Cognitive MeasuresPhase 4NCT00581893
Phenytoin and Driving Safety: A Randomized, Controlled Cross-Over Study
A Phase 4 study testing Phenytoin in people with Cognitive Measures and Driving Simulator Performance, run by University of Iowa at 1 site in United States.
Trial summary
Automobile driving is a crucial aspect of everyday life, yet vehicular crashes represent a serious public health problem. Patients with epilepsy are at elevated risk for automobile crashes, causing great personal suffering and financial costs to society. Read more about this study
- Who is it for?
- Ages 25 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Cognitive Measures, Driving Simulator Performance
- What is being tested?
- Phenytoin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2005to Dec 2008
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 25 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Anticipating a 10-15% drop-out rate, we will induct 30 neurologically normal subjects (age 18 (21) -60) to obtain 25 evaluable subjects who are legally licensed to drive in their state of residence and have been actively driving under appropriate legal guidelines for at least 5 years (to minimize performance variations of novice drivers).
- Because this study is intended to determine the potential effects of phenytoin on driving performance, a relatively healthy cohort of patients must be chosen. Chronic medical or psychiatric conditions could cause significant alterations in driving performance independent of those caused by phenytoin, which would complicate interpretation of performance impairments.
Who cannot join
- Subjects who are younger than 18 or older than 60
- Have history of prior seizures, family history of epilepsy, or prior history of head injury
- Have a known history of prior drug or alcohol abuse or unwillingness to abstain from drug or alcohol use during the study period
- Have a past or current active neurological or psychiatric disorder that could impair cognitive or driving performance (i.e. baseline IQ < 90, dementia, mental retardation, stroke, severe head injury, schizophrenia, active clinical depression, progressive brain tumor).
- Subjects who have a chronic medical condition (i.e. diabetes mellitus, renal insufficiency, congestive heart failure, hepatic dysfunction, hematologic condition, HIV)
- Taking medications known to affect the central nervous system (i.e. baseline pre-study treatment with antiepileptic drug, anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, narcotics and tranquilizers)
- Regularly use over-the-counter cough suppressants, antihistamines, or sleep aids; or who ingest over 7 cups of daily coffee or currently smoke cigarettes.
- Subjects will be excluded if they cannot complete SIREN testing or neuropsychological instruments because of visual or hearing impairment (history or screening discovery of corrected visual acuity of less than 20/50) or other physical disability, or if they have a history of severe motion sickness as an adult-a marker for patients who develop simulator sickness and therefore cannot participate in SIREN testing.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
About this study
Automobile driving is a crucial aspect of everyday life, yet vehicular crashes represent a serious public health problem. Patients with epilepsy are at elevated risk for automobile crashes, causing great personal suffering and financial costs to society. Most collisions involving epileptic drivers are not seizure related but may instead result from cognitive effects upon driving performance of epilepsy and antiepileptic drugs (AEDs). Several million American drivers take AEDs for treatment of medical conditions besides epilepsy and may also be at risk for cognitive impairments that can reduce driving performance. Empirical evidence of the effects of AEDs on driving performance would enable development of driving guidelines that could lower the risk of injurious motor vehicle collisions; however, this evidence is currently lacking. The broad goal of our project is to determine the specific effects of the most commonly utilized AED, phenytoin, by assessing driving performance and cognitive abilities in neurologically normal volunteers taking phenytoin in a randomized, double-blind, placebo-controlled, crossover study. Our proposed experiments will assess: (1) cognitive functions using standardized neuropsychological tests (of attention, perception, memory, and executive functions), (2) driving performance during phenytoin and placebo administration, and (3) the effects of phenytoin-related cognitive performance upon driving performance. To measure driving performance, we will use a state-of-the-art fixed-base interactive driving simulator that allows us to observe driver errors in an environment that is challenging yet safe for the driver and tester, under conditions of optimal stimulus and response control. The results of this study of 30 drivers treated with phenytoin and placebo will increase the understanding of the role of AED-related cognitive impairment on driving safety errors. A better understanding of the impact of AEDs upon driving performance is necessary to rationally develop interventions that could help prevent crashes by drivers treated with AEDs.
Read the detailed description
Patients with epilepsy are at elevated risk for automobile crashes, causing great personal suffering and financial costs to society. Most collisions involving epileptic drivers are not seizure related but may instead result from cognitive effects upon driving performance of epilepsy and antiepileptic drugs (AEDs). Several million American drivers take AEDs for treatment of medical conditions besides epilepsy and may also be at risk for cognitive impairments that can reduce driving performance. Empirical evidence of the effects of AEDs on driving performance would enable development of driving guidelines that could lower the risk of injurious motor vehicle collisions; however, this evidence is currently lacking.
The broad goal of the current project is to determine the specific effects of AEDs on cognitive function and driving performance. To address this goal we will assess driving performance and cognitive abilities in neurologically normal volunteers taking phenytoin (Dilantin), the most commonly prescribed AED. Effects of phenytoin on driving performance and cognition will be addressed in a randomized, double-blind, placebo-controlled, crossover study. Driver cognition will be assessed using a battery of neuropsychological tests. Driving performance will be objectively assessed in all participants on standardized tasks enacted in a state-of-the-art driving simulator. Our 3 Specific Aims are:
Aim 1: To assess the effects of phenytoin on cognitive abilities that are crucial to the driving task, including perception, attention, memory, and executive function.
Hypothesis 1: A driver's cognitive abilities will decline during steady-state phenytoin administration compared to placebo. Drivers with higher blood levels of phenytoin will show greater decline.
Aim 2: To assess effects of phenytoin on driving performance and safety errors in a state-of-the-art driving simulator.
Hypothesis 2: Driving performance will decline and driver safety errors will increase during phenytoin administration compared to placebo. Drivers with higher blood levels of phenytoin will show greater impairments of driving.
Aim 3: To assess the effects of phenytoin-related cognitive impairments upon driving performance in a state-of-the-art driving simulator.
Hypothesis 3. Impairments of cognitive function affecting perception, attention, memory, executive function, and arousal will increase the likelihood of driver errors that may lead to a crash.
Our hypotheses would be supported if the drivers taking phenytoin, as opposed to placebo, demonstrate worse cognitive performance on neuropsychological tests, and more safety errors and crashes in the simulator. The hypotheses would also be supported if drivers with higher phenytoin levels show greater impairments of cognition and driving. Once the effects of phenytoin on driving performance are demonstrated in this project, we will have evidence to support more comprehensive research addressing specific dosing and serum levels and acute versus chronic administration.
There is currently no evidence concerning the effects of phenytoin on driving performance. Accurate driving performance data on patients receiving phenytoin would allow determination of fair and accurate criteria for making recommendations to drive or not to drive affecting millions of patients taking AEDS for epilepsy and other conditions. These data could also help reduce the risk of car crashes due to medication side effects.
- Conditions
- Cognitive Measures, Driving Simulator Performance
- Being tested
- Phenytoin, Placebo oral capsule
- Keywords
- epilepsy, cognitive impairment, driving simulation, cross-over study
- Medical subject headings
- Epilepsy, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PhenytoinDrug
Also called Dilantin
Phenytoin will be dosed to a target dose of 5 mg/kg qhs for one month
Placebo oral capsuleDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Phenytoin administration Receives: Drug: Phenytoin |
| 2 | Placebo comparator | Placebo Receives: Drug: Placebo oral capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects Who Had a Driving Simulator Crash Event
Number of subjects who had a crash event during the driving simulator test.
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Dec 2007 (estimated)
- Study startAug 2005
- Primary completionDec 2008
- Study completionDec 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cognitive MeasuresStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Iowa
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Erik St. Louis, University of Iowa
- Investigators
- Erik K St. Louis, M.D., Principal investigator, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00581893
- Sponsor's protocol ID
- 200512712
- Other IDs
- 5R49CE721682-05
- Status last verified
- Jun 2021
- First submitted
- 19 Dec 2007
- Last updated
- 1 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
St. Louis EK, McEvoy S, Shi QC, Rizzo M. Useful Field of View impairment in partial epilepsy. Unpublished observations and submitted abstract to 3rd International Driving Symposium on Human Factors in Driving Asssessment, Training, and Vehicle Design, Rockport, Maine, June, 2005.
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phenytoin and Driving Safety: A Randomized, Controlled Cross-Over Study
- ClinicalTrials.gov ID
- NCT00581893
- Acronym / sponsor ID
- 200512712
- Conditions
- Cognitive Measures, Driving Simulator Performance
- Keywords
- epilepsy, cognitive impairment, driving simulation, cross-over study
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of IowaUniversity, hospital or other
- Study start
- Aug 2005
- Primary completion
- Dec 2008 (actual)
- Study completion
- Dec 2008 (actual)
- First posted
- 28 Dec 2007 (estimated)
- Results
- Posted 1 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Automobile driving is a crucial aspect of everyday life, yet vehicular crashes represent a serious public health problem. Patients with epilepsy are at elevated risk for automobile crashes, causing great personal suffering and financial costs to society. Most collisions involving epileptic drivers are not seizure related but may instead result from cognitive effects upon driving performance of epilepsy and antiepileptic drugs (AEDs). Several million American drivers take AEDs for treatment of medical conditions besides epilepsy and may also be at risk for cognitive impairments that can reduce driving performance. Empirical evidence of the effects of AEDs on driving performance would enable development of driving guidelines that could lower the risk of injurious motor vehicle collisions; however, this evidence is currently lacking. The broad goal of our project is to determine the specific effects of the most commonly utilized AED, phenytoin, by assessing driving performance and cognitive abilities in neurologically normal volunteers taking phenytoin in a randomized, double-blind, placebo-controlled, crossover study. Our proposed experiments will assess: (1) cognitive functions using standardized neuropsychological tests (of attention, perception, memory, and executive functions), (2) driving performance during phenytoin and placebo administration, and (3) the effects of phenytoin-related cognitive performance upon driving performance. To measure driving performance, we will use a state-of-the-art fixed-base interactive driving simulator that allows us to observe driver errors in an environment that is challenging yet safe for the driver and tester, under conditions of optimal stimulus and response control. The results of this study of 30 drivers treated with phenytoin and placebo will increase the understanding of the role of AED-related cognitive impairment on driving safety errors. A better understanding of the impact of AEDs upon driving performance is necessary to rationally develop interventions that could help prevent crashes by drivers treated with AEDs.
Detailed description
Patients with epilepsy are at elevated risk for automobile crashes, causing great personal suffering and financial costs to society. Most collisions involving epileptic drivers are not seizure related but may instead result from cognitive effects upon driving performance of epilepsy and antiepileptic drugs (AEDs). Several million American drivers take AEDs for treatment of medical conditions besides epilepsy and may also be at risk for cognitive impairments that can reduce driving performance. Empirical evidence of the effects of AEDs on driving performance would enable development of driving guidelines that could lower the risk of injurious motor vehicle collisions; however, this evidence is currently lacking.
The broad goal of the current project is to determine the specific effects of AEDs on cognitive function and driving performance. To address this goal we will assess driving performance and cognitive abilities in neurologically normal volunteers taking phenytoin (Dilantin), the most commonly prescribed AED. Effects of phenytoin on driving performance and cognition will be addressed in a randomized, double-blind, placebo-controlled, crossover study. Driver cognition will be assessed using a battery of neuropsychological tests. Driving performance will be objectively assessed in all participants on standardized tasks enacted in a state-of-the-art driving simulator. Our 3 Specific Aims are:
Aim 1: To assess the effects of phenytoin on cognitive abilities that are crucial to the driving task, including perception, attention, memory, and executive function.
Hypothesis 1: A driver's cognitive abilities will decline during steady-state phenytoin administration compared to placebo. Drivers with higher blood levels of phenytoin will show greater decline.
Aim 2: To assess effects of phenytoin on driving performance and safety errors in a state-of-the-art driving simulator.
Hypothesis 2: Driving performance will decline and driver safety errors will increase during phenytoin administration compared to placebo. Drivers with higher blood levels of phenytoin will show greater impairments of driving.
Aim 3: To assess the effects of phenytoin-related cognitive impairments upon driving performance in a state-of-the-art driving simulator.
Hypothesis 3. Impairments of cognitive function affecting perception, attention, memory, executive function, and arousal will increase the likelihood of driver errors that may lead to a crash.
Our hypotheses would be supported if the drivers taking phenytoin, as opposed to placebo, demonstrate worse cognitive performance on neuropsychological tests, and more safety errors and crashes in the simulator. The hypotheses would also be supported if drivers with higher phenytoin levels show greater impairments of cognition and driving. Once the effects of phenytoin on driving performance are demonstrated in this project, we will have evidence to support more comprehensive research addressing specific dosing and serum levels and acute versus chronic administration.
There is currently no evidence concerning the effects of phenytoin on driving performance. Accurate driving performance data on patients receiving phenytoin would allow determination of fair and accurate criteria for making recommendations to drive or not to drive affecting millions of patients taking AEDS for epilepsy and other conditions. These data could also help reduce the risk of car crashes due to medication side effects.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: PhenytoinPhenytoin administration |
| 2 | Placebo comparator | Drug: Placebo oral capsulePlacebo |
Who may qualify
- Ages
- 25 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Anticipating a 10-15% drop-out rate, we will induct 30 neurologically normal subjects (age 18 (21) -60) to obtain 25 evaluable subjects who are legally licensed to drive in their state of residence and have been actively driving under appropriate legal guidelines for at least 5 years (to minimize performance variations of novice drivers).
- Because this study is intended to determine the potential effects of phenytoin on driving performance, a relatively healthy cohort of patients must be chosen. Chronic medical or psychiatric conditions could cause significant alterations in driving performance independent of those caused by phenytoin, which would complicate interpretation of performance impairments.
Key exclusion criteria (8 listed)
- Subjects who are younger than 18 or older than 60
- Have history of prior seizures, family history of epilepsy, or prior history of head injury
- Have a known history of prior drug or alcohol abuse or unwillingness to abstain from drug or alcohol use during the study period
- Have a past or current active neurological or psychiatric disorder that could impair cognitive or driving performance (i.e. baseline IQ < 90, dementia, mental retardation, stroke, severe head injury, schizophrenia, active clinical depression, progressive brain tumor).
- Subjects who have a chronic medical condition (i.e. diabetes mellitus, renal insufficiency, congestive heart failure, hepatic dysfunction, hematologic condition, HIV)
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 |
|---|---|---|
| PhenytoinAlso: DilantinPhenytoin will be dosed to a target dose of 5 mg/kg qhs for one month | Drug | 1 |
| Placebo oral capsulePlacebo | Drug | 2 |
Primary outcome
Number of Subjects Who Had a Driving Simulator Crash Event
Time frame: 1 month
Number of subjects who had a crash event during the driving simulator test.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- BackgroundSt. Louis EK, McEvoy S, Shi QC, Rizzo M. Useful Field of View impairment in partial epilepsy. Unpublished observations and submitted abstract to 3rd International Driving Symposium on Human Factors in Driving Asssessment, Training, and Vehicle Design, Rockport, Maine, June, 2005.
- Individual participant dataSharing planned: No
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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.
Erik K St. Louis, M.D. principal investigator
University of Iowa
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Phenytoin in people with Cognitive Measures and Driving Simulator Performance, run by University of Iowa 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 2 inclusion and 8 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 1 Jul 2021. 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. Some participants in this study may receive a placebo. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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.
What does the primary outcome measure?
Number of Subjects Who Had a Driving Simulator Crash Event (time frame: 1 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00581893, which also lists 1 linked publication.
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 1 Jul 2021.