Using sirolimus to treat drug-resistant focal epilepsy

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

This study is testing if sirolimus can help people with drug-resistant epilepsy by reducing the number of seizures they have.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 18 Years to 60 Years
• Sex: All
• Sponsor: Xuanwu Hospital, Beijing (Academic / other)
• Locations: 1 site (Beijing)
• Trial ID: NCT06719791 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness of sirolimus as an additional treatment for patients with refractory epilepsy. It focuses on the mTOR signaling pathway, which has been implicated in the memory processes related to epilepsy. The approach involves administering sirolimus during or shortly after epileptic seizures to potentially reduce their recurrence. The study aims to provide a new treatment option for a broader range of patients suffering from this condition.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-60 with refractory focal epilepsy who have not responded to at least two anti-epileptic drugs.

Not a fit: Patients with generalized or hereditary epilepsy may not benefit from this treatment.

Why it matters

Potential benefit: If successful, this treatment could offer a new adjunctive therapy for patients with drug-resistant focal epilepsy, improving seizure control.

How similar studies have performed: Previous studies have shown promising results with mTOR inhibitors like everolimus in treating epilepsy, suggesting potential for success with sirolimus.

Eligibility criteria

Inclusion Criteria:

* 18-60 years of age.
* Meet the 2017 International League Against Epilepsy (ILAE) diagnostic criteria for for focal seizures or focal seizures progressing to bilateral tonic-clonic seizures.
* Diagnosed with refractory epilepsy, having used at least two AEDs without effectiveness for 2 years. No drug interaction between current AEDs and sirolomus, and a stable dose for at least 12 weeks prior to enrollment.
* Seizure duration ≥1 minute, with accompanying sensory impairment.
* At least 6 focal seizures within the 12 weeks preceding enrollment.
* EEG or MRI/CT results within the past 2 years, confirming the diagnosis of focal epilepsy.
* The use of vagus nerve stimulation (VNS) and deep brain stimulation (DBS) is permitted, need to implant at least 5 months and stable for at least 12 weeks before enrollment.The parameters should keep unchanged until the end of the study.
* Informed consent signed.

Exclusion Criteria:

* Diagnosed with generalized or hereditary epilepsy with ion channel gene mutations
* Psychogenic non-epileptic seizures within 12 months;
* Treatable causes of epilepsy (such as metabolic disorders, toxicity, infections, space occupying lesions, or identified genetic abnormalities)
* Patients with only non-motor focal seizures, as classified by the 2017 ILAE.
* Seizure clusters within the 12 months.
* Tonic-clonic status epilepticus within12 months.
* Free of major medical illnesses including:
* Cerebrovascular events within the past 6 months, including cerebral infarction, cerebral hemorrhage, and transient ischemic attack, or those with progressive intracranial lesions.
* Severe uncontrolled diseases, such as immunodeficiency disorders, liver or kidney diseases, acute infections, or advanced-stage tumors.
* Severe cardiovascular or peripheral vascular diseases, such as those classified as NYHA Class III-IV, or those with malignant arrhythmias (e.g., Long QT syndrome, Brugada syndrome, and conduction block), or any other clinically significant electrocardiogram abnormalities, or who have had a myocardial infarction within the past 3 months before screening
* Participants with a history of medical conditions or surgeries that, in the investigator's judgment, could affect the absorption, distribution, or metabolism of the study drug (e.g., active peptic ulcers, ulcerative colitis, Crohn's disease, or bowel obstruction) or those with difficulty swallowing.
* Participants with any medical condition, mental health status, cognitive impairment, or intellectual disability that the investigator believes could increase the risk to the participant or interfere with their ability to participate in the clinical trial.
* Severe allergic reactions to any component of sirolimus, or have hypersensitivity.
* Participants meeting any of the following laboratory criteria: alanine aminotransferase (ALT) \>2× upper limit of normal (ULN), aspartate aminotransferase (AST) \>2× ULN, alkaline phosphatase (ALP) \>2× ULN, platelet count \<80×10\^9/L, neutrophil count \<1.8×10\^9/L, or creatinine clearance (CLcr) \<30 mL/min (calculated by the Cockcroft-Gault formula).
* In the period of pregnancy, childbirth, lactation.
* Alcohol abuse or drug misuse within 2 years prior to medication.
* Participation in another clinical study within 3 months;

Where this trial is running

Beijing

• Xuanwu Hospital — Beijing, China (Recruiting)

Study contacts

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

Conditions Epilepsy, Drug Resistant; Sirolomus; Focal Refractory Epilepsy; mTOR pathway