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

Healthy Male Volunteers Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01382017
• Other study ID #: LCM-TMS-2010
• Status: Completed
• Phase: N/A
• First received: June 23, 2011
• Last updated: August 28, 2012
• Start date: June 2011
• Est. completion date: August 2012

Study information

• Verified date: August 2012
• Source: University of Kiel
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medicinal Devices (BfArM)
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: August 2012
• Est. primary completion date: August 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Healthy Male Volunteers

Intervention

Drug:
• Lacosamide
Lacosamide 200 or 400 mg
• Placebo
Placebo
• Carbamazepine
Carbamazepine 600 mg

Locations

Country	Name	City	State
Germany	Departmenr of Neurology, UKSH Campus Kiel	Kiel

Sponsors (2)

Lead Sponsor	Collaborator
University of Kiel	UCB Pharma

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	TMS measures of cortical excitability	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.	within 24h after intake of study medication	No

External Links

•   Department of Neurology, University of Kiel, Germany