Effect of Talampanel (an AMPA Receptor Blocker) on Brain Activity

2014-08-27 03:55:21 | BioPortfolio


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.


Objectives. The purpose of this pilot study is to identify human neurophysiological parameters that are sensitive to talampanel, as assessed by transcranial magnetic stimulation (TMS) and electroencephalography (EEG). Talampanel is a highly selective, orally active antagonist of the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor. The study will test two hypotheses: (1) talampanel will, in a dose-dependent fashion, suppress the motor-evoked potential (MEP) amplitude and intracortical facilitation as determined by TMS, and (2) talampanel will, in a dose-dependent fashion, cause alterations in EEG power within specific frequency bands. We plan to administer a low (25 mg) and high (50 mg) dose of talampanel and placebo to normal volunteers and measure various TMS and EEG parameters that we hypothesize may be influenced by AMPA receptor blockade. We will simultaneously assay serum levels of talampanel. We will use statistical tests to correlate changes in the TMS and EEG measures with drug concentration. The results of this study will allow us to undertake a follow-up study in which we will determine the effects of AMPA receptor blockade by talampanel on human motor and cognitive function. Our ultimate goal is to determine whether drug-induced blockade of AMPA receptors can be achieved without unacceptable neurological impairment.

Study population. This will be a blinded and placebo-controlled pilot study using 12 normal volunteers.

Design. Normal volunteers accepted into the study will be subjected to the following exams: (a) TMS determination of MEP amplitude and paired-pulse testing at baseline and at peak serum levels after drug or placebo administration, (b) digital EEG recording for 1 h at baseline before administration of drug or placebo and during a period of 3 h after administration. Samples for serum chemistry, liver function tests, hematology, and urinalysis will be obtained at admission, at discharge, and in every clinic visit during the study. Blood samples for determining serum talampanel levels will be obtained at 1, 2, 3, and 8 h after drug administration. MEPs at interstimulus intervals of 2 to 20 ms will be compared among subjects before and after drug administration, by a repeated measures analysis of variance. Talampanel levels will be correlated with MEP amplitudes by regression analysis.

Clinical endpoint. This pilot study will identify information on the best TMS interstimulus interval or intervals for measuring changes in cortical excitability after AMPA blockade, as well as the EEG frequency band most sensitive to AMPA blockade with talampanel. Because talampanel is a highly selective AMPA receptor antagonist, we will be able to infer that the parameters that are sensitive to talampanel can be used as empirical assays of AMPA receptor function in humans.

Study Design

Endpoint Classification: Safety/Efficacy Study, Primary Purpose: Treatment






National Institute of Neurological Disorders and Stroke (NINDS)
United States




National Institutes of Health Clinical Center (CC)

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:55:21-0400

Clinical Trials [13 Associated Clinical Trials listed on BioPortfolio]

A Study to Investigate the Absorption, Metabolism and Excretion of Talampanel

The purpose of this study is to characterize the chemical breakdown and excretion of talampanel and its break down products in plasma, feces, and urine of healthy human volunteers.

Multicenter Trial for Adults With Partial Seizures

To compare seizure frequency in patients with refactory partial seizures (with or without generalization) who are taking Talampanel versus placebo as an add-on therapy to other licensed co...

Talampanel for Amyotrophic Lateral Sclerosis (ALS)

The purpose of this study is to assess the efficacy, tolerability and safety of oral administration of talampanel compared to a placebo in subjects with ALS.

A Phase 1 Study to Investigate the Effects of Talampanel on the Heart Rhythm

The purpose of this study is to assess whether multiple doses of Talampanel increase the QT interval when compared to placebo

Talampanel in Treating Patients With Recurrent High-Grade Glioma

RATIONALE: Drugs used in chemotherapy such as talampanel use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: This phase II trial is studying how wel...

PubMed Articles [4418 Associated PubMed Articles listed on BioPortfolio]

Peace, Love, Field Day: An Innovative Approach to Cultivating Healthy Academic Communities.

The American Nurses Association declared 2017 the Year of the Healthy Nurse. In an effort to promote a healthy academic environment, faculty and staff in institutions of higher learning should serve a...

Analysis of Cranial Morphology of Healthy Infants Using Homologous Modeling.

Data on cranial morphology of healthy individuals can be used as the guide in the treatment of cranial deformity. There are many reports analyzing the cranial morphology of healthy children in the pas...

Ontario's Healthy Babies Healthy Children Screen tool: identifying postpartum families in need of home visiting services in Ottawa, Canada.

Across Ontario, the Healthy Babies Healthy Children (HBHC) postpartum screening tool is routinely used to identify families with potential risk of negative development outcomes for children.

Domains and Measurements of Healthy Aging in Epidemiological Studies: A Review.

Few studies have recommended the essential domains of healthy aging and their relevant measurement to assess healthy aging comprehensively. This review is to fill the gap, by conducting a literature r...

Magnetic Resonance Imaging of Cerebrovascular Reactivity in Healthy Adolescents.

Cerebrovascular reactivity (CVR), an important measure of cerebrovascular health in adults, has not been examined in healthy adolescents. Beyond the direct importance of understanding CVR in healthy y...

Medical and Biotech [MESH] Definitions

Healthy People Programs are a set of health objectives to be used by governments, communities, professional organizations, and others to help develop programs to improve health. It builds on initiatives pursued over the past two decades beginning with the 1979 Surgeon General's Report, Healthy People, Healthy People 2000: National Health Promotion and Disease Prevention Objectives, and Healthy People 2010. These established national health objectives and served as the basis for the development of state and community plans. These are administered by the Office of Disease Prevention and Health Promotion (ODPHP). Similar programs are conducted by other national governments.

Governmental guidelines and objectives pertaining to public food supply and nutrition including recommendations for healthy diet and changes in food habits to ensure healthy diet.

Surgical reinnervation of a denervated peripheral target using a healthy donor nerve and/or its proximal stump. The direct connection is usually made to a healthy postlesional distal portion of a non-functioning nerve or implanted directly into denervated muscle or insensitive skin. Nerve sprouts will grow from the transferred nerve into the denervated elements and establish contact between them and the neurons that formerly controlled another area.

Process of evaluating the health of a patient and determining if they are healthy enough for surgery.

Dietary patterns which have been found to be important in reducing disease risk.

More From BioPortfolio on "Effect of Talampanel (an AMPA Receptor Blocker) on Brain Activity"

Quick Search


Relevant Topics

Pharmacy is the science and technique of preparing as well as dispensing drugs and medicines. It is a health profession that links health sciences with chemical sciences and aims to ensure the safe and effective use of pharmaceutical drugs. The scope of...

Alzheimer's Disease
Of all the types of Dementia, Alzheimer's disease is the most common, affecting around 465,000 people in the UK. Neurons in the brain die, becuase  'plaques' and 'tangles' (mis-folded proteins) form in the brain. People with Al...

Searches Linking to this Trial