Protocol Number: 03-N-0147

Title:

Effects of AMPA Receptor Blockade on Human Cortical Excitability - A Pilot Study

Number:

03-N-0147

Summary:

This study will use transcranial magnetic stimulation (TMS) and electroencephalography (EEG) to test the safety of an experimental anti-epileptic drug called Talampanel and learn how it affects brain activity. Talampanel blocks a type of brain receptor called AMPA; inhibiting this receptor may result in anti-seizure activity.

TMS stimulates the outer part of the brain, called the cortex. For this procedure, an insulated wire coil is placed on the subject's 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 muscle twitching in the face, arm, or leg.

EEG records the electrical activity of the brain, in the form of brain waves. For this procedure, electrodes (metal discs with a conductive gel) attached to wires are affixed to the scalp with a paste and the brain activity is recorded.

Healthy normal volunteers between 18 and 45 years of age may participate in this study. Candidates will be screened with a physical and neurological examination, electrocardiogram (EKG), blood tests, and blood pressure measurement. Women who are pregnant or nursing are excluded from the study.

Participants will come to the NIH Clinical Center for three testing sessions, at least 1 week apart, and a final follow-up visit. The procedure for each test session is as follows:

7 AM - Blood pressure is measured, EKG and EEC leads are placed, a heparin lock is inserted, and a blood sample is drawn. The heparin lock is a thin needle enclosed in a thin plastic tube. The needle guides the tube into a vein and is then removed, leaving the tube in place. The indwelling tube allows multiple blood samples to be drawn without repeated needle sticks.

8 - 9 AM - TMS followed by EEG recording.

9 AM - Administration of Talampanel or placebo (pill with no active ingredient) by mouth.

10 AM - Blood sample #2.

10 AM -11 AM - TMS, followed by EEG recording every 5 minutes.

11 AM - Blood sample #3.

12 PM - Blood sample #4.

11 AM - 1 PM - EEG recording every 5 minutes/

4 PM - Blood sample #5.

5 PM - Discharge from Clinical Center.

At the final follow-up visit, the participant will talk with the doctor and have one final blood draw.

Sponsoring Institute:

National Institute of Neurological Disorders and Stroke (NINDS)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

Study subjects must be 18-45 years old (inclusive).

Study subjects must give informed consent in writing prior to entering the study.

Study subjects must be able to participate for the full term of the trial.

EXCLUSION CRITERIA:

Any of the following conditions is cause for exclusion from the study:

Any illness requiring chronic drug therapy with one of the following drugs: Depakote (valproic acid), Hismanal (astemizole), Propulsid (cisapride), Allegra (fexofenadine), Seldane (terfenadine), Luvox (fluvoxamine), Felbamate (felbatol), Tiagabine (vigabatrin), hepatic enzyme induces such as Tagamet (cimetidine), and -azole antifungals such as Flagyl (metronidazole), Diflucan (fluconazole), and Nizoral (ketoconazole).

History of a psychiatric disorder, under the care of a psychiatrist, or on medications for treatment of a psychiatric disorder.

Known sensitivity or allergy to talampanel or related compounds.

Use of illicit drugs, binge drinking, or alcoholism as per medical history inventory.

Exposure to any other investigational drug within 12 weeks prior to randomization.

Magnetic stimulation will not be performed in people who have pacemakers, implanted pumps or stimulators, or who have metal objects inside the eye or skull.

Being under the age of 18 years or over the age of 45 years.

Pregnant or lactating.

Cardiac, pulmonary, or neurological problems as determined by medical history, EKG, and examination by a physician.

Special Instructions: Currently Not Provided

Keywords:

Antiepileptic Drug

Neuroprotection

Seizure Disorder

TMS Stimulation

EEG

AMPA Antagonist

Dosing

Transcranial Magnetic Stimulation

Recruitment Keywords:

Healthy Volunteer

HV

Conditions:

Healthy

Investigational Drug(s):

Talampanel

Investigational Device(s):

None

Contacts:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:

Anand S, Hotson J. Transcranial magnetic stimulation: Neurophysiological applications and safety. Brain Cogn. 2002 Dec;50(3):366-86. PMID: 12480484

Belayev L, et al. Talampanel, a novel noncompetitive AMPA antagonist, is neuroprotective after traumatic brain injury in rats. J Neurotrauma. 2001 Oct;18(10):1031-8. PMID: 11686490

Berardelli A, et al. Pathophysiology of bradykinesia in Parkinson's disease. Brain. 2001 Nov;124(Pt 11):2131-46. Review. PMID: 11673316

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
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