Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01823159
Recruitment Status : Completed
First Posted : April 4, 2013
Last Update Posted : December 2, 2014
Sponsor:
Collaborators:
GlaxoSmithKline
Université Catholique de Louvain
Information provided by (Responsible Party):
Michel Ossemann, 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.

Condition or disease Intervention/treatment Phase
Epilepsy Drug: retigabine Drug: placebo Phase 3

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Cortical Excitability Changes Induced by Retigabine: a Transcranial Magnetic Stimulation Study
Study Start Date : April 2013
Actual Primary Completion Date : December 2013
Actual Study Completion Date : January 2014

Resource links provided by the National Library of Medicine

Drug Information available for: Ezogabine

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 Name: 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




Primary Outcome Measures :
  1. Measurement of TMS cortical excitability parameter before and after drug intake [ Time Frame: 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 :
  1. Assessing tolerability of a single dose intake of retigabine [ Time Frame: 24 hours after drug intake ]
    Reporting of eventual side effect after the intake of retigabine vs placebo with a structurate questionnaire.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01823159


Locations
Layout table for location information
Belgium
CHU Mont-Godinne
Yvoir, Namur, Belgium, 5350
Sponsors and Collaborators
University Hospital of Mont-Godinne
GlaxoSmithKline
Université Catholique de Louvain
Investigators
Layout table for investigator information
Principal Investigator: Michel Ossemann, MD CHU Mont-Godinne

Layout table for additonal information
Responsible Party: Michel Ossemann, Principal Investigator, University Hospital of Mont-Godinne
ClinicalTrials.gov Identifier: NCT01823159     History of Changes
Other Study ID Numbers: CERETI
2012-003809-98 ( EudraCT Number )
First Posted: April 4, 2013    Key Record Dates
Last Update Posted: December 2, 2014
Last Verified: December 2014
Keywords provided by Michel Ossemann, University Hospital of Mont-Godinne:
retigabine
cortical excitability
Transcranial Magnetic Stimulation
Additional relevant MeSH terms:
Layout table for MeSH terms
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Ezogabine
Anticonvulsants
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action