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

Epilepsy Clinical Trial

— CERETI  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01823159
• Other study ID #: CERETI
• Secondary ID: 2012-003809-98
• Status: Completed
• Phase: Phase 3
• First received: March 24, 2013
• Last updated: December 1, 2014
• Start date: April 2013
• Est. completion date: January 2014

Study information

• Verified date: December 2014
• Source: University Hospital of Mont-Godinne
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health Products
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: January 2014
• Est. primary completion date: December 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

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

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Epilepsy

Intervention

Drug:
• retigabine
Single oral administration of a 400 mg tablet.
• placebo
Single oral administration of a tablet

Locations

Country	Name	City	State
Belgium	CHU Mont-Godinne	Yvoir	Namur

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital of Mont-Godinne	GlaxoSmithKline, Université Catholique de Louvain

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	Yes