A single-centre, placebo-controlled, crossover study in healthy medical registrars to enable validation of the mini-neurocart with the laparoscopy box trainer

It is widely accepted that fatigue and sleep deprivation negatively affect
performance, varying from mood and cognitive function to motor performance.
This is a problem for surgical specialists as they commonly work long shifts,
perform under high pressure of making the right medical decisions, and are
dependent upon motor skills during surgical procedures.

As a consequence for the patient, doctor*s fatigue could lead to an increased
risk of surgical complications and negligence in care that could seriously
endanger its safety. As a consequence to the doctor, this leads to high rates
of stress and depression, somatic complaints, pregnancy-related problems, and
even an increased risk of vehicle accidents.

Not surprisingly, the public and professional awareness of the issue of fatigue
among doctors is increasing. However, what is to be considered *tired* and
oppositely *fit* in the context of the medical specialist remains to be
defined. Furthermore a relevant frame of reference of what can be considered
acceptable or not is lacking.

To overcome these shortcomings, this study is designed to comprehensively
explore the different aspects of fatigue of both surgical specialists and their
residents, to relate these aspects to the validated effects of drugs on which
legal limits have been set, and to define surgical fitness-to-perform.

The FTOP test is designed to target several CNS parameters of fitness that are
all professionally relevant, enabling formation of an objective scale to assess
the level of performance. Validation of these CNS scores with a laparoscopic
trainer is necessary in order to create a professional frame of reference. The
use of the ForMoST (Force Motion Surgical Trainer) box trainer, provides a
means to objectively classify the performance of surgeons according to their
laparoscopic skill.

Results from this study will provide the surgical specialist with a practical,
validated tool, to help deciding whether to operate or not. Ultimately, a Fit
to Perform test could limit performing under great tiredness, could increase
the quality of life of surgical specialists, and could improve patient safety.

This study has the primary aim to correlate subjective fitness of medical
specialists to objective scales and relate the scores to validated levels of
performance, which would be considered acceptable to perform surgical
procedures.

Objectives of this study using the Mini-NC and ForMoST box trainer in healthy
specialist registrars are as follows:

Primary Objective:
Validation of the Fit tot Perform test using a laparoscopic box trainer.

Secondary Objective:
To compare the anticipated decreased scores in the Fit to perform test to the
anticipated decrease in laparoscopy performance under the influence of ethanol.

This is a single-centre, placebo-controlled, crossover study with ethanol
clamping in healthy medical registrars while performing tests on the FTOP-test
and ForMoST box trainer. Subjects will function as their own control. The tests
will be conducted during one testing day. Subjects will perform the tests in
randomised order under administration of placebo and different levels of
ethanol. By comparing the changes in scores of both the Mini-NC and the
Laparoscopy-simulator, a correlation between the tests may be established and a
cut-off value based on legal alcohol limits as well as pre-set professional
laparoscopy requirements can be set. Taken together, these findings enable the
validation of the Mini-NC with the laparoscopy box trainer.
The total duration of the study for each subject will be up to 21 days divided
as follows:
* Screening: Up to 21 days before dosing;
* Treatment and study assessments: Day 1;
* In Clinic period: one day;
Subjects will be admitted to the Clinical Research Unit (CRU) and will be
discharged approximately 12 hours after study drug administration.

Ethanol intravenous administration:

Prior to a study occasion, the study statistician will prepare individual
computer spreadsheets, according to a randomized schedule. For alcohol
occasions, this spreadsheet contains a blank *measurement column*, in which the
measured BrEC-values (breath ethanol concentration) are entered by the infusion
assistant. Based on these results, the spreadsheet calculates the new infusion
rate.
1. The clamping procedure will be initiated to achieve a stable pseudo-steady
state level of 0.3 g·L-1; a spread sheet-based paradigm using BrEC guided
adjustments of infusion rates will be used to maintain stable levels.
2. Clamping procedure will be modified to achieve a stable pseudo-steady state
level of 0.6 g·L-1; a spread sheet-based paradigm using BrEC guided adjustments
of infusion rates will be used to maintain stable levels.

Placebo intravenous administration:

For placebo occasions, the spreadsheet contains a separate column with *sham*
BrEC-values, determined from kinetic simulations. At each protocol time, the
infusion assistant will enter the corresponding *sham* value into the
measurement column. This value will be used by the spreadsheet to calculate a
new *sham* infusion rate, which can be applied accordingly. In this manner,
operations during the alcohol clamping and sham procedures are exactly similar
for the subject. At measuring times identical to the clamping procedure,
subjects will perform tests on the ForMoST laparoscopy box trainer and
FTOP-test.

Depending on randomization, subjects in this study can be subjected to placebo
or the depressant ethanol.

The nature of the study requires subjects to be present at the CHDR for a total
of one day; this may interfere with the normal work schedule of these
registrars. Participating subjects will be financially compensated.