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Trial registered on ANZCTR


Registration number
ACTRN12619000721101
Ethics application status
Approved
Date submitted
29/03/2019
Date registered
14/05/2019
Date last updated
14/05/2019
Date data sharing statement initially provided
14/05/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Exploring the effect of Continuous Positive Airway Pressure (CPAP) treatment withdrawal on markers of brain health and memory and thinking skills
Scientific title
Examining biological markers of oxidative stress over time in patients with obstructive sleep apnoea following CPAP treatment withdrawal
Secondary ID [1] 297882 0
N/A
Universal Trial Number (UTN)
Trial acronym
CPAP withdrawal
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obstructive Sleep Apnoea 310283 0
Condition category
Condition code
Respiratory 309021 309021 0 0
Sleep apnoea

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Following initial screening, and after obtaining informed consent, potential participants will be invited to complete a 4-day trial of CPAP withdrawal to confirm eligibility. Participants will then return to treatment as usual for a minimum of 2-weeks before taking further part in the trial.
Participants will then attend the Healthy Brain Ageing (HBA) Research Clinic at the Brain and Mind Centre (BMC) to complete baseline characterization of their cognition, quality of life, physical health status, mood and other descriptives. A baseline MRI scan and measure of arterial stiffness will also be conducted at this time. After completing the baseline assessment, participants will stay overnight at the Woolcock Institute of Medical Research (WIMR) completing memory consolidation tasks in the 1 hour prior to habitual sleep onset, and 1 hour after waking.
Pre- and post-sleep MRI scans will be collected at follow-up assessments, along with measures of overnight memory consolidation and arterial stiffness. Participants will remain on treatment as usual for the first 7-days, followed by CPAP withdrawal for 14-days. All assessments and oversight of the intervention will be conducted by researchers at the WIMR. A summary of the time commitment required for participation and the study procedure is provided below:

• Days -18 to -14: Eligibility screening followed by 4-day CPAP withdrawal eligibility
confirmation
• Days -14 to 0: 2-week washout period – Treatment as usual
• Day 0: Baseline assessment – Treatment as usual
• Day 7: Follow-up 1 – CPAP therapy withdrawal
• Day 14: Follow-up 2 – continued CPAP therapy withdrawal
• Day 21: Follow-up 3 – End of trial; Participant returned to treatment as usual

CPAP withdrawal will involve participants complete cessation of the use of their CPAP treatment. Compliance during the treatment as usual phase and the CPAP withdrawal phase will be monitored via data computed by and downloaded directly from the participant's CPAP device. Participants will also complete a sleep diary during the CPAP withdrawal phase. Treatment as usual is as per the participant's individual prescription from their sleep technician at the time of obstructive sleep apnoea diagnosis.
Intervention code [1] 312820 0
Other interventions
Comparator / control treatment
Biological, cognitive and mood outcomes will be assessed during the treatment as usual phase, and directly compared to the participant's outcomes during the CPAP withdrawal phase.
Control group
Active

Outcomes
Primary outcome [1] 320035 0
Feasibility, as indicated by recruitment rate, participant attrition rates and study completion.
Timepoint [1] 320035 0
Baseline, follow-up assessment 1 (day 7), follow-up assessment 2 (day 14), follow-up assessment 3 (day 21).
Primary outcome [2] 320036 0
Acceptability as defined by participant compliance with study protocol and completion of assessment measure outcomes at all study timepoints.
Timepoint [2] 320036 0
Baseline, follow-up assessment 1 (day 7), follow-up assessment 2 (day 14), follow-up assessment 3 (day 21).
Secondary outcome [1] 353558 0
Changes in markers of oxidative stress, as determined by measures of neuronal glutathione assessed via magnetic resonance spectroscopy scans.
Timepoint [1] 353558 0
Baseline, follow-up assessment 1 (day 7), follow-up assessment 2 (day 14), follow-up assessment 3 (day 21).
Secondary outcome [2] 368838 0
Changes in markers of systemic inflammation and oxidative stress (as a composite, exploratory outcome), as determined by blood markers of inflammation (such as C-reactive protein).
Timepoint [2] 368838 0
Baseline, follow-up assessment 1 (day 7), follow-up assessment 2 (day 14), follow-up assessment 3 (day 21).
Secondary outcome [3] 369050 0
Changes in objective sleep quality, including sleep efficiency, habitual sleep onset/offset time and wake after sleep onset (as a composite outcome), as recorded by actigraphy.
Timepoint [3] 369050 0
CPAP withdrawal screening, baseline, follow-up assessment 1 (day 7), follow-up assessment 2 (day 14), follow-up assessment 3 (day 21).
Secondary outcome [4] 369051 0
Changes in objective sleep quality, including sleep efficiency, awakenings and SpO2 (as a composite outcome), as recorded by NightOwl.
Timepoint [4] 369051 0
CPAP withdrawal screening, baseline, follow-up assessment 1 (day 7), follow-up assessment 2 (day 14), follow-up assessment 3 (day 21).
Secondary outcome [5] 369053 0
Procedural learning and memory, as determined by finger tapping tasks.
Timepoint [5] 369053 0
Baseline, follow-up assessment 1 (day 7), follow-up assessment 2 (day 14), follow-up assessment 3 (day 21).
Secondary outcome [6] 370320 0
Change in affect as determined by the Hamilton Depression Inventory (HAM-D).
Timepoint [6] 370320 0
Baseline, follow-up assessment 1 (day 7), follow-up assessment 2 (day 14), follow-up assessment 3 (day 21).
Secondary outcome [7] 370321 0
Change in affect as determined by the Depression Anxiety Stress Scale (DASS-21).
Timepoint [7] 370321 0
CPAP withdrawal screening, 2-week washout period.
Secondary outcome [8] 370322 0
Cardiovascular changes, as determined by measures of arterial stiffness and central aortic pressure (indicated by pulse wave analysis and pulse wave velocity as a composite outcome).
Timepoint [8] 370322 0
Baseline, follow-up assessment 1 (day 7), follow-up assessment 2 (day 14), follow-up assessment 3 (day 21).

Eligibility
Key inclusion criteria
• Be greater than 50 years old at time of assessment.
• Be fluent in English.
• Have been previously diagnosed with OSA.
• Be currently undertaking CPAP therapy for more than 3 months with good compliance.
• Be willing to attend appointments at both the Woolcock Institute of Medical Research
and Brain and Mind Centre.
Minimum age
50 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Have a suspected dementia or amnestic MCI on Telephone interview for the Cognitive
Status score of <31
• Have a history of stroke or other neurological disorder
• Have a current neurological or psychiatric condition (e.g. schizophrenia)
• History of cardiac atrial fibrillation
• Have an intellectual disability
• Have a current affective disorder (e.g. depression, anxiety)
• Are a shift-worker
• Have current or future plans for trans-meridian travel during the trial period
• Are currently taking any medications known to affect sleep
• Have any contraindications for MRI scanning (e.g. pacemaker)
• Do no demonstrate OSA symptom relapse (specifically apnoeas/hypoapnoeas)

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis
The total sample size for this study is 15. Based on our work, we have allowed for ~10% attrition and expect a medium effect size increase in neurobiological markers of oxidative stress over time. However this work is novel and within this pilot study we seek to determine the actual effect size. It is estimated that we will have greater than 80% power with the 15 participants. The outcomes of this study will be used to power a larger more rigorous randomized controlled trial.

Group differences at baseline will be assessed using independent samples t-tests for continuous data and chi-squared tests for categorical data (such as gender). A repeated measures analysis of variance will be used to examine group differences in primary and secondary outcomes.

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 in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 301092 0
Government body
Name [1] 301092 0
NHMRC CRE Neurosleep Grant
Address [1] 301092 0
Level 1, 16 Marcus Clarke Street
Canberra City, ACT, 2601
Country [1] 301092 0
Australia
Funding source category [2] 302363 0
Government body
Name [2] 302363 0
NHMRC National Institute for Dementia Research
Address [2] 302363 0
Level 1, 16 Marcus Clarke Street
Canberra City, ACT, 2601
Country [2] 302363 0
Australia
Primary sponsor type
University
Name
The Woolcock Institute of Medical Research, University of Sydney
Address
Woolcock Institute of Medical Research,
The University of Sydney
431 Glebe Point Rd,
Glebe NSW 2037?NSW 2006 Australia
Country
Australia
Secondary sponsor category [1] 300921 0
None
Name [1] 300921 0
Address [1] 300921 0
Country [1] 300921 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301841 0
Royal Prince Alfred Hospital Human Research Ethics Committee
Ethics committee address [1] 301841 0
Research Ethics and Governance Office (REGO)
Royal Prince Alfred Hospital
Missenden Road
CAMPERDOWN NSW 2050
Ethics committee country [1] 301841 0
Australia
Date submitted for ethics approval [1] 301841 0
16/07/2018
Approval date [1] 301841 0
04/09/2018
Ethics approval number [1] 301841 0
X18-0283 & HREC/18./RPA/396

Summary
Brief summary
This feasibility study aims to explore whether the withdrawal of Continuous Positive Airway Pressure (CPAP) therapy affects markers of brain health (such as oxidative stress) and/or memory over a 14-day period. The study will also identify the time point at which CPAP withdrawal has the greatest effect on markers of brain health to facilitate planning for a larger randomized controlled trial. We hypothesize that CPAP withdrawal will result in an increase in oxidative stress in treatment compliant OSA patients. Furthermore, we also hypothesize that increases in oxidative stress will be negatively associated with sleep dependent memory consolidation and greater affective symptom severity over time.

Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 88290 0
Dr Shantel Duffy
Address 88290 0
Level 2, Building D17
Johns Hopkins Drive
Camperdown
Charles Perkins Centre
NSW 2050
Rm 305
Building M02F
94 Mallet St, Camperdown
Brain and Mind Centre
NSW 2050
Level 4 /431 Glebe Point Road
Glebe
Woolcock Institute of Medical Research
NSW 2037
Country 88290 0
Australia
Phone 88290 0
+61 2 8627 1807
Fax 88290 0
Email 88290 0
shantel.duffy@sydney.edu.au
Contact person for public queries
Name 88291 0
Mr Bradley Skinner
Address 88291 0
Building M02G
94 Mallet St, Camperdown
Brain and Mind Centre
NSW 2050
Country 88291 0
Australia
Phone 88291 0
+61 2 9351 0901
Fax 88291 0
Email 88291 0
bradley.skinner@sydney.edu.au
Contact person for scientific queries
Name 88292 0
Dr Shantel Duffy
Address 88292 0
Level 2, Building D17
Johns Hopkins Drive
Camperdown
Charles Perkins Centre
NSW 2050
Rm 305
Building M02F
94 Mallet St, Camperdown
Brain and Mind Centre
NSW 2050
Level 4 /431 Glebe Point Road
Glebe
Woolcock Institute of Medical Research
NSW 2037
Country 88292 0
Australia
Phone 88292 0
+61 2 8627 1807
Fax 88292 0
Email 88292 0
shantel.duffy@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?
All of the individual participant data collected during the trial, after de-identification.
When will data be available (start and end dates)?
Immediately following publication of main results, no end date determined.
Available to whom?
Only researchers who provide a methodologically sound proposal.
Available for what types of analyses?
Only to achieve the aims in the approved proposal.
How or where can data be obtained?
Access is subject to approvals by the Principal Investigator.
What supporting documents are/will be available?
Study protocol
Statistical analysis plan
Informed consent form
Ethical approval
Summary results
No Results