Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623001319662
Ethics application status
Approved
Date submitted
21/05/2023
Date registered
15/12/2023
Date last updated
15/12/2023
Date data sharing statement initially provided
15/12/2023
Date results information initially provided
15/12/2023
Type of registration
Retrospectively registered

Titles & IDs
Public title
Measuring the effects of hypoxia training on diver performance
Scientific title
Implications of a prior training exposure on recognition of cognitive and physiological symptoms during a later hypoxic exposure in divers
Secondary ID [1] 309675 0
None
Universal Trial Number (UTN)
U1111-1266-1320
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
hypoxia 330033 0
Condition category
Condition code
Anaesthesiology 326939 326939 0 0
Other anaesthesiology
Neurological 326941 326941 0 0
Studies of the normal brain and nervous system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study will take place in-person at the Exercise Metabolism Laboratory at the University of Auckland.

A two-part, randomized, single blind study will be conducted. There are two trial arms requiring 20 participants each (n = 40). Unblinded participants will be randomized 1:1 to the hypoxia exposure or no exposure arms. At a later date, blinded participants from both groups will be exposed to a “test event” involving exposure to hypoxia and asked to perform a simulated self-rescue task if hypoxic symptoms are perceived.

Objective: Examine the role of a prior hypoxic exposure on symptom recognition and self-rescue during a second, later hypoxic exposure.

Hypoxia exposure arm:
Participants (n = 20) randomized to hypoxia exposure will participate in a single, individual, open-label hypoxia exposure session of 1 hours duration. A commercially available rebreather will be used. The oxygen controller will be set to maintain a partial pressure of inspired oxygen at 0.21 atmospheres (equivalent to room air). At the appropriate time in the experimental protocol the oxygen supply will be switched off to mimic a gradual change into hypoxia that can occur in diving. For example, this mimics the unfortunately common scenario where a diver enters the water breathing air, then initiates a dive after forgetting to switch on the oxygen supply to their rebreather. As several liters of breathable gas remain in the rebreather circuit, it takes several minutes for the diver to metabolize the oxygen content of this residual gas. This leads to a gradual change into hypoxia that will be mimicked in our protocol.

Participants will be performing a card recognition task, similar to those regularly conducted during commercial and military aviation hypoxia awareness training. Participants will be asked to verbalize the number and suit of the card within four seconds, when a new card will appear. Participants will be familiarized with the test under normoxic conditions to confirm 100% accuracy and test re-test reliability.

Participants will be seated and instrumented with a 3-lead electrocardiogram and finger pulse oximeter. End tidal PCO2 (ETCO2) and inspired PO2 and PCO2 will be continuously measured by sampling from the breathing circuit throughout the exposure. A portable EEG system will be applied. A functional near infrared spectroscopy (fNIRS) system will be combined with the EEG electrodes using an EEG-compatible fNIRS cap. A non-invasive blood pressure finger cuff will be used to continuously measure beat-to-beat blood pressure. In those participants who separately consent, an arterial cannula will be placed in the radial artery of the non-dominant wrist. An arterial blood gas sample will be taken at the start of the baseline card-recognition task. An additional blood gas sample will be taken when the hypoxic exposure is terminated. The drawing of each blood sample will not interfere with the participant’s ability to carry out the card-recognition task. All arterial blood gas samples will be run through a portable iSTAT arterial blood gas analyser which will be in the laboratory during the experiment. This will provide immediate results of PaO2, PaCO2 and oxygen saturation for all blood samples. The arterial line and blood sample collection will be performed by an anaesthetic registrar or consultant anaesthetist.

The session will begin with the participant breathing from the rebreather loop with a constant oxygen concentration and performing a two-minute baseline card-recognition task. The oxygen supply will then be switched off to create a hypoxic mixture. The exposure will be terminated on committal of the second card recognition error after the peripheral oxygen saturation falls below 60%. Alternatively (for safety reasons) the exposure will be terminated if the participant commits three errors prior to reaching a peripheral oxygen saturation of 60%.

Five minutes after the exposure, the participant will be asked to recall the total number of errors he or she made and to rate the severity of potential hypoxia symptoms on a visual analogue scale.

Test event:
The "test event" will take place approximately five weeks after the initial hypoxic exposure. Participants in both original groups (no exposure versus hypoxic exposure) will be exposed to the hypoxia test event. Participants will be informed that there is a 50% chance of being randomized to breathe hypoxic gas, and a 50% chance of being randomized to breathe air, however, participants will also be informed that their allocations will be concealed until after the final measurement to avoid expectation bias. The research team will debrief all participants and reveal their allocations prior to concluding the study.

The set-up will be similar to that of the initial hypoxia exposure, including the use of EEG and fNIRS. Additionally, a virtual reality headset with embedded eye tracking technology will be employed. Participants will view a video of an underwater swim and will be asked to perform a virtual fish survey, similar to a scientific diving objective, to identify a specific fish species and to count these fish in a realistic and immersive underwater environment. This is intentionally a different cognitive task to that undertaken by those experiencing the initial hypoxia exposure in the first allocation to avoid confounding due to practice effect.
Prior to beginning the event, participants will be instructed to perform "self-rescue" if any impairment is perceived. Self-rescue will involve operation of the mouth-piece bailout valve; a task which involves both hands and a certain degree of manual dexterity.

Participants will be allowed to become immersed in the task, after which they will either be switched to hypoxic gas breathing or continue breathing a normoxic gas. Participants will be videoed, and accuracy of the distractor task and time to self-rescue initiation after the switch to hypoxic gas breathing will be recorded. If a participant ceases recording fish counts or reaches a peripheral oxygen saturation of less than 60% without bailing out, the participant will be prompted to bail-out with a visual stimulus inside the VR environment, if no response occurs the event will be terminated. Five minutes after the exposure, participants will be asked to rate the severity of potential hypoxia symptoms on a visual analog scale.

Both the initial hypoxia exposure and the later test event are recorded on video using two cameras. One records the participant and their interaction with the distractor task (card recognition or simulated dive), while the other records the entire experimental setup and the actions of the investigators. Fidelity to the planned intervention will be assessed by auditing the recordings for errors.
Intervention code [1] 326120 0
Diagnosis / Prognosis
Comparator / control treatment
No exposure arm (Hypoxia):
Participants (n = 20) randomized to no exposure will receive a letter revealing their allocation. The letter will also contain a description of the symptoms of hypoxia presented in a manner that reflects commonly available diver education material.
Control group
Active

Outcomes
Primary outcome [1] 334782 0
Time to self-rescue after initiation of hypoxic gas breathing as measured using an electronic timer.
Timepoint [1] 334782 0
5 weeks after initial intervention (hypoxia exposure for the intervention group, or receipt of information leaflet by the control group).
Primary outcome [2] 334783 0
Number of participants who self-rescue as assessed by direct observation of a successful bailout.
Timepoint [2] 334783 0
5 weeks after initial intervention (hypoxia exposure for the intervention group, or receipt of information leaflet by the control group).
Secondary outcome [1] 429144 0
Time to self-rescue after switch to hypoxic breathing gas.
Timepoint [1] 429144 0
5 weeks after initial intervention (hypoxia exposure for the intervention group, or receipt of information leaflet by the control group).

Eligibility
Key inclusion criteria
To be eligible, a prospective participant must meet all of the following:
• Age within the range of 18 to 55 years old
• Ability to read, write, and understand English
• Binocular acuity that is normal either corrected or uncorrected
• Possession of a valid scuba diving certification
• Medical fitness for diving according to Recreational Scuba Training Council recreational diver standards
• Provide written informed consent
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
A prospective participant will be ineligible to participate if any of the following are met:
• Current use of recreational drugs
• Current use of psychoactive medications including antihistamines
• History of mental illness
• Excessive use of alcohol (more than 21 standard alcoholic drinks per week)
• Consumption of over five glasses per day of caffeine-containing beverages (or its equivalent if taken as another form)
• Current smoker
• Previously participated in a hypoxia study.

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomization using a randomization table created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
It is effectively impossible to calculate power for a study of this nature where neither a typical capacity for self-rescue nor the potential learning benefit of an initial hypoxia exposure are defined. However, if (for example) one assumes a peripheral oxygen saturation of 65% represents a notional point of no return for initiation of self-rescue in the test exposure, then based on the data from our earlier study using the same hypoxia protocol, a self-rescue initiated 30% earlier (in time) would see it occur at a much safer peripheral oxygen saturation of 85%. A sample of 12 subjects in each group would be required to demonstrate a reduction in time to self-rescue of this magnitude (a 0.05, ß 0.2, power 0.8). We plan for 20 per group. We acknowledge that all of this is highly speculative and that awareness of hypoxic symptoms in distracted and task-loaded subjects, and the effect of prior hypoxic exposure on this awareness is a complete unknown (and part of the reason for performing the study). With that said, unless there is a moderately large effect detectable (even as a strong indicative trend that could be further investigated) by a study of this size in which the blinded test event occurs less than two after the open label exposure, it would be hard to make a case that widespread hypoxia training for rebreather divers should be promoted, and current practices with aircrew could also be questioned.

Demographics and baseline data (e.g. age, weight, sex, years of scuba experience) will be described with descriptive statistics.

Depending on the outcomes (which are difficult to anticipate) it may also be possible to use the proportion of subjects who initiate self-rescue before the safety termination criterion (see prior) is met versus those who do not as an outcome comparator between these groups.

Records of all monitoring modalities will be time-aligned so that neurophysiological changes in EEG and fNIRS can be correlated against changes in other relevant physiological parameters such as SPO2, ETCO2, minute volume, any cognitive dysfunction indicated by the card recognition test, and time to termination due to symptoms.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
1/05/2023
Date of last participant enrolment
Anticipated
Actual
5/12/2023
Date of last data collection
Anticipated
9/01/2024
Actual
Sample size
Target
40
Accrual to date
Final
40
Recruitment outside Australia
Country [1] 25547 0
New Zealand
State/province [1] 25547 0

Funding & Sponsors
Funding source category [1] 313867 0
Government body
Name [1] 313867 0
Office of Naval Research, United States Navy
Country [1] 313867 0
United States of America
Primary sponsor type
University
Name
University of Auckland
Address
Department of Anaesthesiology,University of Auckland.30 Park AvenueGrafton, Auckland 1023
Country
New Zealand
Secondary sponsor category [1] 315708 0
None
Name [1] 315708 0
Address [1] 315708 0
Country [1] 315708 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313016 0
Northern B Health and Disability Ethics Committee
Ethics committee address [1] 313016 0
Ministry of HealthFreyberg Building20 Aitken StreetPO Box 5013Wellington 6011
Ethics committee country [1] 313016 0
New Zealand
Date submitted for ethics approval [1] 313016 0
Approval date [1] 313016 0
03/05/2021
Ethics approval number [1] 313016 0
21/NTB/102

Summary
Brief summary
“Rebreather” underwater breathing devices allow divers to recycle the gas that they breathe out by removing carbon dioxide and adding oxygen. Divers using rebreathers may be at risk of experiencing hypoxia (low oxygen levels) which affect how they think and act, and can lead to accidents or injury. All divers that use rebreathers have learned about the dangers of hypoxia. In this study we will look at whether you may be able to better recognize hypoxia during a simulated (or pretend) dry dive if you first experience hypoxia in a controlled “training” session.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 126690 0
Prof Simon Mitchell
Address 126690 0
Department of Anaesthesiology,University of Auckland.30 Park AvenueGrafton, Auckland 1023
Country 126690 0
New Zealand
Phone 126690 0
+64 9 923 9300
Fax 126690 0
Email 126690 0
sj.mitchell@auckland.ac.nz
Contact person for public queries
Name 126691 0
Dr Xavier Vrijdag
Address 126691 0
Department of Anaesthesiology,University of Auckland.30 Park AvenueGrafton, Auckland 1023
Country 126691 0
New Zealand
Phone 126691 0
+64 9 923 9300
Fax 126691 0
Email 126691 0
x.vrijdag@auckland.ac.nz
Contact person for scientific queries
Name 126692 0
Dr Xavier Vrijdag
Address 126692 0
Department of Anaesthesiology,University of Auckland.30 Park AvenueGrafton, Auckland 1023
Country 126692 0
New Zealand
Phone 126692 0
+64 9 923 9300
Fax 126692 0
Email 126692 0
x.vrijdag@auckland.ac.nz

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
Vital sign recordings
Breathing gas analysis
Arterial blood gas data
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 (sj.mitchell@auckland.ac.nz)


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.