Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001049763
Ethics application status
Approved
Date submitted
15/07/2022
Date registered
28/07/2022
Date last updated
23/06/2024
Date data sharing statement initially provided
28/07/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Measuring the effects of inert gas narcosis in divers with electroencephalogram (EEG)
Scientific title
Monitoring inert gas narcosis in hyperbaric environments
Secondary ID [1] 307580 0
None
Universal Trial Number (UTN)
U1111-1264-2010
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
gas narcosis 327029 0
Condition category
Condition code
Anaesthesiology 324200 324200 0 0
Other anaesthesiology
Neurological 324201 324201 0 0
Studies of the normal brain and nervous system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
In this prospective intervention study a total of 24 participants are needed. There are two parts in this study each requiring 12 participants.

Objective 1 – To refine the novel mutual information qEEG algorithm for nitrogen narcosis by exposing subject to a wider range of nitrogen dose
In the first experiment, we will recruit 12 participants to attend one session at the hyperbaric chamber, in which they will be exposed to a pressure of 8 atmospheres absolute (ATA) while breathing air. After checking participant eligibility for testing on the day, psychometric test familiarisation will be conducted. The EEG electrode cap will be placed and checked for electrode impedance. Each measurement will consist of one-minute EEG recording with eyes open and one-minute EEG recording with eyes closed. The psychometric tests will then be administered and EEG recordings subsequently repeated. The EEG will also be recorded during the psychometric test administration.

At surface pressure, baseline measurements (as above) will be taken inside the hyperbaric chamber. Directly after, the chamber will be pressurised to 8 ATA at a rate of 1 ATA per minute maximum to minimise heat built-up that could cause sweating, which impairs EEG signal quality. At 8 ATA, the measurements will be repeated after five minutes acclimatisation to air-breathing at that pressure. The decompression will be controlled (including oxygen stops) according to the schedule prescribed by the Canadian Navy decompression tables.

In our previous research effort, we exposed participants to a maximum of 6 ATA and found subtle effects of impairment. With this new exposure to 8 ATA, we expect to record a stronger narcotic effect, which will allow us to associate the subtle EEG changes with narcosis more confidently.

Objective 2 – To benchmark the real-time mutual information algorithm with nitrogen narcosis in a wider group of subjects and with a more sensitive cognitive function test
For the second experiment, we will recruit another 12 participants to attend a session at the hyperbaric chamber, in which each participant will be exposed to a pressure of six ATA while breathing air. In a similar approach to that described above, the session will consist of preparation, followed by baseline and depth EEG measurements.

At surface pressure, baseline measurements (as above) will be taken inside the hyperbaric chamber. Directly after, the chamber will be pressurised to 6 ATA at a rate of 1 ATA per minute maximum to minimise heat built-up that could cause sweating, which impairs EEG signal quality. At 6 ATA, the measurements will be repeated after five minutes acclimatisation to air-breathing at that pressure. The decompression will be controlled (including oxygen stops) according to the schedule prescribed by the Canadian Navy decompression tables.

This will provide an extension of the current database of EEG recordings we collected from participants exposed to 6 ATA in our previous approved study, which will allow us to assess the metric's performance with new participants and (combined with previous data) better characterise sensitivity, specificity, and positive predictive value for manifestations of cognitive impairment. The psychometric task will be used to identify impairment levels that can be considered to increase danger to the diver, and we will correlate those changes against the mutual information EEG changes. A parallel aim of conducting this work is to minimise the number of electrodes required to apply the mutual information algorithm with a view to eventual real-world use. This will be a post-hoc analysis.
Intervention code [1] 324032 0
Diagnosis / Prognosis
Comparator / control treatment
The measurement before exposure to the specific breathing gas will be used as a control measurement.
Control group
Active

Outcomes
Primary outcome [1] 332017 0
relative change in narcosis depth measured with a developed quantitative EEG measurement composite of both mutual information and global efficiency (functional connectivity analysis)
Timepoint [1] 332017 0
baseline (before exposure) and for the duration of 10 minutes during exposure to the breathing gas mixture.
Secondary outcome [1] 411910 0
relative change in higher cognitive functions, measured with a psychometric test.

The Serial Sevens (S77) measures effect on comprehension of the information processing of the brain. Because both are higher cognitive functions they are more affected by gas narcosis. The tests will be performed on a specifically programmed dive computer. The test administration program stores the reaction time and errors made of each test for analysis. Baseline measurements will be regarded as 100% functioning. Subsequent measurements will be compared to this baseline measurement.
Timepoint [1] 411910 0
baseline (before exposure) and for the duration of 5 minutes during exposure to the breathing gas gas mixture.

Eligibility
Key inclusion criteria
• Age between 18 and 55 years old
• Written informed consent
• Normal static binocular acuity, corrected or uncorrected
• Normal hearing
• Basic fluency in the English language
• Possession of a valid technical diving certificate
• Medical fitness for diving according to Recreational Scuba Training Council (RSTC) recreational diver standards.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
A potential subject who meets any of the following criteria will be excluded from participation in this study:
• Current recreational drug use
• Use of psychoactive medication, including anti-histamines
• Mental illness
• Excessive alcohol use (>21 standard alcoholic drinks per week)
• Intake of caffeine-containing beverages over five glasses per day
• Smoker

After inclusion, a participant will be withdrawn from the study if:
• There is a deviation of the research protocol by the participant
• There is an intake of non-permitted medication
• There is an intake of alcohol 24 hours before the test
• There is an intake of caffeine-containing beverages during the test days
• Less than 6 hours of sleep during the night prior to the test day
• A dive made within 24 hours prior to an experiment involving hyperbaric exposure
• There are signs or symptoms of decompression illness
• They request to be withdrawn

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
For each of the two parts of the study, the participants are in a pre- and post-exposure designed study.
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis
Sample size calculation
Based on previous studies and our previous work (Vrijdag et al., 2021), we will need 12 participants in each group to detect differences between the hyperbaric exposure and the baseline measurement. Two studies utilising EEG measurements while breathing air (Bevan, 1971; Pastena et al., 2005) demonstrated differences in the EEG patterns with 10 and 13 participants, respectively. Studies showing differences in functioning while breathing nitrogen and oxygen in a hyperbaric chamber (Frankenhaeuser, Graff-Lonnevig and Hesser, 1963) utilised 12 participants.

EEG analysis
The scores calculated with thedeveloped qEEG algorithm will be correlated to the percentage of functioning on the psychometric test. If each level of nitrogen exposure shows a high correlation with the qEEG value and functioning on the psychometric tests, the qEEG will be regarded as sensitive for nitrogen narcosis.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/11/2022
Actual
1/11/2022
Date of last participant enrolment
Anticipated
31/12/2024
Actual
Date of last data collection
Anticipated
31/12/2024
Actual
Sample size
Target
24
Accrual to date
12
Final
Recruitment outside Australia
Country [1] 24895 0
New Zealand
State/province [1] 24895 0
Auckland

Funding & Sponsors
Funding source category [1] 311851 0
Government body
Name [1] 311851 0
Office of Naval Research, US Navy
Country [1] 311851 0
United States of America
Primary sponsor type
University
Name
University of Auckland
Address
Department of Anaesthesiology,
University of Auckland.
30 Park Avenue
Grafton, Auckland 1023
Country
New Zealand
Secondary sponsor category [1] 313326 0
None
Name [1] 313326 0
Address [1] 313326 0
Country [1] 313326 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311291 0
Northern B Health and Disability Ethics Committee
Ethics committee address [1] 311291 0
Ethics committee country [1] 311291 0
New Zealand
Date submitted for ethics approval [1] 311291 0
19/02/2021
Approval date [1] 311291 0
29/03/2021
Ethics approval number [1] 311291 0
21/NTB/51

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 120594 0
Prof Simon Mitchell
Address 120594 0
Department of Anaesthesiology,
University of Auckland.
30 Park Avenue
Grafton, Auckland 1023
Country 120594 0
New Zealand
Phone 120594 0
+64 9 923 9300
Fax 120594 0
Email 120594 0
[email protected]
Contact person for public queries
Name 120595 0
Xavier Vrijdag
Address 120595 0
Department of Anaesthesiology,
University of Auckland.
30 Park Avenue
Grafton, Auckland 1023
Country 120595 0
New Zealand
Phone 120595 0
+64 9 923 9300
Fax 120595 0
Email 120595 0
[email protected]
Contact person for scientific queries
Name 120596 0
Xavier Vrijdag
Address 120596 0
Department of Anaesthesiology,
University of Auckland.
30 Park Avenue
Grafton, Auckland 1023
Country 120596 0
New Zealand
Phone 120596 0
+64 9 923 9300
Fax 120596 0
Email 120596 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Basic demographics
Psychometric test results
EEG recordings
When will data be available (start and end dates)?
6 months after publication of main results
no end date determined
Available to whom?
researchers who provide a methodologically sound proposal at the discretion of Primary Sponsor
Available for what types of analyses?
to achieve the aims in the approved proposal and for meta-analyses
How or where can data be obtained?
access subject to approvals by Principal Investigator ([email protected])


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.