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Trial registered on ANZCTR


Registration number
ACTRN12614001202651
Ethics application status
Approved
Date submitted
30/10/2014
Date registered
17/11/2014
Date last updated
19/07/2019
Date data sharing statement initially provided
27/05/2019
Date results information initially provided
27/05/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Can early treatment prevent obstructive sleep apnoea-related brain damage?
Scientific title
Can continuous positive airway pressure treatment of patients with moderate obstructive sleep apnoea prevent sleep apnoea-related brain damage?
Secondary ID [1] 285413 0
Nil known
Universal Trial Number (UTN)
U1111 1162 - 0719
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Moderate obstructive sleep apnoea (between 15 and 29 hypopnoea or apnoea events per hour during sleep). 293161 0
Sleep apnoea-related brain damage. 293446 0
Condition category
Condition code
Neurological 293433 293433 0 0
Other neurological disorders
Respiratory 293434 293434 0 0
Sleep apnoea

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Six months of continuous positive airway pressure (CPAP) for at least 4 hours per night. CPAP works by blowing air into the pharynx during sleep thereby raising the air pressure sufficiently to hold the airway open.
This treatment will be administered via a mask around the mouth and nose. The dose setting for each patient is set by the CPAP device that uses an algorithm to set the optimal dose. This dosage will be monitored by the Sleep Unit.
Compliance will be monitored remotely by downloading the data cards used in the CPAP device.
Intervention code [1] 290331 0
Treatment: Devices
Comparator / control treatment
A comparison will be made between baseline and measures after six months of CPAP treatment on a battery of cognitive tests, number of microsleep events during a 50 min continuous tracking task, and cerebral perfusion in people with moderate OSA.
All measures (at baseline and 6 months) will also be compared against data from (1) a group of participants without OSA and (2) a group of participants with moderate OSA who had not received CPAP treatment,
Control group
Active

Outcomes
Primary outcome [1] 293257 0
Number of behavioural microsleeps during a 50 min continuous tracking task following six months of CPAP treatment compared with number of behavioural microsleeps at baseline and those with untreated moderate OSA or without OSA. Microsleeps are identified by correlating periods of non-activity identified by reviewing tracking performance data with obvious overt signs of drowsiness identified from synchronized eye-vidoe with tracking data. The target used in the tracking task moves randomly without any flats spots. Therefore any flat spots in performance represent unintentional non-response.
Timepoint [1] 293257 0
Following six months of CPAP treatment.
Primary outcome [2] 293258 0
Cerebral perfusion measured using arterial spin labelling (ASL) in a magnetic resonance imaging (MRI) scanner following six months of CPAP treatment compared with cerebral perfusion at baseline and those with untreated moderate OSA or without OSA.
Timepoint [2] 293258 0
Following six months of CPAP treatment.
Primary outcome [3] 293260 0
Performance on a battery of cognitive tests (Stroop Colour-Word Interference Task, Trailmaking Test B, Digits Forward and Backwards, and Letter and Category Fluency Test) following six months of CPAP treatment compared with performance at baseline and those with untreated moderate OSA or without OSA.
Timepoint [3] 293260 0
Following six months of CPAP treatment.
Secondary outcome [1] 310689 0
Cerebral perfusion at baseline in people with moderate OSA compared with cerebral perfusion in people without OSA. Cerebral perfusion will be measured using arterial spin labelling in a magnetic resonance imaging scanner.
Timepoint [1] 310689 0
Baseline.
Secondary outcome [2] 310710 0
Compliance rate with CPAP treatment as measured by the mean number of hours of CPAP usage per night. The data for this measure will be obtained by downloading the data card in the CPAP device.
Timepoint [2] 310710 0
At one month, three months and six months following the beginning of CPAP treatment.

Eligibility
Key inclusion criteria
All participants:
Be at least 18 yrs but no older than 80 yrs.
Normal time to bed between the hours of 0900 pm and 1200 am.
Normal time in bed of 7 to 9 hours.
Have a basic ability in English (verbal and written).

Participants with moderate OSA:
Be diagnosed with moderate OSA (15 - 29 OSA-related events per hour during Level 2 Sleep Study.

Participants without OSA:
Have <10 OSA-related events per hour during Level 2 Sleep Study.
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Currently receiving or previously received OSA treatment.
A history of physiological, psychiatric, or neurological disorders that could affect or is affecting sleep behaviour, fatigue, cerebral perfusion or brain structure (e.g. chronic obstructive pulmonary disease, congestive heart disease, diabetes, heart failure, hypertension > 150/90, migraine, myocardial infarction, stroke, previous brain surgery, stroke, traumatic brain injury, etc., but not mild depression).
Currently taking any medication that could impact on cerebral perfusion (e.g., ACE inhibitors, nitrates …).
Not willing or unable to give consent.
Not willing or unable to remove metal that could either be harmful to the participant during a MRI or could likely create MRI artefacts that negatively affect the quality of the scan.
Based on current Sleep Unit criteria, not have any reason for urgent treatment.

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)
Not applicable.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
This is a longitudinal study of n=30 people with moderate OSA and n=15 controls without OSA. Unpaired t-tests will be used to compare microsleep propensity and cerebral perfusion at baseline between controls and moderate OSA (80% power for detecting an effect size of = 0.69). Correlation analysis will be used for OSA severity and microsleep propensity, cerebral perfusion, and cognitive test scores at baseline and at 6 months (80% power for detecting a correlation = 0.42). A repeated-measures ANOVA will be used for changes in microsleep propensity and cerebral perfusion for within- and between-group interactions from baseline to 6 months between mod OSAs and controls (80% power for detecting an effect size = 0.20). Unpaired t-tests will be used to compare microsleep propensity and cerebral perfusion at 6 months, between controls and mod OSAs (80% power for detecting an effect size of = 0.73). Paired t-tests will be used to compare microsleep propensity, cerebral perfusion, and cognitive test scores pre- and post-CPAP treatment in mod OSAs (80% power for detecting an effect size of = 0.58). In general, moderate to large effect sizes (0.5–0.8) need to be observed to provide clinically relevant results.

Recruitment
Recruitment status
Completed
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] 6381 0
New Zealand
State/province [1] 6381 0
Canterbury

Funding & Sponsors
Funding source category [1] 290021 0
Charities/Societies/Foundations
Name [1] 290021 0
Canterbury Medical Research Foundation
Address [1] 290021 0
Level 1
230 Antigua Street
Christchurch 8011
Country [1] 290021 0
New Zealand
Funding source category [2] 299779 0
Charities/Societies/Foundations
Name [2] 299779 0
Lottery Health Research Grant
Address [2] 299779 0
Lottery Grants Board
c/- The Department of Internal Affairs.
PO Box 805
Wellington 6140
Country [2] 299779 0
New Zealand
Primary sponsor type
Individual
Name
Dr. Carrie Innes
Address
Dr Carrie Innes
C/- New Zealand Brain Research Institute
66 Stewart Street,
Christchurch 8011
Country
New Zealand
Secondary sponsor category [1] 288712 0
None
Name [1] 288712 0
Address [1] 288712 0
Country [1] 288712 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291729 0
Health and Disability Ethics Committee
Ethics committee address [1] 291729 0
Ministry of Health
No 1 The Terrace
PO Box 5013
Wellington 6011
Ethics committee country [1] 291729 0
New Zealand
Date submitted for ethics approval [1] 291729 0
22/10/2014
Approval date [1] 291729 0
24/11/2014
Ethics approval number [1] 291729 0

Summary
Brief summary
The aim of this study is to investigate brain structure, cerebral blood perfusion, cognition, and microsleep propensity at baseline and following 6 months of CPAP treatment in people with moderate obstructive sleep apnoea (OSA) compared to (1) people without OSA and (2) people with untreated moderate OSA.

We hypothesize that:
(1) CPAP treatment will improve cerebral perfusion while awake at the 6-month follow-up.
(2) There is a relationship between OSA-related decreased cerebral perfusion and cognitive impairment.
(3) CPAP treatment will reduce microsleep propensity.
Trial website
Trial related presentations / publications
Public notes
Participants in the moderate OSA group will be referrals from the Christchurch Hospital Sleep Unit who have been assessed as having moderate OSA and do not require urgent treatment. Sleep Unit staff will make the initial approach. Those who indicate a willingness to participate will be contacted by the Study Coordinating Investigator who will provide detailed information concerning the study and confirm inclusion criteria are met and no exclusion criteria apply. Provided informed consent is given, an offer to participate will be made. The first 15 participants accepted into the study with moderate OSA will be assigned to the treatment group and the second 15 participants with moderate OSA will be assigned to the non-treatment group.
A separate group of 15 participant without OSA were recruited through personal contacts and advertisements.

Contacts
Principal investigator
Name 51758 0
Dr Carrie Innes
Address 51758 0
c/- New Zealand Brain Research Institute,
66 Stewart St.,
Christchurch 8011
Country 51758 0
New Zealand
Phone 51758 0
+64 3 378 6096
Fax 51758 0
Email 51758 0
Carrie.Innes@nzbri.org
Contact person for public queries
Name 51759 0
Prof Richard Jones
Address 51759 0
c/- New Zealand Brain Research Institute,
66 Stewart St.,
Christchurch 8011
Country 51759 0
New Zealand
Phone 51759 0
+64 3 378 6077
Fax 51759 0
Email 51759 0
richard.jones@nzbri.org
Contact person for scientific queries
Name 51760 0
Dr Carrie Innes
Address 51760 0
c/- New Zealand Brain Research Institute,
66 Stewart St.,
Christchurch 8011
Country 51760 0
New Zealand
Phone 51760 0
+64 3 378 6096
Fax 51760 0
Email 51760 0
Carrie.Innes@nzbri.org

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
IPD sharing not planned
What supporting documents are/will be available?
Study protocol
Informed consent form
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary