Epilepsy, Drug ResistantEarly Phase 1NCT06719791
Sirolomus Adjuvant Treatment of Focal Refractory Epilepsy (SATFRE)
A Early Phase 1 study testing Sirolimus in people with Epilepsy, 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 sirolimus 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?
- Sirolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteChina
- Study dates
- 23 Dec 2024to 1 Dec 2028
- 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
- 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.
Who cannot join
- 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.
Show all 17Show fewer
- 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;
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: The Safety and Efficacy Evaluation of Sirolomus as an Adjunctive Treatment for Focal Refractory Epilepsy: A Pilot Study
The aim of this study is to evaluate the clinical efficacy of sirolimus 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 sirolimus (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
- Sirolimus
- Keywords
- Sirolomus, Focal Refractory Epilepsy, mTOR pathway
- Medical subject headings
- Drug Resistant Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirolimusDrug
Oral administration is given solely for the epilepsy seizure event. Dosage: The dosage is determined based on body surface area (BSA), with 0.5 mg per dose for BSA <1.2 m², 1 mg per dose for BSA 1.3-2.1 m², and 1.5 mg per dose for BSA >2.2 m².
| Study group | Role | What they receive |
|---|---|---|
| Open label single arm, drug sirolomus | Experimental | All subjects will receive the experimental drug Receives: Drug: Sirolimus |
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 40 week treatment and follow-up period relative to baseline
Measured: assessed per 28 days during the treatment.
50% Seizure Responder Rate
The proportion of patients with a ≥ 50% reduction from Baseline in seizure frequency.
Measured: short-term treatment period (ending at 3 months); long-term follow-up period (ending at 12 months).
Secondary outcomes (3)
Seizure Severity
The percent change from baseline in seizure severity evaluated by Liverpool seizure severity scale (LSSS) .
Measured: Baseline observation period; short-term treatment period (ending at 3 months); long-term follow-up period (ending at 12 months).
Life quality evaluation
Percentage change from baseline in Quality of Life in Epilepsy-31 inventory (QOLIE-31) score.
Measured: Baseline observation period; short-term treatment period (ending at 3 months); long-term follow-up period (ending at 12 months).
Adverse Events
Rate of adverse events which were judged to be study-related throughout the study.
Measured: through study completion, 12 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2024
- Study start23 Dec 2024
- Primary completion1 Dec 2027 (estimated)
- Study completion1 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Epilepsy, Drug ResistantStudies 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
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xuanwu Hospital, Beijing
- Sponsor type
- University, hospital or other
- Collaborators
- Peking University
- Responsible party
- Principal investigator, Liankun_Ren, Xuanwu Hospital, Beijing
- Investigators
- Liankun Ren, MD, Principal investigator, Xuanwu Hospital, BeijingZhuo Huang, PhD, Principal investigator, Peking University School of Pharmaceutical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06719791
- Sponsor's protocol ID
- 2024-259-002
- Status last verified
- Dec 2024
- First submitted
- 1 Dec 2024
- Last updated
- 31 Dec 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Safety and Efficacy Evaluation of Sirolomus as an Adjunctive Treatment for Focal Refractory Epilepsy: A Pilot Study
- ClinicalTrials.gov ID
- NCT06719791
- Acronym / sponsor ID
- 2024-259-002
- Conditions
- Epilepsy, Drug Resistant
- Keywords
- Sirolomus, Focal Refractory Epilepsy, mTOR pathway
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Xuanwu Hospital, BeijingUniversity, hospital or other
- Collaborators
- Peking University
- Study start
- 23 Dec 2024 (actual)
- Primary completion
- 1 Dec 2027 (estimated)
- Study completion
- 1 Dec 2028 (estimated)
- First posted
- 6 Dec 2024 (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 sirolimus 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 sirolimus (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 |
|---|---|---|
| Open label single arm, drug sirolomus | Experimental | Drug: SirolimusAll 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 (8 listed)
- 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.
Key exclusion criteria (17 listed)
- 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.
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 |
|---|---|---|
| SirolimusOral administration is given solely for the epilepsy seizure event. Dosage: The dosage is determined based on body surface area (BSA), with 0.5 mg per dose for BSA <1.2 m², 1 mg per dose for BSA 1.3-2.1 m², and 1.5 mg per dose for BSA >2.2 m². | Drug | Open label single arm, drug sirolomus |
Primary outcome
Percent Change From Baseline in Seizure Frequency Per 28 Days
Time frame: assessed per 28 days during the treatment.
Percent change in 28-day frequency of seizures during the 40 week treatment and follow-up period relative to baseline
50% Seizure Responder Rate
Time frame: short-term treatment period (ending at 3 months); long-term follow-up period (ending at 12 months).
The proportion of patients with a ≥ 50% reduction from Baseline in seizure frequency.
3 secondary outcomes
Seizure Severity
Time frame: Baseline observation period; short-term treatment period (ending at 3 months); long-term follow-up period (ending at 12 months).
Life quality evaluation
Time frame: Baseline observation period; short-term treatment period (ending at 3 months); long-term follow-up period (ending at 12 months).
Adverse Events
Time frame: through study completion, 12 months.
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 31 Dec 2024.
Related trials for Epilepsy, Drug Resistant
Not yet recruiting
Clinical Trial of SEEG for Drug-resistant Epilepsy
Drug-Resistant Epilepsy
Recruiting
Identification of Biomarkers for Vagus Nerve Stimulation in Patients With Refractory Epilepsy
Refractory Epilepsy
RecruitingPhase 1
A Phase I Clinical Trial of UX-GIP001 in the Treatment of Drug-Resistant Unilateral Mesial Temporal Lobe Epilepsy
Epilepsy
Not yet recruiting
Electrophysiological Dose-Response to Anterior Thalamic Deep Brain Stimulation in Drug-Resistant Focal Epilepsy
Drug Resistant Epilepsy, Focal Epilepsy
Recruiting
Effect of Blue Light on Vagus Nerve Stimulation in Patients With Refractory Epilepsy
Refractory Epilepsy
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
Zhuo Huang, PhD principal investigator
Peking University School of Pharmaceutical Sciences
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 Sirolimus in people with Epilepsy, 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 8 inclusion and 17 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 31 Dec 2024. 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.). The study lists 2 primary outcomes in all. 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 31 Dec 2024.