Effects of Lacosamide on Human Motor Cortex Excitability: a Transcranial Magnetic Stimulation Study

Not Applicable

Completed

• Conditions: Healthy Male Volunteers
• Interventions: Drug: Placebo; Drug: Carbamazepine; Drug: Lacosamide

• Registration Number: NCT01382017
• Lead Sponsor: University of Kiel

Brief Summary

This study has been designed to explore dose-depended effects of lacosamide (LCM) on motor cortex excitability with TMS in a randomized, double-blind, placebo-controlled crossover trial in young healthy human subjects, and to compare the pattern of excitability changes induced by LCM with those of carbamazepine (CBZ). LCM selectively enhances slow inactivation of voltage-gated sodium channel, and, in contrast to CBZ, does not affect steady-state fast inactivation (Errington et al., 2006). The enhancement of slow inactivation of sodium channels by LCM is a novel manner to modulate sodium channels and leads to normalization of activation thresholds and a reduced pathophysiological hyper-responsiveness, thereby effectively controlling neuronal hyperexcitability without affecting physiological activity (Beyreuther et al., 2007). Therefore, it is thought that LCM, compared to CBZ, will be better tolerated in clinical settings while being as or even more effective in controlling seizure activity. On the basis of the results from nonhuman studies, it is hypothesized that the TMS profile of LCM will be distinguishable from that of CBZ. CBZ, like other 'classical' sodium channel blockers such as phenytoin, predominantly demonstrated elevated TMS motor thresholds indicating reduced neuronal membrane excitability, without developing significant changes of synaptic intracortical inhibition and facilitation (Ziemann et al., 1996; Chen et al., 1997; Lee et al., 2005). Because of its novel mode of action it can only be speculated which TMS parameters LCM might affect. For example, more than exclusively affecting neuronal membrane excitability, LCM could possibly also affect inhibitory mechanisms such as short- and long-latency intracortical inhibition (Valls-Sole et al., 1992; Kujirai et al., 1993). This would in line with other well-tolerated modern antiepileptic drugs (Ziemann et al., 1996; Reis et al., 2002; Lang et al., 2006).

Detailed Description

Not available

Study Timeline

• Study Start: 2011-06
• Study First Submitted: 2011-06-23
• Study First Submitted QC: 2011-06-24
• Study First Posted: 2011-06-27
• Status Verified: 2012-08
• Primary Completion: 2012-08
• Study Completion: 2012-08
• Last Update Submitted: 2012-08-28
• Last Update Posted: 2012-08-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 18

Inclusion Criteria

• healthy
• male
• right-handed
• aged 18-45 years

Exclusion Criteria

• cardiac pacemaker
• metal implants in the head
• intake of any medication
• previous neurologic, psychiatric, or chronic internal diseases
• pregnancy or breastfeeding; drug, nicotine, or alcohol abuse
• known or expected intolerance to soy beans, peanuts, LCM or CBZ; abnormal ECG with prolonged PQ-interval
• participation in another clinical trial within the previous 8 weeks

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo arm
Carbamazepine 600	Carbamazepine	Carbamazepine 600 mg
Lacosamide 400	Lacosamide	Lacosamide 400 mg
Lasosamide 200	Lacosamide	Lacosamide 200 mg

Primary Outcome Measures

Name	Time	Method
TMS measures of cortical excitability	within 24h after intake of study medication	Transcranial magnetic stimulation (TMS) measurements included resting motor thresholds (RMT) and active motor thresholds (AMT), the intensity to evoke MEP of ∼1mV peak-to-peak amplitude (SI1mV), short-interval intracortical inhibition/intracortical facilitation (SICI/ICF), long-interval intracortical inhibition (LICI), short-interval intracortical facilitation (SICF), recruitment curves, MEP under tonic activation (aMEP), and cortical silent period (CSP), and MEP changes in response to short trains of repetitive TMS.

Trial Locations

Locations (1)

Departmenr of Neurology, UKSH Campus Kiel; 🇩🇪 Kiel, Germany