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Trial registered on ANZCTR


Registration number
ACTRN12620000691943p
Ethics application status
Submitted, not yet approved
Date submitted
17/03/2020
Date registered
22/06/2020
Date last updated
22/06/2020
Date data sharing statement initially provided
22/06/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Comparing standard blood oxygen measures to a new device in humans under changing oxygen conditions
Scientific title
The validation of human cerebral oxygenation sensitivity and reproducibility of a novel MR-based device under dynamic conditions in healthy humans
Secondary ID [1] 300813 0
Nil
Universal Trial Number (UTN)
U1111-1249-8937
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Stroke 316693 0
Global Hypoxia 316694 0
Cardiac Bypass Related Embolism 316695 0
Global Ischemia 316696 0
Condition category
Condition code
Neurological 314939 314939 0 0
Other neurological disorders
Stroke 315131 315131 0 0
Haemorrhagic
Stroke 315132 315132 0 0
Ischaemic
Cardiovascular 315133 315133 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a single-arm, non-crossover study, in which participants will act as their own control within a single testing phase via the collection of baseline data.

This protocol will involve rebreathing a predetermined gas mixture that matches the participants personal end-tidal gasses to induce cyclical reductions or increases in body/brain oxygenation. Studies will take place at the Centre of Translational Physiology, University of Otago Wellington. The study will last roughly 90 minutes, if not otherwise ceased. This study uses a baseline recording as a control and so only one trial is required. A researcher will also be present with the participant for the duration of the study.

Participants will also be asked to change into an Equivital vest for non-invasive monitoring of vital signs (ECG, breathing rate, temperature). They will be instrumented with a 23 gauge butterfly needle catheter in either the left or right Median Cubital Vein for intermittent blood draws, which will be used for intermittent blood gas analysis (a total of 9mL over 90 minutes). This will be performed by a medical doctor.

Participants will then be instrumented with a plastic nasal gas sampling line, and asked to relax for three minutes to ascertain their average end-tidal respiratory gasses. This instrumentation will be performed by a researcher. This average measurement of their end-tidal gasses will be used to fill the Douglas bag.

Full instrumentation with (i) a plastic face mask with gas sampling line; (ii) a finger SpO2 clip; and a (iii) finger blood pressure cuff will then be performed by a researcher. The participant will lie supine on a clinic bed with their head in the cavity of our device. Their head will be lightly restrained to limit movement. All of these readings are continuous. Intermittent blood draws (1mL) at the start and end of each phase will be performed by a medical doctor.

A baseline recording under normal atmospheric conditions will take 7 minutes; this will act as our control. The first blood draw will then occur. The first rebreathing phase will then start: a one-way 13 L douglas bag with a mixture matching the end-tidal gasses as determined by the short pre-recording will be placed over the gas mask. In this instance, this is a closed circuit, and the bag will progressively fill with expired air, which the participant will breath in (e.g. continuously falling O2 and rising CO2). This will induce continuous global deoxygenation in the participant. Rebreathing will continue until the participant displays 70% SpO2 (roughly 6-9 minutes). A blood draw will then occur. Participants will then be returned to atmospheric breathing for 7 minutes, repeating the cycle a further 2 times (total 3 rebreathing phases), including blood draws. After a final atmospheric breathing phase, participants will breath from a two-way 13L douglas bag that is continuously supplied with pure O2; i.e. exhaled gasses return to the atmosphere while inhaled gasses (pure O2) come directly from the bag. This hyperoxic phase will last for 7 minutes, and be followed by a washout until the participant’s SpO2 falls to baseline levels. A graph of the approximate timings is seen below.

Participants will be informed of the protocol and risks over email and in-person on the day of the study by the researchers. They will be free to ask questions and withdraw without any repercussions, both before and within the trial.

Fidelity to the intervention will be monitored using check-sheets which will be completed by the operating researcher.
Intervention code [1] 317142 0
Diagnosis / Prognosis
Intervention code [2] 317143 0
Early detection / Screening
Comparator / control treatment
The active rebreathing periods, re-atmospherisation, and hyper-oxygenation periods will be compared to the non-active baseline recording period that occurs immediately prior to intervention.
Control group
Active

Outcomes
Primary outcome [1] 323252 0
Transverse relaxation times (T2) as measured by the MR-device.
Timepoint [1] 323252 0
These measures are continuous in nature, and will be acquired during the entire ~90 minute recording period, but their average values at steady altitude states and slopes during transitory phases will be extrapolated.
Primary outcome [2] 323253 0
Peripheral oxygenation (haemoglobin saturation) via SpO2 clip.
Timepoint [2] 323253 0
These measures are continuous in nature, and will be acquired during the entire ~90 minute recording period, but their average values at steady altitude states and slopes during transitory phases will be extrapolated.
Primary outcome [3] 323254 0
Using blood drawn from the median cubital vein catheter, we will perform blood gas analysis with the iStat to determining partial pressure of oxygen (PvO2) and haemoglobin saturation with oxygen (SvO2). These measures are derived in the same test and are therefore composite.
Timepoint [3] 323254 0
These are discontinuous measures. They will be obtained at the end of each phase (Atmospheric baseline, 7 minutes; Rebreathing (hypoxic hypercapnia), ~14, 28, 42 minutes; re-atmospherisation, ~21, 35, and 49, ~80-90 minutes; and hyperoxygenation, ~56 minutes).
Secondary outcome [1] 381317 0
Heart rate via ECG, from the Equivital vest.
Timepoint [1] 381317 0
This is a continuous measure and will be recorded for the entirety of each study.
Secondary outcome [2] 381318 0
Respiratory rate from the Equivital vest.
Timepoint [2] 381318 0
This is a continuous measure and will be recorded for the entirety of each study.
Secondary outcome [3] 381319 0
Surface temperature from the Equivital vest.
Timepoint [3] 381319 0
This is a continuous measure and will be recorded for the entirety of each study.
Secondary outcome [4] 381832 0
A measure of peripheral oxygenation, end-tidal oxygen pressure (PetO2), will be derived from the respiratory gas line attached to the rebreathing mask.
Timepoint [4] 381832 0
This is a continuous measure and will be acquired for the entirety of the recording period, approximately 90 minutes.

Eligibility
Key inclusion criteria
18-50 years old
Generally healthy
Non-smoker
People with a BMI 18.5-30 kg m^-2
Minimum age
18 Years
Maximum age
50 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
History of migraines
History of respiratory or cardiovascular disease or specific renal impairment.
Currently taking diuretics, antacids, proton pump inhibitors, or histamine blockers.
Smoking
Under 18 or over 50 years of age
History of stroke or other neurological conditions
Pregnancy
A contrast enhanced medical scan in the past week
There will also be a set of within-trial cessation criteria: a resting heart rate above 140 bpm, a peripheral O2 saturation below 70%, subject intolerance or request, sudden headache or nausea, or mental abnormalities as assessed by a clinician (i.e.: confusion, incoordination of motor skills).

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)
All participants are exposed to active intervention within the scope of a single study, which utilises baseline, within-study controls. Due to visual and physiological indications of current rebreathing state, no efforts are made to conceal the phase of the study. However, post-hoc analysis is performed in a blinded manner. participants and acute rebreathing conditions will be de-identified.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
All participants are exposed to only a single interventional protocol. No sequence is required.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Baseline (control) is within-participant/study.
Phase
Phase 0
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
These are pilot studies of a novel prototype device; we have no indication of the magnitude of the changes we will see, and as such, we cannot determine the necessary participant number to reach appropriate statistical power. As a pilot study, we are predominantly aiming to determine the presence (or lack thereof) phenomenological changes in our device’s measurements in response to our manipulations.

Despite this, crude statistics will be performed, e.g. Linear regression analysis of continuous oxygenation measure slopes (SpO2, PvO2, SvO2, T2 via the Luz-Meiboom equation); i.e. correlation of the measurements.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 22440 0
New Zealand
State/province [1] 22440 0
Wellington

Funding & Sponsors
Funding source category [1] 305269 0
University
Name [1] 305269 0
University of Otago Wellington Dean’s Grant
Address [1] 305269 0
University of Otago Wellington
23A Mein Street
Newtown
Wellington
6021
Country [1] 305269 0
New Zealand
Primary sponsor type
Individual
Name
A/Prof. Shieak Tzeng
Address
23A Mein Street,
Newtown,
Wellington
6021
Country
New Zealand
Secondary sponsor category [1] 305633 0
None
Name [1] 305633 0
Address [1] 305633 0
Country [1] 305633 0
Other collaborator category [1] 281241 0
Commercial sector/Industry
Name [1] 281241 0
Wellumio Inc.
Address [1] 281241 0
Suite 241, 32 Salamanca Road
Kelburn
Wellington
6012
Country [1] 281241 0
New Zealand

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 305614 0
Human and Dissability Ethics Committee
Ethics committee address [1] 305614 0
Postal Address:
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140

Street address:
133 Molesworth Street
Thorndon
Wellington 6011
Ethics committee country [1] 305614 0
New Zealand
Date submitted for ethics approval [1] 305614 0
19/06/2020
Approval date [1] 305614 0
Ethics approval number [1] 305614 0

Summary
Brief summary
The purpose of this study is to test the validity and reproducibility of a novel magnetic resonance (MR) based device for the detection of brain oxygenation under dynamic conditions. This will be achieved by subjecting participants to a rebreathing protocol to induce continuous changes in oxygen saturation, and comparing the device readings to accepted measurements, like peripheral blood gas analysis, respiratory gas analysis, and infrared oxygen saturation (SpO2).

The protocol is derived from historical and recent research using acute intermittent hypercapnic hypoxia (i.e. cyclic periods of low oxygen and high carbon dioxide) which resulted in oxygen saturations as low as 50% with no health effects outside of the brief studies.

We hypothesise that the changes in brain oxygenation measured by our device (T2 relaxation time via the Luz-Meiboom equation) that will be induced by our experimental activities will be statistically comparable to the same changes tracked with other modalities. This ability to track brain oxygenation levels is vital to a number of neurological conditions, including stroke.

Validating this sensitivity, the safety of the device, and the reproducibility of the results constitutes the first stage of getting the device approved for use and commercially available. The device is portable and relatively inexpensive compared to its ortholog, MRI. Plus, it offers continuous measurement compared to the ‘snapshot’ nature of its counterpart. Its availability is posed to reduce the burden on MRI unavailability (longer diagnosis times, lower treatment rates, more death and disability) from the populations most affected: rural and low-middle income countries.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 100962 0
A/Prof Max Berry
Address 100962 0
University of Otago Wellington
23A Mein Street
Newtown
Wellington
6021
Country 100962 0
New Zealand
Phone 100962 0
+64 21 244 9929
Fax 100962 0
Email 100962 0
max.berry@otago.ac.nz
Contact person for public queries
Name 100963 0
Ms Freya Harrison
Address 100963 0
LB309
Gate 7, Kelburn Parade
Victoria University of Wellington
Kelburn
Wellington
6021
Country 100963 0
New Zealand
Phone 100963 0
+64 20 4147 8190
Fax 100963 0
Email 100963 0
freya.harrison@vuw.ac.nz
Contact person for scientific queries
Name 100964 0
Mr Dion Thomas
Address 100964 0
LB309
Gate 7, Laby Building
Victoria University Wellington
Kelburn Parade
Kelburn
6012
Country 100964 0
New Zealand
Phone 100964 0
+64 21 063 0139
Fax 100964 0
Email 100964 0
dion.thomas@vuw.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Data derived from the novel device is subject to intellectual property protection, as would be any signal processing methodology which would be created to analyse this novel-format data output from the prototype device.
What supporting documents are/will be available?
No other documents available
Summary results
No Results