Effects of Antiepileptic Drugs on Brain Excitability
Information source: National Institutes of Health Clinical Center (CC)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Healthy
Phase: N/A
Status: Completed
Sponsored by: National Institute of Neurological Disorders and Stroke (NINDS)
Summary
This study will evaluate the usefulness of transcranial magnetic stimulation (TMS) in
measuring cortical excitability. The cortex is the outer part of the brain. Patients with
seizures have increased cortical excitability and are often treated with antiepileptic drugs
to reduce this excitability. The therapeutic effects of antiepileptic drugs are usually
tracked with blood tests that measure their blood levels. However, these blood tests may not
always correctly reflect the effects of the drugs on the brain.
TMS has been used successfully to measure cortical excitability in many neurological
diseases, including epilepsy, and may be helpful in measuring drug effects on the brain
directly. For this procedure, a wire coil is held over the scalp. A brief electrical
current is passed through the coil, creating a magnetic pulse that stimulates the brain.
This may cause a pulling sensation on the skin under the coil and twitching in muscles of the
face, arm, or leg. During the stimulation, the participant may be asked to tense certain
muscles slightly or perform other simple actions.
Healthy normal volunteers between 18 and 55 years of age may be eligible for this study.
Candidates will be screened with a medical history, physical and neurological examination,
electroencephalogram (EEG), and blood tests.
On the first day of the study, participants will have a baseline TMS and will be randomly
assigned to take one of two antiepileptic drugs: group A will take the carbamazepine; group B
will take lamotrigine. If they wish, participants may be admitted to the NIH Clinical Center
for the first 5 days of drug administration while the proper dosage is being determined.
They will then be discharged and continue taking the drug for a total of 36 days. During
this time, they will have daily blood tests and TMS from days 2 through 5, and again on days
12 and 36. Group A will have additional blood sampling and TMS on days 37, 39, 44, and 53;
Group B will have blood tests and TMS on days 38, 40, 45, and 53.
Clinical Details
Official title: The Effects Of Antiepileptic Drugs On Cortical Excitability
Study design: N/A
Detailed description:
Objectives. Epilepsy is a condition characterized by abnormally increased cortical
excitability, and antiepileptic drugs (AEDs) control epilepsy by reducing cortical
excitability. Serum blood levels presently represent the standard measure utilized to track
the therapeutic effects of AEDs. However, peripheral blood levels do not always reflect
brain levels, or provide direct information on cortical excitability. Transcranial magnetic
stimulation (TMS) is a non-invasive technique that allows accurate measures of this
parameter. The purpose of this protocol is to test the hypothesis that TMS measures of
cortical excitability will correlate with serum blood levels of AEDs, and reflect clinical
effects on cortical function directly in healthy volunteers. This information is crucial to
reach the ultimate goal of developing a reliable quantitative measurement of central
physiological effects of AEDs in epileptic patients.
Study Population. 40 normal volunteers aged 18 to 55 years will be recruited for this
study.
Design. Subjects will be assigned to either of two groups, with each group receiving one of
the following drugs; carbamazepine (CBZ), and lamotrigine (LTG). Measures of cortical
excitability will be performed using TMS in various drug treatment phases: at baseline
(before drug intake); during the AED induction period (once a day for the first 5 days),
after 12 days of drug intake at the maximum dose during steady state; and 3, 7, and 14
half-lives after, and finally three weeks after abrupt drug withdrawal. Blood sampling for
drug levels will be performed at each TMS study.
Outcome Measures. The primary outcome variables will be MEP size, measured from recruitment
curves. MEP size difference from baseline will be compared to the serum drug level for each
drug.
Eligibility
Minimum age: N/A.
Maximum age: N/A.
Gender(s): Both.
Criteria:
INCLUSION CRITERIA:
Normal volunteers will be male or female, aged 18 to 55 at protocol entry without any of
the exclusion criteria described below.
EXCLUSION CRITERIA:
Patients will be excluded from this study if they:
1. are pregnant (tested with urine pregnancy test).
2. have severe coronary disease.
3. have metal anywhere in the cranium except the mouth.
4. have intracardiac lines.
5. have increased intracranial pressure as expressed by the presence of papilledema.
6. have cardiac pacemakers.
7. take neuroleptic or antidepressant medications.
8. any neurologic disease including epilepsy.
9. taking any psychiatric drugs.
10. any other documented systemic illness.
11. history of drug allergy.
Locations and Contacts
National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, Maryland 20892, United States
Additional Information
Related publications: Burstein AH, Horton RL, Dunn T, Alfaro RM, Piscitelli SC, Theodore W. Lack of effect of St John's Wort on carbamazepine pharmacokinetics in healthy volunteers. Clin Pharmacol Ther. 2000 Dec;68(6):605-12. Cantello R, Civardi C, Cavalli A, Varrasi C, Tarletti R, Monaco F, Migliaretti G. Cortical excitability in cryptogenic localization-related epilepsy: interictal transcranial magnetic stimulation studies. Epilepsia. 2000 Jun;41(6):694-704. Chen R, Samii A, Canos M, Wassermann EM, Hallett M. Effects of phenytoin on cortical excitability in humans. Neurology. 1997 Sep;49(3):881-3.
Starting date: February 2003
Ending date: March 2004
Last updated: March 3, 2008
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