ANZCTR - Registration

Please note the ANZCTR will be unattended from Friday 20 December 2024 for the holidays. The Registry will re-open on Tuesday 7 January 2025. Submissions and updates will not be processed during that time.

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

Trial registered on ANZCTR

Registration number

ACTRN12613001171707

Ethics application status

Approved

Date submitted

8/10/2013

Date registered

24/10/2013

Date last updated

7/07/2022

Date data sharing statement initially provided

7/07/2022

Date results provided

7/07/2022

Type of registration

Retrospectively registered

Titles & IDs

Public title

Novel brain biomarkers of performance impairment in sleep apnea

Scientific title

Novel brain biomarkers of driving and vigilance performance in obstructive sleep apnea during extended wakefulness

Secondary ID [1]

None

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Obstructive Sleep Apnea

Condition category

Condition code

Respiratory

Sleep apnoea

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

85 patients with moderate-severe obstructive sleep apnea will be recruited to undergo an experimental laboratory protocol following a screening visit and after obtaining informed consent.
One week of actigraphy and sleep-wake diary and indoor-outdoor activity logs, will be performed prior to the test visit to measure sleep hours and activities at home, and participants will be advised to observe regular sleep hours with 8-hours in bed.

The experimental protocol visit consists:
- baseline sleep study followed by 28 hours of extended wakefulness challenge (EWC) with detailed assessment including:

Primary performance outcomes measure
-Three 90 minute computerised AusEd driving simulator tasks measured at Time 1 (9.30am, 3.5 hours awake), Time 2 (2.30am, 20.5 hours awake) and Time 3 (8.30am, 26.5 hours awake)

Secondary performance outcome measure
-10 minute psychomotor vigilance test (PVT) measures every 2 hours throughout the EWC starting from midday.

Primary Predictor Variables
-Baseline sleep study is performed from 10pm-6am (EEG data will be subjected to spectral power analysis as part of data processing/analysis)
-Auditory Event Related potentials (ERP) data will be collected at between 8.30-9.30am (baseline assessment only)
-Resting awake EEG during a 7 minute Karolinska Drowsiness Test measure every 2 hours throughout the EWC startinf at midday
-Magnetic Resonance Spectroscopy/Diffusion Tensor Imaging occurs within 1 week prior to laboratory EWC visit (assessed at baseline only)

Secondary Predictor Variables
-mRNA expression profiles from baseline to end of EWC (blood/mRNA samples collected at 6.15am upon awakening and 6.15am the following morning after 24hours of wakefulness
-Posture/Balance control assessments measured every 2 hours throughout the EWC starting at midday
-Peripheral Blood Pressure measures every 2 hours throughout the EWC starting at midday
Computerised performance tests measure every 2 hours through out the EWC starting at midday :
- Working memory (N-back 1,2,3)
- Visuomotor skills (Digit Symbol Substitution Task)
- 4 Choice Reaction Time Task
-Central Blood Pressure and Pulse Wave Analysis (PWA) measures every 2 hours throughout the EWC starting at midday
-Statistical Learning Task measured at baseline (8.30pm prior to baseline sleep study) and at 8.30pm 24 hours later.
-Actigraphy variables (actigraphy data collected 1 week prior to EWC)
-PSG sleep study variables (collected during the baseline sleep study just prior to EWC)
-Genetic polymorphisms (genetic analysis from blood samples collected at start and end of EWC will occur at the completion of the study)
-Inflammatory marker profiles (from blood sample analysis collected at start and end of EWC will occur at the completion of the study)
-Brief Smell Identification Test (B-SIT) is collected at baseline only at 7.30pm prior to baseline sleep study
-State anxiety questionnaire administered every 2 hours throughout the EWC starting at midday
-Karolinska Sleepiness Scale administered every 2 hours throughout the EWC starting at midday

Intervention code [1]

Behaviour

Comparator / control treatment

Uncontrolled

Control group

Uncontrolled

Outcomes

Primary outcome [1]

AusEd driving simulator lateral steering deviation

Timepoint [1]

Driving simulator assessments occur 3 times during the Extended Wakefulness Protocol:

-Time 1 (baseline - 3.5 hours awake)
-Time 2 (20.5 hours awake)
-Time 3 (26.5 hours awake)

Secondary outcome [1]

Psychomotor Vigilance Test (PVT) - a measure of simple reaction time and vigilance

Timepoint [1]

assessed every 2 hours during the EWC

Eligibility

Key inclusion criteria

Age 25-65 years
Weight <150kg
PSG confirmed moderate to severe obstructive sleep apnea with an Apnea Hypopnea Index (AHI) of =15 events/hr and an Oxygen Desaturation Index (ODI) of =3% with =10 events/hr
Ability to read and speak English
Ability to perform neurobehavioural tests

Minimum age

25 Years

Maximum age

65 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Other PSG confirmed sleep disorders
OSA patients with clinically significant uncontrolled co-morbidity such as: cardiac failure, hypertension, hypercapnia, COPD, Type 1 diabetes
History of head injury or psychiatric/neurological disorders: clinical depression, epilepsy, mania or psychosis, stroke
Currently using CNS active medications/drugs such as: anti-depressives, anti-psychotics, opiates, antihistamines

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

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Single group

Other design features

Cross-Sectional study

Phase

Not Applicable

Type of endpoint/s

Statistical methods / analysis

The key goal for this project will be obtaining predictors for vulnerability to sleep loss. Analysis is by multiple regression with change in AusEd steering deviation (vulnerability to sleep deprivation) as the primary outcome variable, and a range of candidate biomarkers as predictors, including measurements from MR, sleep/wake EEG and genetic polymorphisms. In a multiple regression model with up to 2 tested predictors adjusting for the another 1-2 additional predictors (covariates) with a significance level of 0.05, a sample size of 78 is required with power of 0.8 to detect a moderate multiple partial correlation coefficient of 0.35, between the tested predictors and the primary outcome variable. Variables not meeting assumptions for parametric statistics will be appropriately transformed. Factor analysis will be employed to assist with grouping similar variables, in order to reduce the number of potential predictors submitted for regression analysis. Secondary analyses will examine the change from rested to 8am the following morning (28 hours awake), and also examine the other outcomes of interest (PVT, n-back etc). We plan to recruit a total of 85 participants, to allow for 7 withdrawals.

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

6/09/2012

Actual

6/09/2012

Date of last participant enrolment

Anticipated

15/12/2014

Actual

19/11/2014

Date of last data collection

Anticipated

Actual

26/11/2014

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW

Recruitment hospital [1]

Royal Prince Alfred Hospital - Camperdown

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

National Health and Medical Research Council

Address [1]

GPO Box 1421
Canberra
ACT
2601

Country [1]

Australia

Primary sponsor type

Other

Name

Woolcock Institute of Medical Research

Address

431 Glebe Point Road
Glebe
NSW
2037

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Sydney Local Health District (RPAH Zone)

Ethics committee address [1]

c/- Research Development Office
Royal Prince Alfred Hospital
Missenden Road
CAMPERDOWN NSW 2050

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

19/03/2012

Ethics approval number [1]

HREC/12/RPAH/40

Summary

Brief summary

Obstructive sleep apnea (OSA) is a common cause of daytime sleepiness, impaired cognition, and has a 3 -13 times increased risk of motor vehicle crashes and double the rate of work accidents. This neurobehavioural dysfunction has a critical impact on health and society. 
One of the major challenges in dealing with this problem is the difficulty in clinically assessing neurobehavioural dysfunction such as impairment in driving ability. Many patients underestimate their impairment and there is wide inter-individual variability in how patients are affected by sleepiness and its consequences. For example, patients with sleep studies showing severe OSA may report few symptoms while others with apparent mild disease exhibit severe sleepiness. Unravelling this problem of inter-individual variability demands better assessment tools as conventional metrics such as sleep studies are uninformative. What is urgently needed are biomarkers, measured at a single or very limited time points that better reflect the individual risk of vigilance failure such as impaired driving.  
In this study, simulated driving and other performance tasks will be administered during a load of prolonged wakefulness extending throughout the night to unmask variation in neurobehavoural function  in OSA. Performance under these conditions will be related to practically deployable biomarkers (or combination of biomarkers) measured at baseline. We have compelling preliminary data on brain bioenergetics (magnetic resonance imaging), quantitative electroencephalogram (qEEG) and cortical activation (event related potentials) as candidate biomarkers for neurobehavioural impairment in OSA.  Such biomarkers would also be potentially valuable as tests to monitor treatment effectiveness or a phenotyping tools in molecular and genetic discovery in OSA.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Ronald Grunstein

Address

Ron Grunstein
Professor of Sleep Medicine and NHMRC Practitioner Fellow,
NHMRC Centre for Integrated Research and Understanding of Sleep (CIRUS), Woolcock Institute of Medical Research,
University of Sydney and Royal Prince Alfred Hospital

PO Box M77
Missenden Road
NSW
2050

Country

Australia

Phone

+61 2 91140007

Fax

rrg@med.usyd.edu.au

Contact person for public queries

Name

Andrew Vakulin

Address

Woolcock Institute of Medical Research
431 Glebe Point Road
Glebe
NSW
2037

Country

Australia

Phone

+61 2 9114 0443

Fax

andrew.vakulin@sydney.edu.au

Contact person for scientific queries

Name

Andrew Vakulin

Address

Woolcock Institute of Medical Research
431 Glebe Point Road
Glebe
NSW
2037

Country

Australia

Phone

+61 2 9114 0443

Fax

andrew.vakulin@sydney.edu.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

Yes

What data in particular will be shared?

Individual participant underlying published results only.

When will data be available (start and end dates)?

Data will be made available upon request, after publication, with no end date determined.

Available to whom?

Data will be made available upon request, after publication and will be determined upon negotiation with researchers who provided a methodologically sound proposal.

Available for what types of analyses?

Any purpose.

How or where can data be obtained?

Secure data transfer and signed data access agreement. Contact: andrew.vakulin@sydney.edu.au

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

Source	Title	Year of Publication	DOI
Embase	Sleep spindle activity correlates with implicit statistical learning consolidation in untreated obstructive sleep apnea patients.	2021	https://dx.doi.org/10.1016/j.sleep.2021.01.035
Embase	Brain mitochondrial dysfunction and driving simulator performance in untreated obstructive sleep apnea.	2022	https://dx.doi.org/10.1111/jsr.13482
Embase	Clinical predictors of working memory performance in obstructive sleep apnea patients before and during extended wakefulness.	2022	https://dx.doi.org/10.1093/sleep/zsab289

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Registering a new trial?

Documents added manually

Documents added automatically