Epilepsy, Drug ResistantEarly Phase 1NCT06719804
Propranolol Adjuvant Treatment of Focal Refractory Epilepsy (PATFRE)
A Early Phase 1 study testing Propranolol in people with Epilepsy, Drug Resistant, run by Xuanwu Hospital, Beijing.
Trial summary
The aim of this study is to evaluate the clinical efficacy of propranolol as an adjunctive treatment for refractory epilepsy. The significance of this research lies in exploring whether propranolol, as an inhibitor of the CAMP-PKA-MEK/ERK pathway, can provide anticonvulsant effects for a wider range of refractory… 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?
- Propranolol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- No sites listed yet
- Study dates
- 5 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 propranolol, 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.
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- Free of major medical illnesses including:
- Cardiac diseases (history of cardiac valve disease, coronary artery disease, congestive heart failure, A-V block, peripheral vascular disease, any cardiac arrhythmia/bradycardia)
- Histories of asthma, bronchospastic disease, or obstructive pulmonary disease
- Severe allergic reactions to medications which are included in the beta blocker family
- Currently treated with a beta adrenergic receptor antagonist or Previously used within 12 months
- Uncontrolled Diabetes (HbA1c of ≤ 8 if previously tested)
- Uncontrolled hypotension
- Immunodeficiency disorders, liver or kidney diseases, acute infections, or advanced-stage tumors.
- 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.
- 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
No sites are listed yet. 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 Propranolol as an Adjunctive Treatment for Focal Refractory Epilepsy: A Pilot Study
The aim of this study is to evaluate the clinical efficacy of propranolol as an adjunctive treatment for refractory epilepsy. The significance of this research lies in exploring whether propranolol, as an inhibitor of the CAMP-PKA-MEK/ERK pathway, can provide anticonvulsant effects for a wider range of refractory epilepsy patients. The study holds the potential to offer a novel adjunctive anticonvulsant treatment strategy targeting the CAMP-PKA-MEK/ERK pathway, specifically administered for seizure events, and applicable to various forms of refractory epilepsy.
Read the detailed description
Propranolol is a non-selective β-adrenergic receptor antagonist that blocks β1 and β2 adrenergic receptors, antagonizing sympathetic nervous stimulation and catecholamine effects. It is widely used in the treatment of various cardiovascular diseases. Additionally, propranolol can intervene in the reconsolidation process of pathological memories and is used to treat neuropsychiatric disorders such as post-traumatic stress disorder (PTSD) and drug addiction. Professor Huang Zhuo's team, using a conditioned epilepsy memory mouse model, administered propranolol during the "epilepsy memory" reconsolidation window (within 5 minutes) to inhibit the ERK pathway, significantly reducing subsequent seizure episodes induced by sensory stimuli. However, intervention outside the reconsolidation window (9 hours later) had no significant effect. This study, however, only verified the alleviating effect of propranolol treatment on subsequent seizures in an animal model, and its clinical efficacy in controlling epilepsy still needs further validation.
Based on the "epilepsy memory" mechanism, propranolol combined with memory recall reconsolidation paradigms is expected to become an effective adjunctive treatment for refractory epilepsy. Evaluating its efficacy and safety not only helps determine its therapeutic value in epilepsy treatment but also provides important guidance for clinical practice, playing a crucial role in the translation from basic research to clinical application.
Current small-sample animal studies have confirmed that administering propranolol within the "epilepsy memory" reconsolidation window can reduce the frequency of seizures and shorten the duration of seizures in epileptic mice. However, there is no large-scale clinical study validating the impact of propranolol on clinical seizures in patients. This study is a prospective, single-arm open-label trial aimed at preliminarily exploring the efficacy and safety of propranolol in the treatment of refractory epilepsy. The primary outcome measures are the proportion of patients with a ≥50% reduction in the frequency of refractory epilepsy seizures and a ≥50% reduction in epileptiform discharges on vEEG monitoring compared to baseline. Secondary outcomes include the severity of seizures (measured by the Liverpool Epilepsy Severity Scale) and the patient's quality of life (measured by the QOLIE-31-P scale). Adverse events during propranolol treatment will also be recorded, providing an objective assessment of the side effects and complications of propranolol in the treatment of epilepsy.
- Conditions
- Epilepsy, Drug Resistant
- Being tested
- Propranolol
- Keywords
- Propranolol, Focal Refractory Epilepsy, CAMP-PKA-MEK/ERK pathway, non-selective beta-adrenergic antagonists
- 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.
PropranololDrug
Oral administration is given solely for the epilepsy seizure event. Dosage: 20mg per dose; The patient's blood pressure and heart rate are monitored after the seizure; if the SBP is above 90 mmHg and the heart rate is above 60 beats per minute, then patients are instructed to take propranolol within 1 hour of a seizure . If the seizure frequency is excessively high, the interval between doses should be no less than 6 hours and the medication should not be administered more than 3 times a day.
| Study group | Role | What they receive |
|---|---|---|
| Open label single arm, drug propanolol | Experimental | All subjects will receive the experimental drug Receives: Drug: Propranolol |
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.
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 start5 Dec 2024 (estimated)
- 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
- NCT06719804
- Sponsor's protocol ID
- 2024-260-002
- Status last verified
- Dec 2024
- First submitted
- 1 Dec 2024
- Last updated
- 10 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- 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 10 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Safety and Efficacy Evaluation of Propranolol as an Adjunctive Treatment for Focal Refractory Epilepsy: A Pilot Study
- ClinicalTrials.gov ID
- NCT06719804
- Acronym / sponsor ID
- 2024-260-002
- Conditions
- Epilepsy, Drug Resistant
- Keywords
- Propranolol, Focal Refractory Epilepsy, CAMP-PKA-MEK/ERK pathway, non-selective beta-adrenergic antagonists
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Xuanwu Hospital, BeijingUniversity, hospital or other
- Collaborators
- Peking University
- Study start
- 5 Dec 2024 (estimated)
- 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 propranolol as an adjunctive treatment for refractory epilepsy. The significance of this research lies in exploring whether propranolol, as an inhibitor of the CAMP-PKA-MEK/ERK pathway, can provide anticonvulsant effects for a wider range of refractory epilepsy patients. The study holds the potential to offer a novel adjunctive anticonvulsant treatment strategy targeting the CAMP-PKA-MEK/ERK pathway, specifically administered for seizure events, and applicable to various forms of refractory epilepsy.
Detailed description
Propranolol is a non-selective β-adrenergic receptor antagonist that blocks β1 and β2 adrenergic receptors, antagonizing sympathetic nervous stimulation and catecholamine effects. It is widely used in the treatment of various cardiovascular diseases. Additionally, propranolol can intervene in the reconsolidation process of pathological memories and is used to treat neuropsychiatric disorders such as post-traumatic stress disorder (PTSD) and drug addiction. Professor Huang Zhuo's team, using a conditioned epilepsy memory mouse model, administered propranolol during the "epilepsy memory" reconsolidation window (within 5 minutes) to inhibit the ERK pathway, significantly reducing subsequent seizure episodes induced by sensory stimuli. However, intervention outside the reconsolidation window (9 hours later) had no significant effect. This study, however, only verified the alleviating effect of propranolol treatment on subsequent seizures in an animal model, and its clinical efficacy in controlling epilepsy still needs further validation.
Based on the "epilepsy memory" mechanism, propranolol combined with memory recall reconsolidation paradigms is expected to become an effective adjunctive treatment for refractory epilepsy. Evaluating its efficacy and safety not only helps determine its therapeutic value in epilepsy treatment but also provides important guidance for clinical practice, playing a crucial role in the translation from basic research to clinical application.
Current small-sample animal studies have confirmed that administering propranolol within the "epilepsy memory" reconsolidation window can reduce the frequency of seizures and shorten the duration of seizures in epileptic mice. However, there is no large-scale clinical study validating the impact of propranolol on clinical seizures in patients. This study is a prospective, single-arm open-label trial aimed at preliminarily exploring the efficacy and safety of propranolol in the treatment of refractory epilepsy. The primary outcome measures are the proportion of patients with a ≥50% reduction in the frequency of refractory epilepsy seizures and a ≥50% reduction in epileptiform discharges on vEEG monitoring compared to baseline. Secondary outcomes include the severity of seizures (measured by the Liverpool Epilepsy Severity Scale) and the patient's quality of life (measured by the QOLIE-31-P scale). Adverse events during propranolol treatment will also be recorded, providing an objective assessment of the side effects and complications of propranolol in the treatment of epilepsy.
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 propanolol | Experimental | Drug: PropranololAll 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 propranolol, 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 (20 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 |
|---|---|---|
| PropranololOral administration is given solely for the epilepsy seizure event. Dosage: 20mg per dose; The patient's blood pressure and heart rate are monitored after the seizure; if the SBP is above 90 mmHg and the heart rate is above 60 beats per minute, then patients are instructed to take propranolol within 1 hour of a seizure . If the seizure frequency is excessively high, the interval between doses should be no less than 6 hours and the medication should not be administered more than 3 times a day. | Drug | Open label single arm, drug propanolol |
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
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 10 Dec 2024.
- 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
Zhuo Huang, PhD principal investigator
Peking University School of Pharmaceutical Sciences
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Propranolol in people with Epilepsy, Drug Resistant, run by Xuanwu Hospital, Beijing.
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 20 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: opening soon, as of the sponsor's last update on 10 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
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 10 Dec 2024.