Phenytoin and Driving Safety: A Randomized, Controlled Cross-Over Study
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Iowa
-
Iowa City, Iowa, United States, 52242
- University of Iowa Hospitals and Clinics
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Placebo Comparator: 2
Placebo
|
Placebo
|
|
Experimental: 1
Phenytoin administration
|
Phenytoin will be dosed to a target dose of 5 mg/kg qhs for one month
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
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.
|
1 month
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Erik K St. Louis, M.D., University of Iowa
Publications and helpful links
General 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 record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 200512712
- 5R49CE721682-05 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.