Epilepsy
Conditions
Keywords
retigabine, cortical excitability, Transcranial Magnetic Stimulation
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.
Interventions
DRUGretigabine
Single oral administration of a 400 mg tablet.
DRUGplacebo
Single oral administration of a tablet
Sponsors
GlaxoSmithKline
Université Catholique de Louvain
University Hospital of Mont-Godinne
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Belgium
Outcome results
None listed