Effects of Antiepileptic Drugs on Brain Excitability

March 3, 2008 updated by: National Institute of Neurological Disorders and Stroke (NINDS)

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.

Study Overview

Status

Completed

Conditions

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.

Study Type

Observational

Enrollment

40

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institute of Neurological Disorders and Stroke (NINDS)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Neurological Disorders and Stroke (NINDS)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2003

Study Completion

March 1, 2004

Study Registration Dates

First Submitted

February 15, 2003

First Submitted That Met QC Criteria

February 14, 2003

First Posted (Estimate)

February 17, 2003

Study Record Updates

Last Update Posted (Estimate)

March 4, 2008

Last Update Submitted That Met QC Criteria

March 3, 2008

Last Verified

March 1, 2004

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • 030107
  • 03-N-0107

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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