Trial document





This trial has been registered retrospectively.
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  DRKS00000788

Trial Description

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Title

Differential effect of Carbamazepine on cortical excitability in subjects with different genotypes for SCN1A as measured by transcranial magnetic stimulation (TMS)

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Trial Acronym

EPICURE SP 5- TMS- SCN1A

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URL of the Trial

[---]*

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Brief Summary in Lay Language

In the present study the influence of Carbamazepin, a drug against epilepsy, on the excitability on the brain shall be investigated. The patient collective will comprise healthy patients (male and female) older 18 years. Former investigations showed, that Carbamazepin binds at a sodium channnel in the brain, for which there exist different variants, which are defined as AA, AG or GG. Further there exist hints, that patients with genotype GG need lower Carbamazepin dosages than patients with genotype AA. Patients with genotype AG need medium dosages. In the population approximately 25% have genotype AA, 53% genotype AG and 22% genotype GG.
In the present study it shall be investigated, if the effect of Carbamazepin at sodium channels of patients with different genotypes differs. As measuring technique we use the "
transkranielle Magnetstimulation" (TMS).

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Brief Summary in Scientific Language

In the present study it shall be investigated, if the effect of Cabamazepin at voltage-dependent sodium channels, detectable via TMS, differs in healthy patients, depending on the polymorphism for the SCN1 A gene. Further it shall be investigated, if there are differences in the baseline value measurements at the sodium channels for both genotypes. Further more a possible influence of other polimorphisms (rs41307846, c.2392C->T in CACNA1H, rs3751664, rs4906902) which might influence the cortical excitability, shall be investigated.

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Organizational Data

  •   DRKS00000788
  •   2011/04/05
  •   [---]*
  •   yes
  •   Approved
  •   02/09(A), Ethik-Kommission des Fachbereichs Medizin der Philipps-Universität Marburg
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Secondary IDs

  •   2008-003392-40 
  •   4034948 
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Health Condition or Problem studied

  •   G40 -  Epilepsy
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Interventions/Observational Groups

  •   400mg Carbamazepine (CBZ)
    1.Product: (Tegretal®)

    Dosing schedule:
    unique oral administration of 400 mg Carbamazepine (Tegretal®) with a washout phase of at least 2 weeks
    Mode of administration:
    Oral application
  •  
    2.Product : Placebo
    Dosing schedule:
    Unique administration of placebo with a washout phase of at least 2 weeks
    Mode of administration:
    Oral application
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Characteristics

  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Blinded
  •   patient/subject
  •   Placebo
  •   Pharmacogenetics
  •   Crossover
  •   II
  •   N/A
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Primary Outcome

The primary endpoint of the study is the difference (RMTcarbamazepine-RMTbaseline,c)-(RMTplacebo-RMTbaseline,p) ( RMT=RESTING MOTOR THRESHOLD).
Measurement technique: transcranial magnetstimulation (TMS)
Timepoint of measurement:each time before intake of medikation (Carbamazepin or Placebo) and approx.5,5h after intake of medication(Carbamazepin or Placebo)

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Secondary Outcome

- Mean of the baseline RMT-values (Resting Motor Threshhold) in one healthy patient
- Change of the TMS (Transcraniale Magnetstimulations)-Parameter CSP(CORTICAL SILENT PERIOD), ICI (INTERVAL INTRACORTICAL INHIBITION) and ICF (INTRACORTICAL FACILITATION)
- Change of the TMS Parameter RMT, CSP, ICI and ICF in patients with different genotypes of polymorphisms rs41307846, c.2392C->T in CACNA1H, rs3751664, rs4906902
- Timepoint of measurement:each time before intake of medikation (Carbamazepin or Placebo) and approx.5,5h after intake of medication(Carbamazepin or Placebo)
- Measurement technique: transcranial magnetstimulation

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
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Recruitment

  •   Actual
  •   2009/09/16
  •   106
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

• Men and women age ≥18 years
• Righthandedness as investigated by the Edinburgh handedness inventory (EHI ≥80)
• Provided signed written informed consent
• Cognitive and physical ability to understand the experimental procedure, to take the antiepileptic medication and to be investigated by TMS

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Exclusion Criteria

• Progressive neurological disorder
• Admission for a psychiatric disorder within the last 6 months, attempted suicide, psychosis or other severe psychiatric disorder
• Severe disease of the liver, kidneys or heart
acute intermittend porphyria
• Severe endocrinological disorder
• Disturbances of the sodium levels
• Cancer
• Glaucoma
• Pregnancy or lactation period
• Epileptic or non-epileptic seizures
• Chronic alcohol- or drug- abuse within the last two years
• Allergic reaction to the medication tested
• Intake of antiepileptic drugs or other drugs influencing cortical excitability
• Metal implantates in head-neck-area
• Other abnormal laboratory results, medical history or clinical findings that might be of disadvantage for the subject or the study
• Inclusion in another clinical or neurophysiological study at the time of investigation

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Addresses

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    • Philipps-Universität Marburg
    • Biegenstrasse 10
    • 35037   Marburg
    • Germany
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    • Neurologische Klinik der Philipps-Universität Marburg
    • Mr.  Prof Dr  Felix  Rosenow 
    • Baldingerstrasse
    • 35043  Marburg
    • Germany
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    • Neurologische Klinik der Philipps-Universität Marburg
    • Mr.  Prof Dr  Felix  Rosenow 
    • Baldingerstrasse
    • 35043  Marburg
    • Germany
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Sources of Monetary or Material Support

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    • Neurologische Klinik Philipps-Universität Marburg
    • Mr.  PRof.Dr.  Felix  Rosenow 
    • Baldingerstrasse
    • 35043   Marburg
    • Germany
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Status

  •   Recruiting complete, follow-up complete
  •   2011/06/24
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Trial Publications, Results and other Documents

  •   menzler K, Hermsen A, A common SCN1A splice-site polymorphism modifies the effect of carbamazepine on cortical excitability--a pharmacogenetic transcranial magnetic stimulation study, 2014 Feb;55(2):362-9. doi: 10.1111/epi.12515. Epub 2014 Jan 13
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* This entry means the parameter is not applicable or has not been set.