Propranolol Adjuvant Treatment of Focal Refractory Epilepsy (PATFRE)

NCT06719804 | Not Yet Recruiting Early Phase 1

• 1 other identifier: 2024-260-002
• Study Type: interventional
• Target: 15
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Epilepsy, Drug Resistant

Keywords

Propranolol; Focal Refractory Epilepsy; CAMP-PKA-MEK/ERK pathway; non-selective beta-adrenergic antagonists

Outcome Measures

Primary Outcomes (2)

• 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

  assessed per 28 days during the treatment.

• Seizure Responder Rate

  The proportion of patients with a ≥ 50% reduction from Baseline in seizure frequency.

  short-term treatment period (ending at 3 months); long-term follow-up period (ending at 12 months).

Secondary Outcomes (3)

• Seizure Severity

  Baseline observation period; short-term treatment period (ending at 3 months); long-term follow-up period (ending at 12 months).

• Life quality evaluation

  Baseline observation period; short-term treatment period (ending at 3 months); long-term follow-up period (ending at 12 months).

• Adverse Events

  through study completion, 12 months.

Study Arms (1)

Open label single arm, drug propanolol

EXPERIMENTAL

All subjects will receive the experimental drug

Drug: Propranolol

Interventions

Propranolol DRUG

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.

Open label single arm, drug propanolol

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• 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.

Sponsors & Collaborators

• Xuanwu Hospital, Beijing: lead
• Peking University: collaborator

MeSH Terms

Conditions

Drug Resistant Epilepsy

Interventions

Propranolol

Condition Hierarchy (Ancestors)

Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• Liankun Ren, MD

  Xuanwu Hospital, Beijing

  PRINCIPAL INVESTIGATOR

• Zhuo Huang, PhD

  Peking University School of Pharmaceutical Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Liankun Ren, MD

CONTACT

+86 13681576621; renlk2022@outlook.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 1, 2024
• First Posted: December 6, 2024
• Study Start: December 5, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: December 10, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share