Cortical Excitability Changes Induced by Retigabine: a Transcranial Magnetic Stimulation Study

Phase 3

Completed

• Conditions: Epilepsy
• Interventions: Drug: retigabine; Drug: placebo

• Registration Number: NCT01823159
• Lead Sponsor: University Hospital of Mont-Godinne

Brief Summary

The objective of this study is to characterize the effects of a single-dose of retigabine on cortical excitability in healthy subjects, as quantified by means of TMS.

Detailed Description

Epilepsy is a disorder of brain excitability. Antiepileptic drugs (AEDs) modulate this excitability and transcranial magnetic stimulation (TMS) imposed itself as one of the best noninvasive methods to study cortical excitability in human subjects.

Based on several recent studies, we hypothesize that measuring TMS parameters in the patients suffering from epilepsy can rapidly predict the effectiveness of the newly given AED and, ultimately, guide the optimization of the AED therapy. Characterizing the neurophysiological properties of innovative AEDs such as retigabine with TMS will allow 1) to better understand how AEDs modulate, in vivo, cortical excitability in humans in relation to their mode of action and 2) to establish TMS as a tool for assessing individual responsiveness to a particular AED treatment and for antiepileptic treatment monitoring.

The effects of most AEDs on cortical excitability have been investigated. The modifications of the excitability parameters are related to the specific mode of action of each AED. For the new AED retigabine, at least two modes of action are known: 1) increase in cellular potassium efflux by changing conformation of the KV7.2-7.3 channels and 2) enhancement of GABA-A activity.

Study Timeline

• Study First Submitted: 2013-03-24
• Study Start: 2013-04
• Study First Submitted QC: 2013-04-02
• Study First Posted: 2013-04-04
• Primary Completion: 2013-12
• Study Completion: 2014-01
• Status Verified: 2014-12
• Last Update Submitted: 2014-12-01
• Last Update Posted: 2014-12-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

• age 18-50 years
• being "healthy"
• willing to participate and able to understand study and provide informed consent

Exclusion Criteria

• intake of psycho-active drugs (AEDS, antidepressants, benzodiazepines, neuroleptics, hypnotics, ...)
• alcohol or drug abuse
• antecedent of seizure
• contra-indication to TMS (metal in the head, skull fracture)
• contra-indication to retigabine.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Retigabine	retigabine	Administration of a single dose of 400 mg retigabine, two hours before the measures
placebo	placebo	Randomized administration of a single dose of placebo, two hours before the measures.

Primary Outcome Measures

Name	Time	Method
Measurement of TMS cortical excitability parameter before and after drug intake	Two hours after oral intake	The primary endpoint is the impact of retigabine on TMS cortical excitability parameters in healthy volunteers compared to placebo, in a double-blind cross-over design. These parameters were specifically chosen according to the known dual mechanism of action of retigabine. Modulation of GABA-A receptors and increase of potassium efflux.; The parameters studied are the motor threshold (MT), the amplitude of motor evoked potential (MEP), the cortical silent period (CSP), the short interval intracortical inhibition (SICI), the long interval intracortical inhibition (LICI), the intracortical facilitation (ICF) and the short interval cortical facilitation (SICF).; Parameters are registered before and after retigabine or placebo intake. Modifications of these parameters are recorded and compared for retigabine vs placebo for each subject. A group analysis retigabine vs placebo is also performed.

Secondary Outcome Measures

Name	Time	Method
Assessing tolerability of a single dose intake of retigabine	24 hours after drug intake	Reporting of eventual side effect after the intake of retigabine vs placebo with a structurate questionnaire.

Trial Locations

Locations (1)

CHU Mont-Godinne; 🇧🇪 Yvoir, Namur, Belgium