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

NCT01382017 | Completed DMC

• 1 other identifier: LCM-TMS-2010
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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).

Conditions

Healthy Male Volunteers

Keywords

lacosamide; carbamazepine; placebo; transcranial magnetic stimulation; TMS; motor cortex; sodium channel; inhibition; threshold

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Placebo arm

Drug: Placebo

Lasosamide 200

EXPERIMENTAL

Lacosamide 200 mg

Drug: Lacosamide

Lacosamide 400

EXPERIMENTAL

Lacosamide 400 mg

Drug: Lacosamide

Carbamazepine 600

ACTIVE COMPARATOR

Carbamazepine 600 mg

Drug: Carbamazepine

Interventions

Lacosamide DRUG

Lacosamide 200 or 400 mg

Lacosamide 400; Lasosamide 200

Placebo DRUG

Placebo

Placebo

Carbamazepine DRUG

Carbamazepine 600 mg

Carbamazepine 600

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Kiel: lead
• UCB Pharma: collaborator

Study Sites (1)

Departmenr of Neurology, UKSH Campus Kiel

Kiel, 24105, Germany

Location

Related Links

• Department of Neurology, University of Kiel, Germany

MeSH Terms

Conditions

Inhibition, Psychological

Interventions

Lacosamide; Carbamazepine

Condition Hierarchy (Ancestors)

Behavior

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Nicolas Lang, PD Dr. med.

  Christian-Albrechts University Kiel, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PD Dr. med.

Study Record Dates

• First Submitted: June 23, 2011
• First Posted: June 27, 2011
• Study Start: June 1, 2011
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: August 29, 2012

Record last verified: 2012-08

Locations

DE (1)