Phenytoin and Driving Safety: A Randomized, Controlled Cross-Over Study

NCT00581893 | Completed Phase 4 Results DMC

• 2 other identifiers: 2005127125R49CE721682-05
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cognitive Measures; Driving Simulator Performance

Keywords

epilepsy; cognitive impairment; driving simulation; cross-over study

Outcome Measures

Primary Outcomes (1)

• Number of Subjects Who Had a Driving Simulator Crash Event

  Number of subjects who had a crash event during the driving simulator test.

  1 month

Study Arms (2)

1

EXPERIMENTAL

Phenytoin administration

Drug: Phenytoin

2

PLACEBO COMPARATOR

Placebo

Drug: Placebo oral capsule

Interventions

Phenytoin DRUG

Phenytoin will be dosed to a target dose of 5 mg/kg qhs for one month

Also known as: Dilantin

1

Placebo oral capsule DRUG

Placebo

2

Eligibility Criteria

• Age: 25 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Iowa: lead

Study Sites (1)

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Related Publications (1)

• 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.

  BACKGROUND

MeSH Terms

Conditions

Epilepsy; Cognitive Dysfunction

Interventions

Phenytoin

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Hydantoins; Imidazolidines; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

The very small sample size of evaluable subjects prevents definitive conclusions on the safety hazards of phenytoin for driving performance.

Results Point of Contact

• Title: Erik St. Louis
• Organization: University of Iowa

StLouis.Erik@mayo.edu

507-266-7456

Study Officials

• Erik K St. Louis, M.D.

  University of Iowa

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor (Clinical)

Study Record Dates

• First Submitted: December 19, 2007
• First Posted: December 28, 2007
• Study Start: August 1, 2005
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2008
• Last Updated: July 1, 2021
• Results First Posted: July 1, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)