Phenytoin and Driving Safety: A Randomized, Controlled Cross-Over Study
Condition: Cognitive Measures; Driving Simulator Performance
Intervention: Phenytoin; Placebo oral capsule
Intervention description: Phenytoin will be dosed to a target dose of 5 mg/kg qhs for one month; Placebo
Intervention MeSH terms: Phenytoin
Phase: Phase 4
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 20.0
Sex: All
Minimum age: 25 Years
Maximum age: 60 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: epilepsy; cognitive impairment; driving simulation; cross-over study

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. 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.
    

Eligibility 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.