NCT06719804

Propranolol Adjuvant Treatment of Focal Refractory Epilepsy (PATFRE)

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

• Status: Not Yet Recruiting
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 15 (estimated)
• Sponsor: Xuanwu Hospital, Beijing · Academic / Other
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Not accepted

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 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.

Conditions

• Epilepsy, Drug Resistant

Interventions

Type	Name	Description
DRUG	Propranolol	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.

Timeline

• Start date: 2024-12-05
• Primary completion: 2027-12-01
• Completion: 2028-12-01
• First posted: 2024-12-06
• Last updated: 2024-12-10