HealthyNCT00054990
Effects of Antiepileptic Drugs on Brain Excitability
An observational study of Healthy, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Healthy
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2003to Mar 2004
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Normal volunteers will be male or female, aged 18 to 55 at protocol entry without any of the exclusion criteria described below.
Who cannot join
- Patients will be excluded from this study if they:
- are pregnant (tested with urine pregnancy test).
- have severe coronary disease.
- have metal anywhere in the cranium except the mouth.
- have intracardiac lines.
- have increased intracranial pressure as expressed by the presence of papilledema.
Show all 12Show fewer
- have cardiac pacemakers.
- take neuroleptic or antidepressant medications.
- any neurologic disease including epilepsy.
- taking any psychiatric drugs.
- any other documented systemic illness.
- history of drug allergy.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Neurological Disorders and Stroke (NINDS)
Bethesda, Maryland, 20892
About this study
Official title: 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.
Read more
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.
Read the 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.
- Conditions
- Healthy
- Keywords
- Antiepileptic Drugs, Cortical Excitability, Transcranial Magnetic Stimulation, Epilepsy, TMS, Healthy Volunteer, HV
- Medical subject headings
- Epilepsy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2003 (estimated)
- Study startFeb 2003
- Study completionMar 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Enrolment
- 40 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00054990
- Sponsor's protocol ID
- 030107
- Other IDs
- 03-N-0107
- Status last verified
- Mar 2004
- First submitted
- 15 Feb 2003
- Last updated
- 4 Mar 2008
- Results posted
- No
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. doi: 10.1067/mcp.2000.111530.
PubMed 11180020Cantello 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. doi: 10.1111/j.1528-1157.2000.tb00230.x.
PubMed 10840401Chen R, Samii A, Canos M, Wassermann EM, Hallett M. Effects of phenytoin on cortical excitability in humans. Neurology. 1997 Sep;49(3):881-3. doi: 10.1212/wnl.49.3.881.
PubMed 9305361
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects Of Antiepileptic Drugs On Cortical Excitability
- ClinicalTrials.gov ID
- NCT00054990
- Acronym / sponsor ID
- 030107
- Conditions
- Healthy
- Keywords
- Antiepileptic Drugs, Cortical Excitability, Transcranial Magnetic Stimulation, Epilepsy, TMS, Healthy Volunteer, HV
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 40 participants
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- Feb 2003
- Study completion
- Mar 2004
- First posted
- 17 Feb 2003 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- Normal volunteers will be male or female, aged 18 to 55 at protocol entry without any of the exclusion criteria described below.
Key exclusion criteria (12 listed)
- are pregnant (tested with urine pregnancy test).
- have severe coronary disease.
- have metal anywhere in the cranium except the mouth.
- have intracardiac lines.
- have increased intracranial pressure as expressed by the presence of papilledema.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 11180020Burstein 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. doi: 10.1067/mcp.2000.111530.
- Background: PubMed 10840401Cantello 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. doi: 10.1111/j.1528-1157.2000.tb00230.x.
- Background: PubMed 9305361Chen R, Samii A, Canos M, Wassermann EM, Hallett M. Effects of phenytoin on cortical excitability in humans. Neurology. 1997 Sep;49(3):881-3. doi: 10.1212/wnl.49.3.881.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Healthy, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00054990, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2008.