Written informed consent to participate in the study, provided voluntarily by the subject.
* In the investigator's judgment, the subject is able to comply with the requirements of the study protocol, including understanding and completing seizure diaries, adhering to the visit schedule, and taking study medications as directed.

Exclusion Criteria:

* Diagnosis of primary generalized epilepsy.
* History of non-epileptic events (e.g., psychogenic non-epileptic seizures).
* Patients with only non-motor focal seizures according to the 2017 ILAE classification.
* Epilepsy with identifiable and treatable causes (e.g., metabolic disorders, intoxication, infection, space-occupying lesions, or confirmed genetic abnormalities).
* Inability to accurately count seizures due to excessively frequent episodes within the 12 months prior to study drug administration.
* History of epileptic seizure clusters within the 12 months prior to study drug administration.
* History of status epilepticus within the 12 months prior to study drug administration.
* Use of mTOR pathway inhibitors within the 12 months prior to study drug administration.
* History of cerebrovascular events (e.g., cerebral infarction, cerebral hemorrhage, or transient ischemic attack) or progressive intracranial lesions within the 6 months prior to study drug administration.
* Presence of severe uncontrolled diseases, including immunodeficiency disorders, hepatic or renal disease, acute infection, significant pulmonary dysfunction, or advanced malignancy.
* Severe cardiovascular or peripheral vascular disease, such as New York - Heart Association (NYHA) class III-IV heart failure, malignant arrhythmias (e.g., long QT syndrome, Brugada syndrome, conduction block), any other clinically significant ECG abnormalities, or myocardial infarction within 3 months prior to screening.
* History of any condition or surgery that, in the investigator's opinion, could affect absorption, distribution, or metabolism of the study drug (e.g., active gastric ulcer, ulcerative colitis, Crohn's disease, intestinal obstruction), or presence of dysphagia.
* Any medical condition, psychiatric disorder, cognitive impairment, or intellectual disability that, in the investigator's judgment, may increase the risk to the subject or interfere with study participation.
* Laboratory abnormalities meeting any of the following criteria: alanine aminotransferase (ALT) \>2× upper limit of normal (ULN), aspartate aminotransferase (AST) \>2× ULN, alkaline phosphatase (ALP) \>2× ULN, platelet count \<80×10⁹/L, neutrophil count \<1.8×10⁹/L, or creatinine clearance (CLcr) \<30 mL/min (calculated by the Cockcroft-Gault formula).
* Female subjects who test positive for pregnancy during screening or who are breastfeeding.
* History of alcohol or substance abuse within 2 years prior to study drug administration.
* Participation in any other clinical trial within 3 months prior to study drug administration, except for non-interventional clinical trials.
* Known hypersensitivity or allergy to any component of everolimus tablets.
* Current use of medications that may affect the central nervous system or the metabolism of everolimus.

Where this trial is running

Beijing, Beijing Municipality

• Xuanwu Hospital, Beijing — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Principal investigator: Liankun Ren, MD — Xuanwu Hospital, Beijing
• Study coordinator: Liankun Ren, MD

Conditions Epilepsy; Drug Resistant; Everolimus; Focal Refractory Epilepsy; Epilepsy memory; mTOR pathway