Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619001067167
Ethics application status
Approved
Date submitted
1/05/2019
Date registered
31/07/2019
Date last updated
1/12/2020
Date data sharing statement initially provided
31/07/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
A new clinical tool to assess fitness-to-drive in obstructive sleep apnea
Scientific title
A new clinical tool to assess fitness-to-drive in obstructive sleep apnea
Secondary ID [1] 296320 0
NHMRC-GNT1143089
Universal Trial Number (UTN)
Trial acronym
DASA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obstructive Sleep Apnea 310030 0
Condition category
Condition code
Respiratory 308782 308782 0 0
Sleep apnoea

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Following a screening visit and obtaining informed consent, participants undergo one week of activity monitoring and sleep diary assessments, followed by a two-day experimental laboratory protocol.

Following a screening visit and obtaining informed consent, participants undergo one week of activity monitoring and sleep diary assessments, followed by a two-day experimental laboratory protocol.

The experimental laboratory protocol starts in the evening of day 1 with an overnight baseline polysomnography assessment. On the second day, participants will be woken up between 6:00 and 6:30 am and will remain awake for an extended period of 22 hours. Throughout the protocol, adherence to remain awake will be monitored with CCTV and direct surveillance. All participants will undergo a 90-minute assessment of driving simulator tests (primary performance outcome) at baseline (~2 hours awake at 8:00 am) and with extended wakefulness (~19 hours wake at 1:00 am), which is administered and monitored by the researcher. For the duration of the test, the participant will be seated behind a desk with foot pedals and a steering wheel behind a 22-inch monitor. Selected candidate biomarker measures are obtained in 5 blocks of neurobehavioral test batteries, 4 maintenance of wakefulness tests (MWT), and two blood samples obtained prior and after the two driving tests respectively. The neurobehavioral tests commence at 9:00 and are repeated every 2 hours. The MWT commences at 10:00 and is repeated every 2 hours. Participants may opt-out for blood sampling without affecting their participation. The repetition of biomarker assessments allows to evaluate the stability and test-retest reliability of baseline biomarkers as well as refining the optimal testing period during the circadian day. Healthy age- and gender-matched healthy control participants will undergo the identical protocol to establish normative thresholds for driving and neurobehavioral performance. At the end of the extended wakefulness period, participants are given the opportunity to sleep as normal in the lab or being discharged with the possibility to be driven home by taxi.

The focus of this study is to use an extended-wakefulness protocol to test driving performance, routine clinical sleep study metrics and the identified candidate biomarkers in a new cohort of OSA patients, and divide them into vulnerable versus resistant groups, based on normal control data cut-offs. We will complete a phase-1 diagnostic test evaluation study to validate the predictive value of candidate biomarkers identified in our discovery study and contrast this with the MWT in differentiating between OSA patients who are vulnerable versus those who are resistant to alertness failure.

The focus of this study is to use an extended-wakefulness protocol to test driving performance, routine clinical sleep study metrics and the identified candidate biomarkers in a new cohort of OSA patients, and divide them into vulnerable versus resistant groups, based on normal control data cut-offs. We will complete a phase-1 diagnostic test evaluation study to validate the predictive value of candidate biomarkers identified in our discovery study and contrast this with the MWT in differentiating between OSA patients who are vulnerable versus those who are resistant to alertness failure.
Intervention code [1] 312650 0
Early detection / Screening
Comparator / control treatment
We will compare the accuracy of previously identified biomarkers to predict driving performance after an extended period of wakefulness with the predictive value of the current gold-standard Maintenance of Wakefulness Test.
Control group
Active

Outcomes
Primary outcome [1] 307763 0
The number of simulated crashes as assessed by the driving simulation test.
Timepoint [1] 307763 0
Assessed during the driving test at 1 am after 19 hours of wakefulness.
Secondary outcome [1] 352809 0
Driving simulator lateral steering deviation. All other neurobehavioral tests, MWTs, and blood samples are used to compute predictors for the primary and secondary outcomes.
Timepoint [1] 352809 0
Assessed during the driving test at 1 am after 19 hours of wakefulness.

Eligibility
Key inclusion criteria
• Both males and females
• An age between 25 and 65 years
• Holder of a current driver's licence
• Ability to speak and write in English language
• Ability to perform neurobehavioral tests
• For OSA patients: PSG confirmed AHI over 10 per hour, Oxygen Desaturation Index greater than or equal to 3% and over 8 per hour.
Minimum age
25 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
• Occupation as a shift-worker (i.e. between 1 and 6 am)
• Inexperienced driver: <2 hours/week and < 2 years
• If female, pregnancy or breastfeeding
• Transmeridian travel with >2 hours time-difference in the past 2 months
• Usage of sleep medication in the past 2 months
• Past or current treatment of sleep-apnea (CPAP or mandibular advancement device)
• Use of recreational drugs, cigarettes, tobacco, or other smoking products
• Regular consumption of alcohol: an average of >4 standard drinks/day
• Diagnosis of severe (neuro)physiological or psychiatric disorders

Study design
Purpose of the study
Prevention
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
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis
1) Defining the upper limits in lateral steering deviation (see primary and secondary outcomes) in healthy controls that can subsequently be used as cut-offs to distinguish vulnerable and resistant patient-groups to performance failures.
2) Development of a predictive general-linear model aiming to predict the vulnerable and resistant patient-groups based on the set of previously identified biomarkers.
3) The performance of this model will be evaluated by its receiver operating characteristic, sensitivity and specificity, and positive and negative predictive value.
4) Another predictive general-linear model will be developed using only data from the gold-standard maintenance of wakefulness tests, and the performance of these two models will be compared. The novel "biomarker" model should perform at least as well, if not better, as compared to the gold-standard.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
9/07/2019
Date of last participant enrolment
Anticipated
30/11/2020
Actual
Date of last data collection
Anticipated
7/12/2020
Actual
Sample size
Target
100
Accrual to date
19
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA

Funding & Sponsors
Funding source category [1] 300916 0
Government body
Name [1] 300916 0
National Health and Medical Research Council
Country [1] 300916 0
Australia
Primary sponsor type
University
Name
Flinders University
Address
5 Laffer Drive, Bedford Park SA 5042
Country
Australia
Secondary sponsor category [1] 300481 0
Other
Name [1] 300481 0
Woolcock Institute of Medical Research
Address [1] 300481 0
431 Glebe Point Road, Glebe, NSW 2037
Country [1] 300481 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301684 0
Southern Adelaide Clinical Human Research Ethics Committee
Ethics committee address [1] 301684 0
Flinders Medical Centre, Ward 6C, Room 6A219, Flinders Drive, Bedford Park, SA 5042
Ethics committee country [1] 301684 0
Australia
Date submitted for ethics approval [1] 301684 0
06/06/2018
Approval date [1] 301684 0
10/12/2018
Ethics approval number [1] 301684 0
148.18 HREC/18/SAC/171

Summary
Brief summary
Obstructive sleep apnea (OSA) is a common sleep disorder linked with impaired driving performance. The problem is that the current standard tests to evaluate driving ability is very labour intensive and expensive, limiting its utility to only a small portion of OSA patients. The aim is to validate biomarkers of alertness failure and driving impairment in patients with OSA towards developing a clinically deployable, simplified and cost effect fitness to drive assessment. We expect that, on the basis of biomarkers that can be easily obtained in clinical sleep services, we can identify OSA patients at high risk of driving impairment and accidents, and distinguish them from patients who are at negligible risk.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 87782 0
Dr Andrew Vakulin
Address 87782 0
Adelaide Institute for Sleep Health, Level 2, Mark Oliphant Building, 5 Laffer Drive, Bedford Park SA 5042
Country 87782 0
Australia
Phone 87782 0
+61 8 72218308
Fax 87782 0
Email 87782 0
andrew.vakulin@flinders.edu.au
Contact person for public queries
Name 87783 0
Dr Andrew Vakulin
Address 87783 0
Adelaide Institute for Sleep Health, Level 2, Mark Oliphant Building, 5 Laffer Drive, Bedford Park SA 5042
Country 87783 0
Australia
Phone 87783 0
+61 8 72218308
Fax 87783 0
Email 87783 0
andrew.vakulin@flinders.edu.au
Contact person for scientific queries
Name 87784 0
Dr Andrew Vakulin
Address 87784 0
Adelaide Institute for Sleep Health, Level 2, Mark Oliphant Building, 5 Laffer Drive, Bedford Park SA 5042
Country 87784 0
Australia
Phone 87784 0
+61 8 72218308
Fax 87784 0
Email 87784 0
andrew.vakulin@flinders.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Knowledge acquired through this research may leads to discoveries that are of commercial value to Flinders University and Woolcock Institute of Medical Research. The evaluation of the intellectual property value will commence after the study has rendered its results.


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.

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