ObjectivesPrimary:• To assess the effect of ethanol compared to placebo on a driving simulator performance tests;• To assess the effect of alprazolam compared to placebo on a driving simulator performance tests;Secondary:• To assess the effect of…
ID
Source
Brief title
Condition
- Other condition
- Environmental issues
Synonym
Health condition
safety
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
NeuroCart assessment:
1.Adaptive tracking (average performance %);
2.Saccadic eye movements (saccadic reaction time (sec), saccadic peak velocity
(deg/sec), and saccadic inaccuracy (%));
3.Smooth pursuit eye movements (percentage of the time that subject*s eyes are
in smooth pursuit of the target (%));
4.Body sway (antero-posterior sway (mm/2min));
5.Visual verbal learning test (VVLT)
6.Visual Analogue Scales according to Bond and Lader (alertness, mood, and
calmness subscales (mm)).
7. Stop signal task (mean response time on GO-trials, total correct responses
on Go-trials, total missed responses on Go-trials, mean response time on
Stop-trials, total correct responses on Stop-trials, mean stop signal delay
(SSD) of the Stop-trials and stop signal response time)
Driving simulator assessment:
1. Standard deviation of Lateral Position (SDLP in centimeters)
Questionnaire driving behaviour and safety:
1. driving behaviour questionnaire
Secondary outcome
Parameters to detect drug effects
1. Useful Field Of View test (UFOV)
2. Lapses of inattention
3. Standard deviation of speed
4. Mean Speed
5. Mean lateral position
6. Simple reaction time
7. Spatial perceptual-task
8. Standard deviation of throttle position
9. Steering wheel test
Safety driving performance parameters
1. Keeping safe distance
2. Car following
3. Driving failures
4. Gap acceptance
5. Drive safety score (DSS)
6. Reaction to unexpected events
7. Traffic violations
a. Traffic light scenario
Background summary
Pharmacological agents can induce fatigue and reduce vigilance leading to
periods of inattention and as such poses a risk factor for usage during daily
activities, especially in driving. Therefore it is important to determine
whether the ability to drive a motorized vehicle is affected by a
pharmaceutical agent.
Currently the ability to drive is assessed by using a standardized method, the
Dutch on-the-road driving test (O*Hanlon, 1982). This test method has been used
extensively to assess the sedative effects of numerous pharmacological
substances (Verster, 201; O*Hanlon, 1982). During this test subjects are
instructed to drive with a steady lateral position and constant speed on a
public highway in normal traffic conditions and under supervision of a skilled
instructor and continuous camera registration.
However some drugs are known to possess psycho-stimulant properties and drugs
of abuse are known to lead to inactive, impatient or erratic behaviour, which
poses risks for driving that are more difficult to assess under real driving
circumstances. New medicines in general carry a larger risk for such unexpected
behavioural effects but increasingly, knowledge about the effects of such
medicines on risky daily activities is important early in development.
Therefore, a public on-the-road test may not be the most suitable to measure
drug-induced driving risks.
The purpose of the study is to determine the sensitivity of a driving simulator
test battery to the effects of ethanol 0.5 and 1.0 g/L and alprazolam 1 mg, and
to explore the relationships with historical results from actual driving
performance. In addition, the results will also be compared with those of the
NeuroCart, a validated test battery that quantifies a large range of
drug-sensitive CNS-functions that are also relevant for every-day performance.
Results from this study will allow us to determine whether a driving simulator
is suitable to assess impairment in performance due to pharmacological agents
in a laboratory setting.
Study objective
Objectives
Primary:
• To assess the effect of ethanol compared to placebo on a driving simulator
performance tests;
• To assess the effect of alprazolam compared to placebo on a driving simulator
performance tests;
Secondary:
• To assess the effect of alprazolam compared to ethanol on driving simulator
performance tests;
• To establish the relationship between driving simulator and NeuroCart
performances;
• To study the suitability of additional complex parameters of driving
simulation on the assessment of drug effects.
• To explore the relationships between driving simulator and historical results
from actual driving performance.
Study design
This is a single-centre, randomized, double-blind, double-dummy,
placebo-controlled, four-way crossover study with ethanol 0.5 and 1.0 g/L and
alprazolam 1 mg in 24 healthy subjects while performing neurocognitive and
psychomotor tests on the NeuroCart and driving simulator.
Intervention
During the four occasions study subjects receive the following treatments in
randomized order:
• Alprazolam 1 mg + placebo (sham clamp)
• Placebo (capsule) + ethanol clamping (0.5 g/L)
• Placebo (capsule) + ethanol clamping (1.0 g/L)
• Placebo (capsule) + placebo (sham clamp)
Study burden and risks
No exceptional severe adverse drug reactions are expected and
burden/convenience for the subjects are considered relatively mild.
Side-effects alprazolam: - expected: daytime drowsiness, dizziness, muscle
weakness, and ataxia. Side-effects ethanol clampling: -expected: sleepiness,
headache, dizziness and drunken feeling. Placement of the cannula can be
painful and sometimes causes bruizing, also the site of infusion can be painful
during the start of dosing, preventative action is taken in the form of
simultaneous glucose infusion.
Subjects have to perform an active task during the measurements. However,
subjects get sufficient rest during the measurements. Therefore, the
measurements will cost little effort. The risk of the measurements is
minimally. Safety is performed by software and hardware of the devices.
Zernikedreef 8
Leiden 2333CL
NL
Zernikedreef 8
Leiden 2333CL
NL
Listed location countries
Age
Inclusion criteria
Eligible subjects must meet all of the following inclusion criteria:
1. Healthy subjects, aged 18 to 55 years, inclusive; healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including 12-lead ECG, and clinical laboratory tests.
2. Subjects are in possession of a valid driver*s license and are active and experienced drivers; this is to be determined by the investigators;
3. Evidence of a personally signed and dated informed consent form indicating that the study subject has been informed of all pertinent aspects of the study.
4. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other procedures.
5. Experienced alcoholic drinkers, with occasional well-tolerated self-exposure to eight alcohol-containing drinks per social occasion.
6. Female subjects of childbearing potential must have a negative (β-hCG) test (at screening and before the start of each occasion) and be willing and able to use one of the following double-barrier methods of birth control: hormonal intrauterine device with condom, or oral contraceptives with condom from the screening visit to the end of study
Exclusion criteria
Eligible subjects must meet none of the following exclusion criteria:
1. Confirmed or suspected myasthenia gravis, severe respiratory insufficiency, sleep apnoea syndrome, severe hepatic insufficiency or hypersensitivity to benzodiazepines;
2. Evidence or history of clinically significant haematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).
3. Any condition possibly affecting drug absorption (e.g., gastrectomy).
4. A positive urine drug screen for cocaine, amphetamine, morphine, benzodiazepine and THC.
5. Subject is not able to perform the drive simulator tests.
6. Treatment with an investigational drug within 3 months prior to screening or having participated in more than 4 investigational drug studies within 1 year prior to screening.
7. Use of (non-)prescription medications that are believed to affect subject safety or the overall results of the study following judgment by the investigator.
8. Loss or donation of blood over 500 mL within three months (males) or four months (females) prior to screening.
9. Unwilling or unable to comply with the Lifestyle Guidelines described in this protocol.
10. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
11. Subjects who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or subjects directly involved in the conduct of the study.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-003956-30-NL |
| CCMO | NL50821.056.14 |