Effects of Antiepileptic Drugs on Brain Excitability
|First Received Date ICMJE||February 15, 2003|
|Last Updated Date||March 3, 2008|
|Start Date ICMJE||February 2003|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00054990 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Effects of Antiepileptic Drugs on Brain Excitability|
|Official Title ICMJE||The Effects Of Antiepileptic Drugs On Cortical Excitability|
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.
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.
|Study Type ICMJE||Observational|
|Study Design ICMJE||Not Provided|
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Not Provided|
|Study Population||Not Provided|
|Intervention ICMJE||Not Provided|
|Study Groups/Cohorts||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Estimated Completion Date||March 2004|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
Normal volunteers will be male or female, aged 18 to 55 at protocol entry without any of the exclusion criteria described below.
Patients will be excluded from this study if they:
|Ages||Child, Adult, Senior|
|Accepts Healthy Volunteers||Yes|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00054990|
|Other Study ID Numbers ICMJE||030107, 03-N-0107|
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|Plan to Share Data||Not Provided|
|IPD Description||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Institute of Neurological Disorders and Stroke (NINDS)|
|Collaborators ICMJE||Not Provided|
|Investigators ICMJE||Not Provided|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||March 2004|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP