HealthyPhase 2NCT00057460
Effect of Talampanel (an AMPA Receptor Blocker) on Brain Activity
A Phase 2 study testing Talampanel in people with Healthy, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Talampanel
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2003to May 2006
- Phase
- Phase 2
- 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
- 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.
Who cannot join
- 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 inducers 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.
Show all 10Show fewer
- 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.
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: Effects of AMPA Receptor Blockade on Human Cortical Excitability - A Pilot Study
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.
Read more
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.
Read the 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.
- Conditions
- Healthy
- Being tested
- Talampanel
- Keywords
- Antiepileptic Drug, Neuroprotection, Seizure Disorder, TMS Stimulation, EEG, AMPA Antagonist, Dosing, Transcranial Magnetic Stimulation, Healthy Volunteer, HV
- Medical subject headings
- Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TalampanelDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2003 (estimated)
- Study startApr 2003
- Study completionMay 2006
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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Enrolment
- 25 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00057460
- Sponsor's protocol ID
- 030147
- Other IDs
- 03-N-0147
- Status last verified
- May 2006
- First submitted
- 2 Apr 2003
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Anand S, Hotson J. Transcranial magnetic stimulation: neurophysiological applications and safety. Brain Cogn. 2002 Dec;50(3):366-86. doi: 10.1016/s0278-2626(02)00512-2.
PubMed 12480484Belayev L, Alonso OF, Liu Y, Chappell AS, Zhao W, Ginsberg MD, Busto R. Talampanel, a novel noncompetitive AMPA antagonist, is neuroprotective after traumatic brain injury in rats. J Neurotrauma. 2001 Oct;18(10):1031-8. doi: 10.1089/08977150152693728.
PubMed 11686490Berardelli A, Rothwell JC, Thompson PD, Hallett M. Pathophysiology of bradykinesia in Parkinson's disease. Brain. 2001 Nov;124(Pt 11):2131-46. doi: 10.1093/brain/124.11.2131.
PubMed 11673316
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
- Effects of AMPA Receptor Blockade on Human Cortical Excitability - A Pilot Study
- ClinicalTrials.gov ID
- NCT00057460
- Acronym / sponsor ID
- 030147
- Conditions
- Healthy
- Keywords
- Antiepileptic Drug, Neuroprotection, Seizure Disorder, TMS Stimulation, EEG, AMPA Antagonist, Dosing, Transcranial Magnetic Stimulation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- Apr 2003
- Study completion
- May 2006
- First posted
- 2 Apr 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 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.
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 design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (10 listed)
- 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 inducers 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Talampanel | Drug | – |
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 12480484Anand S, Hotson J. Transcranial magnetic stimulation: neurophysiological applications and safety. Brain Cogn. 2002 Dec;50(3):366-86. doi: 10.1016/s0278-2626(02)00512-2.
- Background: PubMed 11686490Belayev L, Alonso OF, Liu Y, Chappell AS, Zhao W, Ginsberg MD, Busto R. Talampanel, a novel noncompetitive AMPA antagonist, is neuroprotective after traumatic brain injury in rats. J Neurotrauma. 2001 Oct;18(10):1031-8. doi: 10.1089/08977150152693728.
- Background: PubMed 11673316Berardelli A, Rothwell JC, Thompson PD, Hallett M. Pathophysiology of bradykinesia in Parkinson's disease. Brain. 2001 Nov;124(Pt 11):2131-46. doi: 10.1093/brain/124.11.2131.
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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?
A Phase 2 study testing Talampanel in people with 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 3 inclusion and 10 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 NCT00057460, 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.