Clinical Trials Logo

Clinical Trial Summary

Background:

Epilepsy is a chronic neurological disease which affects approximately 70,000 patients in Hong Kong and 50 billion people worldwide. Among these patients one-third remained unresponsive to antiepileptic agents. Continual drug manipulation is an essential therapeutic option for these patients with refractory epilepsy. In particular, rational polytherapy has become the mainstay of treatment for the sub-group of patients who have failed two or more antiepileptic drugs (AEDs).

A substantial amount of research has shown that N-methyl-D-aspartate receptors (NMDA) may play a key role in the pathophysiology of several neurological diseases, including epilepsy. Animal models of epilepsy and clinical studies demonstrate that NMDA receptors activity and expression can be altered in association with epilepsy and particularly in some specific seizure types. NMDA receptor antagonists have been shown to have antiepileptic effects in both clinical and preclinical studies. There is some evidence that conventional antiepileptic drugs may also affect NMDA receptor function.

Aims:

To investigate the medium to long-term effects of AMPA/NMDA receptor antagonist in an Asian cohort as there is a relative lack of clinical data in this population To explore the efficacy of AMPA/NMDA receptor antagonist in patients with partial onsets seizures that may secondarily generalize and the specific side effects of AMPA/NMDA receptor antagonist in relation to behavioral problems.

Methods:

A semi-prospective design is adopted to recruit patients who are indicated and started on AMPA/NMDA receptor antagonist aged 12 or above in Hong Kong. This study will collect information about demographic details, medical history and seizure information. Assessment of seizure frequency is based on seizure diary and interviews with family members. Physical examination, electrocardiogram and other medical information relevant to the follow-up of the patient will be collected.


Clinical Trial Description

Epilepsy is a chronic neurological disease which affects approximately 70,000 patients in Hong Kong and 50 billion people worldwide. Among these patients, one-third remained unresponsive to antiepileptic agents. Continual drug manipulation is an essential therapeutic option for these patients with refractory epilepsy. In particular, rational polytherapy has become the mainstay of treatment for the sub-group of patients who have failed two or more antiepileptic drugs (AEDs).

Using AEDs with different mechanisms of action is a strategy adopted by many doctors around the world. In this regard, perampanel (PER) is an agent which is first in its class, with specific antagonistic action on ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) glutamate receptor of post-synaptic neurons. The pharmacokinetics of PER suggested that it has a half-life of approximately 105 hours and the steady-state concentrations that can be reached in 14 days. PER is approximately 95% bound to plasma proteins. This metabolism is mediated by CYP 3A4 or CYP 3A5. The usual dosage of PER is between 2mg and 12 mg. PER can be administered once daily.

A total of five clinical studies demonstrated the efficacy of PER among patients with refractory epilepsy. These were all double-blind studies and all of them evaluated the 50% responder rate as a seizure outcome. The corresponding risk ratio for 50% responder rates for 4mg, 8mg and 12mg were 1.54, 1.8 and 1.72. The most common treatment-emergent adverse effects were dizziness, drowsiness, headache, fatigue, nasopharyngitis. The pooled results suggested that a higher dose was more efficacious if the side effects could be tolerated. There was an on-going study on the use of PER among patients with secondarily generalized seizures. Perampanel has been approved in many countries such as USA, EU, Australia, Canada, Switzerland, Singapore, and Malaysia, as an adjunctive therapy for refractory partial seizures with or without secondary generalisation among patients above 12 years of age.

A substantial amount of research has shown that N-methyl-D-aspartate receptors (NMDA) may play a key role in the pathophysiology of several neurological diseases, including epilepsy. Animal models of epilepsy and clinical studies demonstrate that NMDA receptors activity and expression can be altered in association with epilepsy and particularly in some specific seizure types. NMDA receptor antagonists have been shown to have antiepileptic effects in both clinical and preclinical studies. There is some evidence that conventional antiepileptic drugs may also affect NMDA receptor function. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT03457961
Study type Observational
Source Chinese University of Hong Kong
Contact Sau Man Celia Tse
Phone 85257431802
Email saumanceliatse@cuhk.edu.hk
Status Recruiting
Phase
Start date July 23, 2016
Completion date July 1, 2021

See also
  Status Clinical Trial Phase
Recruiting NCT02245061 - Cortical Excitability Assessment Using Paired Pulses N/A
Terminated NCT05081518 - A Study of Lu AG06466 in Participants With Treatment Resistant Focal Epilepsy Phase 1
Withdrawn NCT05481905 - ENACT: A Study of ENX-101 as Adjunctive Treatment in Patients With Focal Seizures Phase 2
Completed NCT02208492 - The Effects on Cognitive Function of Levetiracetam (Keppra®) Compared to Carbamazepine (Tegretol®, Carmazepine®) as Monotherapy for Children With Partial Seizure; A Multicentric Randomized Controlled Study Phase 4
Recruiting NCT04839601 - RNS System RESPONSE Study N/A
Completed NCT02898935 - Improvement of the Accuracy of Spatial Representation of Invasive Exploratory Electrodes in Focal Epilepsy
Enrolling by invitation NCT05748236 - The Efficacy and Safety of Lamotrigine Versus Carbamazepine in Focal Epilepsy Phase 4
Terminated NCT01724918 - Lacosamide IV and EEG/EKG (LIVE) Study Phase 2
Completed NCT00855738 - A Prospective, Observational Study On The Effectiveness Of New Antiepileptic Drugs As First Bitherapy In The Daily Clinical Practice Phase 4
Recruiting NCT06309966 - Study to Determine if BHV-7000 is Effective and Safe in Adults With Refractory Focal Onset Epilepsy Phase 2/Phase 3
Not yet recruiting NCT06210022 - Cognitive Impairment in Drug-resistant and Drug-responsive Focal Cryptogenic Epilepsy
Completed NCT01311440 - Modified Atkins Diet Treatment for Adults With Drug-resistant Epilepsy N/A
Terminated NCT03955432 - Long-term Cardiac Monitoring in Epilepsy N/A
Recruiting NCT06132893 - A Study to Determine if BHV-7000 is Effective and Safe in Adults With Refractory Focal Onset Epilepsy Phase 2/Phase 3
Recruiting NCT05100771 - Optimized Volumetry in Radiology: Interest in Pediatric Brain MRI in the Exploration of Focal Epilepsy
Recruiting NCT04879433 - Prospective Open-label Evaluation of Cenobamate Adjunctive Treatment of Adults With Refractory Focal Epilepsy
Active, not recruiting NCT03916848 - Novel Network Analysis of Intracranial Stereoelectroencephalography N/A
Recruiting NCT05198882 - Clinical Evaluation of Interstitial Laser Thermal Therapy Under Continuous MRI Monitoring as a Minimally Invasive Treatment of Patients With Medically Unbalanced Partial Epilepsy Phase 1
Recruiting NCT05981755 - Breathing Rescue for SUDEP Prevention N/A
Not yet recruiting NCT06443463 - Long-term Safety and Tolerability of BHV-7000 Phase 2