Effect of Armodafinil on Simulated Driving
Condition: Healthy Volunteers
Study type: Interventional
Phase: Phase 1

Summary: 
      Sleep deprivation slows reaction time, reduces vigilance and impairs judgment and information
      processing. Chronic effects include metabolic dysfunction, cardiovascular disease and cancer.
      Sleep deprivation affects quality of life when it causes errors in judgment, whether these
      occur behind the wheel of an automobile or in a hospital. Armodafinil, a non-amphetamine
      wakefulness promoting medication, indicated for excessive sleepiness associated with
      obstructive sleep apnea, narcolepsy, and shift work sleep disorder is used to mitigate the
      effects of sleep deprivation.

      This study will characterize the effect of armodafinil on driving simulator performance. The
      effects of armodafinil compared to placebo will be studied in a double blind crossover trial
      involving 10 healthy subjects with serial assessments at baseline and after extensive sleep
      deprivation. Using simultaneous electroencephalogram (EEG) recording during simulated driving
      and neurocognitive assessments of vigilance, the relationship between brain activity and
      cognitive performance will be established.
    

Detailed description: 
      On the first study day, the subjects will come to the Clinical Research Center (CRC) early in
      the morning. In the first 90 minutes (acclimation session) of the study day EEG electrodes
      will be applied and EEG signals will be measured continuously throughout the session.
      Subjects will be instructed of the controls and operation of the driving simulator and
      perform a 10 minute test drive to familiarize with it. Afterwards they will perform a battery
      of cognitive tests including the Motor Praxis Task, the Visual Object Learning Test, the
      Fractal-2-Back, the Abstract Matching, the Line Orientation Test, the Digit-Symbol
      Substitution Task, the Balloon Analog Risk Test, and the Psychomotor Vigilance Test to get
      familiar with the cognitive tests. The cognitive battery will last approximately 25 minutes.
      The collected data of the conditioning session won't be part of the analysis. The purpose of
      the session is that subjects adapt to the measures.

      Following the acclimation session, the resting baseline for the subjects will be measured
      which will consist of a simultaneous assessment of cognitive performance and brain activity.
      The subjects will first drive for 30 minutes on the driving simulator to establish a resting
      baseline of the driving performance. Afterwards a resting baseline for cognitive tests will
      be established to measure attention, vigilance, risk-taking and decision-making. EEG will be
      recorded concurrently during driving and cognitive tests. No blood samples will be taken
      during the assessment of the resting baseline. Subjects will be discharged from the CRC after
      completion of the baseline session (approximately 2 hours) until the evening. During this
      time subjects are not allowed to sleep and they will be informed to not consume any caffeine
      containing products (e.g. Red Bull, coffee). Upon return to the CRC, the subjects will be
      sleep deprived and supervised by at least one of the study coordinators and at least one
      additional person to make sure the subjects don't fall asleep during the night.

      The following day, 24 hours after the resting baseline session, the fatigue baseline session
      will start. Sessions of resting baseline and fatigue baseline will be scheduled for the same
      time of day on two consecutive days to account for circadian alignment. The testing procedure
      will be identical to the resting baseline session that means subjects will drive for 60
      minutes on the driving simulator and perform the same cognitive tests as in the baseline
      session. After completion of the fatigue baseline session, the study drug (armodafinil 250 mg
      or placebo) will be administered. To determine the pharmacokinetics, blood samples will be
      obtained prior to drug dosing and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 10 hours post-dose
      through an intravenous catheter placed in the arm vein of the subjects. After study drug
      intake subjects will perform 5 sessions on the driving simulator consisting of 30-minute
      drives. The same battery of tests performed at baseline will be performed between the drives.
      The tested cognitive abilities play an important role during driving and the investigators
      will investigate to what extent sleep deprivation alters these abilities and how armodafinil
      is able to counter the deteriorating effects of sleep deprivation on these capabilities.
    

Intervention name(s): armodafinil; Placebo (for armodafinil)
Intervention type(s): Drug; Drug
Intervention description(s): Armodafinil 250 mg tablet single dose administration. Outcome measures: Driving simulator performance, Electroencephalogram activity, Area under the plasma concentration versus time curve (AUC), Motor Praxis Task, the Visual Object Learning Test, the Fractal-2-Back, the Abstract Matching, the Line Orientation Test, the Digit-Symbol Substitution Task, the Balloon Analog Risk Test, and the Psychomotor Vigilance Test; Placebo tablet single dose administration. Outcome measures: Driving simulator performance, Electroencephalogram activity, Motor Praxis Task, the Visual Object Learning Test, the Fractal-2-Back, the Abstract Matching, the Line Orientation Test, the Digit-Symbol Substitution Task, the Balloon Analog Risk Test, and the Psychomotor Vigilance Test
Other intervention name(s): Nuvigil
Intervention MeSH terms: Modafinil
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Basic Science