Ignite Creation Date:
2024-05-05 @ 11:28 AM
Last Modification Date:
2024-10-26 @ 9:08 AM
Study NCT ID:
NCT00057460
Status:
COMPLETED
Last Update Posted:
2008-03-04
First Post:
2003-04-02
Brief Title:
Effect of Talampanel an AMPA Receptor Blocker on Brain Activity
Sponsor:
National Institute of Neurological Disorders and Stroke NINDS
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Effects of AMPA Receptor Blockade on Human Cortical Excitability - A Pilot Study
Status:
COMPLETED
Status Verified Date:
2006-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 subjects 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
TMS stimulates the outer part of the brain called the cortex For this procedure an insulated wire coil is placed on the subjects 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
Detailed Description:
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 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 03-N-0147 | None | None | None |