Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623001275651
Ethics application status
Approved
Date submitted
23/11/2023
Date registered
7/12/2023
Date last updated
7/12/2023
Date data sharing statement initially provided
7/12/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Measuring the effects of hypercapnia on diver performance
Scientific title
Implications of a prior training exposure on recognition of cognitive and physiological symptoms during a later hypercapnic exposure in divers
Secondary ID [1] 311011 0
None
Universal Trial Number (UTN)
U1111-1266-1320
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypercapnia 332122 0
Condition category
Condition code
Anaesthesiology 328850 328850 0 0
Other anaesthesiology
Neurological 328851 328851 0 0
Studies of the normal brain and nervous system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study will be conducted at the Exercise Metabolism Laboratory at the University of Auckland.

Participants (n = 20) randomized to no exposure (normocapnia) will receive a letter revealing their allocation. The letter will also contain a description of the symptoms of hypercapnia presented in a manner that reflects treatment of the participant in commonly available diver education material.

Participants (n = 20) randomized to hypercapnia exposure will participate in an open-label hypercapnia exposure session. Participants will be directly observed by the research staff at all times when present for measurements to ensure adherence to study protocol. This will entail rebreathing of CO2 on a rebreather with no CO2 absorbent in the dedicated canister while performing a card recognition task. A commercially-available rebreather with a 100% O2 and air diluent cylinder will be used. The oxygen controller will be set to maintain a partial pressure of inspired oxygen at 0.7 atmospheres (71 kilopascals). A disposable anaesthetic circuit antimicrobial filter will be incorporated in the rebreather mouthpiece to mask changes in the circuit breathing resistance associated with the absence of CO2 absorbent and for sanitation purposes. Participants will be seated and will be instrumented with a 3-lead electrocardiogram, finger pulse oximeter and non-invasive finger cuff. A gas sampling line for continuous monitoring of inspired PO2 and ETCO2 will be attached to the mouthpiece filter port, and a pneumotachometer will be incorporated in the exhale limb for tidal volume, respiration rate, and minute volume measurements. 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.

The session will begin with the participant breathing air through the rebreather mouthpiece in an open-circuit configuration while performing a two-minute baseline card-recognition task. The rebreather circuit will then be switched to a closed-circuit configuration. Subsequently, the card recognition test will commence. The hypercapnia exposure termination criterion includes an ETCO2 of 8.5 kPa (65 mm Hg) or participant self-termination due to symptoms. Errors made on the card recognition test will be recorded, but committal of errors will not be a termination criterion because self-termination due to symptoms, or reaching an ETCO2 of 8.5 kPa provide very safe end points for the exposure.

Five minutes after the exposure, participants will be asked to recall the total number of errors they made and to rate the severity of potential hypercapnia symptoms on a VAS.

The "test event" will take place approximately five weeks after the initial hypercapnic exposure. Participants in both original groups (no exposure (normocapnia) versus hypercapnia exposure) will participate in a second single-blind hypercapnia exposure.

During the hypercapnic test event, participants will breathe from a rebreather with no functioning CO2 scrubber. Monitoring will be as described for the hypercapnic training event described above. 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 hypercapnia exposure in the first allocation to avoid confounding due to practice effect.

Participants will be asked to perform the fish counting task described above while exercising on a cycle ergometer, at approximately 110 watts of work; roughly equivalent to a diver finning at 0.5 to 1 knot. We have recently validated the use of the virtual reality oculography technique during ergometer cycling, as head mounted eye-tracking during exercise is novel.

Participants will be instructed to perform a self-rescue task if hypercapnic symptoms are 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 videoed, and accuracy of the distractor task and time to self-rescue initiation will be collected. We will also correlate these variables with end tidal CO2 levels. The primary outcome will be based on comparing these outcomes in participants allocated to no exposure (normocapnia) versus hypercapnia in the first allocation.

For safety, if a participant allocated to a hypercapnia event ceases recording fish counts or reaches an end tidal CO2 of 8.5 kPa without bailing out, the participant will receive a visual stimulus to bail-out, and if not followed the event will be terminated. Five minutes after the exposure, participants will be asked to rate the severity of potential hypercapnia symptoms on a VAS.
Intervention code [1] 327460 0
Diagnosis / Prognosis
Comparator / control treatment
No exposure arm (Hypercapnia):
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 hypercapnia presented in a manner that reflects commonly available diver education material
Control group
Active

Outcomes
Primary outcome [1] 336653 0
Number of participants who self-rescue as assessed by direct observation of a successful bailout.
Timepoint [1] 336653 0
5 weeks after initial intervention (hypoxia exposure for the intervention group, or receipt of information leaflet by the control group).
Secondary outcome [1] 429189 0
Time to self-rescue after initiation of hypercapnic gas breathing
Timepoint [1] 429189 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 hypercapnia 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 hypercapnic exposure are defined. We have conducted a previous study of hypoxia exposure using a similar methodology and found that 40 participants randomized to two groups of 20 yielded sufficient power for analysis. Assuming a similar effect size for hypercapnia, we have chosen to recruit 40 participants for this study as well.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
8/01/2024
Actual
Date of last participant enrolment
Anticipated
31/05/2024
Actual
Date of last data collection
Anticipated
31/12/2024
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment outside Australia
Country [1] 25984 0
New Zealand
State/province [1] 25984 0

Funding & Sponsors
Funding source category [1] 315275 0
Government body
Name [1] 315275 0
Office of Naval Research, United States Navy
Country [1] 315275 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] 317310 0
None
Name [1] 317310 0
Address [1] 317310 0
Country [1] 317310 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314194 0
Northern B Health and Disability Ethics Committee
Ethics committee address [1] 314194 0
Ethics committee country [1] 314194 0
New Zealand
Date submitted for ethics approval [1] 314194 0
Approval date [1] 314194 0
03/05/2021
Ethics approval number [1] 314194 0
21/NTB/102

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

Contacts
Principal investigator
Name 130746 0
Prof Simon Mitchell
Address 130746 0
Department of Anaesthesiology,University of Auckland.30 Park AvenueGrafton, Auckland 1023
Country 130746 0
New Zealand
Phone 130746 0
+64 9 923 9300
Fax 130746 0
Email 130746 0
[email protected]
Contact person for public queries
Name 130747 0
Xavier Vrijdag
Address 130747 0
Department of Anaesthesiology,University of Auckland.30 Park AvenueGrafton, Auckland 1023
Country 130747 0
New Zealand
Phone 130747 0
+64 9 923 9300
Fax 130747 0
Email 130747 0
[email protected]
Contact person for scientific queries
Name 130748 0
Xavier Vrijdag
Address 130748 0
Department of Anaesthesiology,University of Auckland.30 Park AvenueGrafton, Auckland 1023
Country 130748 0
New Zealand
Phone 130748 0
+64 9 923 9300
Fax 130748 0
Email 130748 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
Vital sign recordings
Breathing gas analysis
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.