Phenytoin and Driving Safety

The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2007 by University of Iowa.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
University of Iowa
ClinicalTrials.gov Identifier:
NCT00581893
First received: December 19, 2007
Last updated: December 27, 2007
Last verified: December 2007
  Purpose

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.


Condition Intervention Phase
Cognitive Measures
Driving Simulator Performance
Drug: Phenytoin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Official Title: Phenytoin and Driving Safety

Resource links provided by NLM:


Further study details as provided by University of Iowa:

Primary Outcome Measures:
  • Number of driving simulator crash events [ Time Frame: Open-ended ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Measures of cognition assessed in the on-phenytoin condition [ Time Frame: Open-ended ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 30
Study Start Date: August 2005
Estimated Study Completion Date: December 2008
Estimated Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Phenytoin administration
Drug: Phenytoin
Phenytoin will be dosed to a target dose of 5 mg/kg qhs for one month
Other Name: Dilantin

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.

  Eligibility

Ages Eligible for Study:   25 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00581893

Contacts
Contact: Erik K. St. Louis, M.D. 319-384-6084 erik-stlouis@uiowa.edu
Contact: Ellen Paul, RN 319-353-8463 ellen-paul@uiowa.edu

Locations
United States, Iowa
University of Iowa Hospitals and Clinics Recruiting
Iowa City, Iowa, United States, 52242
Contact: Erik K. St. Louis, M.D.    319-384-6084    erik-stlouis@uiowa.edu   
Contact: Ellen Paul, RN    319-353-8463    ellen-paul@uiowa.edu   
Principal Investigator: Erik K. St. Louis, M.D.         
Sub-Investigator: Matthew Rizzo, M.D.         
Sub-Investigator: Mark A. Granner, M.D.         
Sub-Investigator: Miriam B. Zimmerman, Ph.D.         
Sub-Investigator: Gary Milavetz, Pharm.D.         
Sponsors and Collaborators
University of Iowa
Investigators
Principal Investigator: Erik K St. Louis, M.D. University of Iowa
  More Information

Additional Information:
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.

Responsible Party: Erik K. St. Louis, M.D., University of Iowa Hospitals and Clinics
ClinicalTrials.gov Identifier: NCT00581893     History of Changes
Other Study ID Numbers: 200512712, 5 R49 CE721682-05
Study First Received: December 19, 2007
Last Updated: December 27, 2007
Health Authority: United States: Institutional Review Board

Keywords provided by University of Iowa:
epilepsy
cognitive impairment
driving simulation
cross-over study

Additional relevant MeSH terms:
Phenytoin
Anticonvulsants
Cardiovascular Agents
Central Nervous System Agents
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Sodium Channel Blockers
Therapeutic Uses
Voltage-Gated Sodium Channel Blockers

ClinicalTrials.gov processed this record on October 20, 2014