EpilepsyEarly Phase 1NCT07095933
The Safety and Efficacy Evaluation of Everolimus as an Adjunctive Treatment for Focal Refractory Epilepsy
A Early Phase 1 study testing Everolimus in people with Epilepsy and Drug Resistant, run by Xuanwu Hospital, Beijing at 1 site in China.
Trial summary
The aim of this study is to evaluate the clinical efficacy of everolimus as an adjunctive therapy for refractory epilepsy. The significance lies in addressing whether the mTOR inhibitor sirolimus has antiepileptic adjunctive effects for a broader range of patients with refractory epilepsy, with the hope of providing a… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Epilepsy, Drug Resistant
- What is being tested?
- Everolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteChina
- Study dates
- 1 Jul 2026to 31 Dec 2026
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Xuanwu Hospital, Beijing
Beijing, Beijing Municipality, 100053
Liankun Ren, MD, +86 13681576621, renlk2022@outlook.com
About this study
Official title: The Safety and Efficacy Evaluation of Everolimus as an Adjunctive Treatment for Focal Refractory Epilepsy: A Pilot Study
The aim of this study is to evaluate the clinical efficacy of everolimus as an adjunctive therapy for refractory epilepsy. The significance lies in addressing whether the mTOR inhibitor sirolimus has antiepileptic adjunctive effects for a broader range of patients with refractory epilepsy, with the hope of providing a new mTOR-targeted antiepileptic adjunctive medication regimen that is administered only during epileptic events and can be widely used for various types of refractory epilepsy.
Read the detailed description
Previous research has shown that the mTOR pathway is involved in the "epilepsy memory" process. Associating the acute seizures of the mouse kainic acid epilepsy model with a specific odor stimulus can lead to specific induction of epileptic seizures by this odor stimulus two weeks later. After epileptic seizures induced by a specific odor stimulus, the expression of the memory-related molecule pmTOR in the mouse hippocampus changes in a time-dependent manner, indicating that the mTOR signaling pathway is involved in the reconsolidation process of epilepsy memory. Further intervention in the reconsolidation process of epilepsy memory with the mTOR inhibitor everolimus (Rap) found that administering the drug within the memory consolidation window (5 min) could effectively intervene in the reinduction of epilepsy, while administering the drug outside the memory consolidation window (9 h) could not intervene. Professor Huang Zhuo's team validated the above experimental results using a conditioned epilepsy memory mouse model. Clinical experiments have found that administering the mTOR pathway inhibitor everolimus immediately after an epileptic seizure in patients can significantly reduce the interictal brain electrical activity, showing promising epilepsy treatment effects. However, this study only involved a single drug treatment, the treatment duration was short, and only the changes in epileptiform discharges after treatment with everolimus in epileptic patients were evaluated at the electrophysiological level, without evaluating the control efficacy on seizure symptoms in patients after repeated seizures with a sufficient course of treatment.
Therefore, inhibiting the mTOR signaling pathway within a specific time window by intervening in the reconsolidation of the current epileptic event holds promise as a new strategy to alleviate subsequent seizures. This strategy is expected to be applicable to a broader range of treatments for refractory epilepsy, and administering medication only during epileptic events is anticipated to achieve more efficient therapeutic effects.
Everolimus (sirolimus) is an inhibitor of the mammalian target of rapamycin (mTOR). In studies using animal models of tuberous sclerosis complex (TSC), mTOR inhibitors have been found to significantly reduce the frequency of epileptic seizures; furthermore, everolimus is currently undergoing phase III clinical trials as an adjunctive treatment for refractory epilepsy associated with TSC. Evidence from various animal models of epilepsy, including genetic epilepsy (such as in WAG/Rij rats) and acquired epilepsy (such as those induced by kainic acid or pilocarpine), also suggests the involvement of the mTOR signaling pathway in these forms of epilepsy and the broad inhibitory effects of mTOR inhibitors on epileptic seizures.
Based on the "epilepsy memory" mechanism, combining everolimus with a memory reconsolidation paradigm holds promise as an effective adjunctive treatment for refractory epilepsy. Evaluating its efficacy and safety not only helps establish its value in epilepsy treatment but also provides important guidance for clinical practice, crucial for the transition from basic research to clinical application.
- Conditions
- Epilepsy, Drug Resistant
- Being tested
- Everolimus
- Keywords
- Everolimus, Focal Refractory Epilepsy, Epilepsy memory, mTOR pathway
- Medical subject headings
- Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EverolimusDrug
Oral administration is given solely for the epilepsy seizure event. Dosage: The dosage is determined based on body surface area (BSA), with 2.5 mg per dose for BSA <1.2 m², 5 mg per dose for BSA 1.3-2.1 m², and 7.5 mg per dose for BSA >2.2 m².
| Study group | Role | What they receive |
|---|---|---|
| Everolimus | Experimental | All subjects will receive the experimental drug. Receives: Drug: Everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change From Baseline in Seizure Frequency Per 28 Days
Percent change in 28-day frequency of seizures during the 12 week treatment and follow-up period relative to baseline
Measured: assessed per 28 days during the treatment until the end of 12-week treatment.
Secondary outcomes (4)
50% Seizure Responder Rate
The proportion of patients with a ≥ 50% reduction from Baseline in seizure frequency.
Measured: Baseline observation period, and 12-week treatment period (ending at 12 weeks).
Seizure Severity
The percent change from baseline in seizure severity evaluated by Liverpool seizure severity scale (LSSS) .
Measured: Baseline observation period, and 12-week treatment period (ending at 12 weeks).
Life quality evaluation
Percentage change from baseline in Quality of Life in Epilepsy-31 inventory (QOLIE-31) score.
Measured: Baseline observation period, and 12-week treatment period (ending at 12 weeks).
Adverse Events
Rate of adverse events which were judged to be study-related throughout the study.
Measured: through study completion, 12 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2025
- Study start1 Jul 2026 (estimated)
- Primary completion1 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EpilepsyStudies of the same condition, open and under way.
- More trials run by Xuanwu Hospital, BeijingThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xuanwu Hospital, Beijing
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Liankun_Ren, Xuanwu Hospital, Beijing
- Investigators
- Liankun Ren, MD, Principal investigator, Xuanwu Hospital, Beijing
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07095933
- Sponsor's protocol ID
- 2025-218-002
- Status last verified
- Apr 2026
- First submitted
- 24 Jul 2025
- Last updated
- 7 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Safety and Efficacy Evaluation of Everolimus as an Adjunctive Treatment for Focal Refractory Epilepsy: A Pilot Study
- ClinicalTrials.gov ID
- NCT07095933
- Acronym / sponsor ID
- 2025-218-002
- Conditions
- Epilepsy, Drug Resistant
- Keywords
- Everolimus, Focal Refractory Epilepsy, Epilepsy memory, mTOR pathway
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 5 participants (estimated)
- Lead sponsor
- Xuanwu Hospital, BeijingUniversity, hospital or other
- Study start
- 1 Jul 2026 (estimated)
- Primary completion
- 1 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 31 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this study is to evaluate the clinical efficacy of everolimus as an adjunctive therapy for refractory epilepsy. The significance lies in addressing whether the mTOR inhibitor sirolimus has antiepileptic adjunctive effects for a broader range of patients with refractory epilepsy, with the hope of providing a new mTOR-targeted antiepileptic adjunctive medication regimen that is administered only during epileptic events and can be widely used for various types of refractory epilepsy.
Detailed description
Previous research has shown that the mTOR pathway is involved in the "epilepsy memory" process. Associating the acute seizures of the mouse kainic acid epilepsy model with a specific odor stimulus can lead to specific induction of epileptic seizures by this odor stimulus two weeks later. After epileptic seizures induced by a specific odor stimulus, the expression of the memory-related molecule pmTOR in the mouse hippocampus changes in a time-dependent manner, indicating that the mTOR signaling pathway is involved in the reconsolidation process of epilepsy memory. Further intervention in the reconsolidation process of epilepsy memory with the mTOR inhibitor everolimus (Rap) found that administering the drug within the memory consolidation window (5 min) could effectively intervene in the reinduction of epilepsy, while administering the drug outside the memory consolidation window (9 h) could not intervene. Professor Huang Zhuo's team validated the above experimental results using a conditioned epilepsy memory mouse model. Clinical experiments have found that administering the mTOR pathway inhibitor everolimus immediately after an epileptic seizure in patients can significantly reduce the interictal brain electrical activity, showing promising epilepsy treatment effects. However, this study only involved a single drug treatment, the treatment duration was short, and only the changes in epileptiform discharges after treatment with everolimus in epileptic patients were evaluated at the electrophysiological level, without evaluating the control efficacy on seizure symptoms in patients after repeated seizures with a sufficient course of treatment.
Therefore, inhibiting the mTOR signaling pathway within a specific time window by intervening in the reconsolidation of the current epileptic event holds promise as a new strategy to alleviate subsequent seizures. This strategy is expected to be applicable to a broader range of treatments for refractory epilepsy, and administering medication only during epileptic events is anticipated to achieve more efficient therapeutic effects.
Everolimus (sirolimus) is an inhibitor of the mammalian target of rapamycin (mTOR). In studies using animal models of tuberous sclerosis complex (TSC), mTOR inhibitors have been found to significantly reduce the frequency of epileptic seizures; furthermore, everolimus is currently undergoing phase III clinical trials as an adjunctive treatment for refractory epilepsy associated with TSC. Evidence from various animal models of epilepsy, including genetic epilepsy (such as in WAG/Rij rats) and acquired epilepsy (such as those induced by kainic acid or pilocarpine), also suggests the involvement of the mTOR signaling pathway in these forms of epilepsy and the broad inhibitory effects of mTOR inhibitors on epileptic seizures.
Based on the "epilepsy memory" mechanism, combining everolimus with a memory reconsolidation paradigm holds promise as an effective adjunctive treatment for refractory epilepsy. Evaluating its efficacy and safety not only helps establish its value in epilepsy treatment but also provides important guidance for clinical practice, crucial for the transition from basic research to clinical application.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Everolimus | Experimental | Drug: EverolimusAll subjects will receive the experimental drug. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EverolimusOral administration is given solely for the epilepsy seizure event. Dosage: The dosage is determined based on body surface area (BSA), with 2.5 mg per dose for BSA <1.2 m², 5 mg per dose for BSA 1.3-2.1 m², and 7.5 mg per dose for BSA >2.2 m². | Drug | Everolimus |
Primary outcome
Percent Change From Baseline in Seizure Frequency Per 28 Days
Time frame: assessed per 28 days during the treatment until the end of 12-week treatment.
Percent change in 28-day frequency of seizures during the 12 week treatment and follow-up period relative to baseline
4 secondary outcomes
50% Seizure Responder Rate
Time frame: Baseline observation period, and 12-week treatment period (ending at 12 weeks).
Seizure Severity
Time frame: Baseline observation period, and 12-week treatment period (ending at 12 weeks).
Life quality evaluation
Time frame: Baseline observation period, and 12-week treatment period (ending at 12 weeks).
Adverse Events
Time frame: through study completion, 12 weeks.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Liankun Ren, MD principal investigator
Xuanwu Hospital, Beijing
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Everolimus in people with Epilepsy and Drug Resistant, run by Xuanwu Hospital, Beijing at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 7 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Liankun Ren, MD (+86 13681576621, renlk2022@outlook.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change From Baseline in Seizure Frequency Per 28 Days (time frame: assessed per 28 days during the treatment until the end of 12-week treatment.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Apr 2026.