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

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.

Study Overview

• Status: Completed
• Conditions: Epilepsy
• Intervention / Treatment: Drug: retigabine; Drug: placebo

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 Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Namur
    • Yvoir, Namur, Belgium, 5350
      • CHU Mont-Godinne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Retigabine; Administration of a single dose of 400 mg retigabine, two hours before the measures	Drug: retigabine; Single oral administration of a 400 mg tablet.; Other Names: ezogabine
PLACEBO_COMPARATOR: placebo; Randomized administration of a single dose of placebo, two hours before the measures.	Drug: placebo; Single oral administration of a tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of TMS cortical excitability parameter before and after drug 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.	Two hours after oral intake

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University Hospital of Mont-Godinne
• Collaborators: GlaxoSmithKline; Université Catholique de Louvain
• Investigators: Principal Investigator: Michel Ossemann, MD, CHU Mont-Godinne

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (ACTUAL): December 1, 2013
• Study Completion (ACTUAL): January 1, 2014

Study Registration Dates

• First Submitted: March 24, 2013
• First Submitted That Met QC Criteria: April 2, 2013
• First Posted (ESTIMATE): April 4, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): December 2, 2014
• Last Update Submitted That Met QC Criteria: December 1, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: Transcranial Magnetic Stimulation; cortical excitability; retigabine
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Anticonvulsants; Ezogabine
• Other Study ID Numbers: CERETI; 2012-003809-98 (EUDRACT_NUMBER)