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Trial registered on ANZCTR


Registration number
ACTRN12612000891820
Ethics application status
Approved
Date submitted
2/08/2012
Date registered
22/08/2012
Date last updated
22/12/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
Study to determine whether low-dose aspirin in healthy older adults prevents cognitive decline in those identified as having moderate to severe sleep apnoea: the SNORE-ASA substudy of the Aspirin in Reducing Events in the Elderly (ASPREE) study.
Scientific title
Study of Neurocognitive Outcomes, Radiological and retinal effects of Aspirin in Sleep Apnoea to determine the effects of daily low-dose aspirin 100mg versus placebo on cognitive outcomes in the setting of sleep apnoea, in healthy older adults aged 70 and over.
Secondary ID [1] 280959 0
Nil
Universal Trial Number (UTN)
U1111-1133-2126
Trial acronym
SNORE-ASA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cognitive decline 287066 0
Sleep Apnoea 287067 0
Condition category
Condition code
Neurological 287389 287389 0 0
Dementias
Respiratory 287390 287390 0 0
Sleep apnoea

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study is a sub study of the Aspirin in Reducing Events in the Elderly study (ASPREE, ClinicalTrials.gov identifier NCT01038583, website www.aspree.org). ASPREE is a double blinded, randomised controlled trial of low dose daily aspirin, 100mg oral tablets versus placebo, taken daily for five years in healthy participants aged 70 and over, followed over 5 years for the primary outcomes of dementia-free survival and disability-free survival. It is a primary prevention study.

The SNORE-ASA study will involve a subset of newly enrolling participants in the parent ASPREE study.

Prior to randomisation into the parent ASPREE study, SNORE-ASA participants take home a small, light and portable home sleep apnoea screening device named ApneaLink Plus. This device has a nasal cannula to measure airflow, a finger clip pulse oximeter, and can calculate the Apnoea Hypnoea Index (AHI) and Oxygen Desaturation Index (ODI), both of which are measures of the presence and severity of sleep apnoea. Participants are required to wear this for one night only, at study entry only.

While participants in the ASPREE study are randomised to oral aspirin 100mg or placebo taken once a day for five years, the SNORE-study outcome measures will be performed after 3 years. However, unblinding of whether the SNORE-ASA participants were randomised to either placebo or aspirin will not take place until after the 5 years of the parent ASPREE study.


A further subset of participants in the SNORE-ASA study will undergo a brain MRI and have retinal vascular imaging (also called retinal photography) at baseline and after 3 years to investigate the mechanism by which sleep apnoea may potentiate cognitive decline, and how aspirin may be protective against this.
Intervention code [1] 285398 0
Treatment: Drugs
Intervention code [2] 285407 0
Prevention
Intervention code [3] 285457 0
Early detection / Screening
Comparator / control treatment
placebo - identical in appearance to aspirin, with the same enteric coating.
Control group
Placebo

Outcomes
Primary outcome [1] 287658 0
Cognitive decline as measured by change in the modified mini mental state examination (3MS)
Timepoint [1] 287658 0
3 years
Secondary outcome [1] 298591 0
Change in brain MRI measures of white matter hyperintensity including volume
Timepoint [1] 298591 0
3 years
Secondary outcome [2] 298592 0
Change in Retinal Vascular Imaging (RVI) parameters
Timepoint [2] 298592 0
3 years
Secondary outcome [3] 298607 0
Cognitive decline as defined by a fall in summed average z-scores of >1 SD on any cognitive domain evaluated
Timepoint [3] 298607 0
3 years

Eligibility
Key inclusion criteria
Enrolling into the parent ASPREE study.
Aged 70 and over
Able and willing to provide informed consent
Minimum age
70 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
History of a diagnosed cardiovascular event, including AMI and stroke, atrial fibrillation, serious intercurrent illness likely to cause death within 5 years, cognitive impairment or dementia, disability, anaemia, a current or recurrent condition with a high risk of major bleeding, absolute contraindication or allergy to aspirin.

Also known history of sleep apnoea and/ or current use of continuous positive airways pressure (CPAP) at night

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Enrollment into the parent study ASPREE is through general practitioner co-investigators. Informed consent for participation in ASPREE is obtained by ASPREE research staff. Enrollment into the SNORE-ASA study takes place at the second baseline ASPREE visit, prior to randomisation to either aspirin or placebo in ASPREE.

Randomisation takes place through the parent ASPREE study. All staff remain blinded to treatment allocation through the randomisation procedure.

The randomisation list is generated by an independent statistician using the STATA "ralloc" procedure with randomisation stratified for site and age (<80 yrs and >80 yrs).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation list is generated by an independent statistician using the STATA "ralloc" procedure with randomisation stratified for site and age (<80 yrs and >80 yrs).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Active, not 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)
ACT,NSW,SA,VIC
Recruitment postcode(s) [1] 5582 0
3004

Funding & Sponsors
Funding source category [1] 285748 0
Government body
Name [1] 285748 0
NHMRC
Address [1] 285748 0
Level 1
16 Marcus Clarke Street
Canberra ACT 2601
Country [1] 285748 0
Australia
Primary sponsor type
University
Name
Monash University
Address
ASPREE National Co-ordinating Centre
Department of Epidemiology and Preventive Medicine
Ground Floor, Burnet Building
89 Commercial Rd
Melbourne VIC 3004
Country
Australia
Secondary sponsor category [1] 284609 0
None
Name [1] 284609 0
Address [1] 284609 0
Country [1] 284609 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287754 0
The Alfred Health Human Ethics Committee
Ethics committee address [1] 287754 0
Ethics & Research Governance
Ground Floor, Linay Pavilion
The Alfred Hospital
Commercial Road, Melbourne, 3004
Victoria
Ethics committee country [1] 287754 0
Australia
Date submitted for ethics approval [1] 287754 0
21/11/2011
Approval date [1] 287754 0
30/01/2012
Ethics approval number [1] 287754 0
1/11/0452
Ethics committee name [2] 287755 0
Monash University Human Research Ethics Committee
Ethics committee address [2] 287755 0
First Floor, Building 3e
Monash Research Office
Clayton Campus
Monash University VIC 3800
Victoria
Ethics committee country [2] 287755 0
Australia
Date submitted for ethics approval [2] 287755 0
01/02/2012
Approval date [2] 287755 0
13/02/2012
Ethics approval number [2] 287755 0
CF12/0367
Ethics committee name [3] 296429 0
ACT Health Human Research Ethics Committee
Ethics committee address [3] 296429 0
The Canberra Hospital Building 10 level 6
Yamba Drive Garran ACT 2605
Ethics committee country [3] 296429 0
Australia
Date submitted for ethics approval [3] 296429 0
05/11/2012
Approval date [3] 296429 0
30/11/2012
Ethics approval number [3] 296429 0
10.12.245
Ethics committee name [4] 296430 0
University of Adelaide Human Research Ethics Committee
Ethics committee address [4] 296430 0
The University of Adelaide
South Australia 5005
Ethics committee country [4] 296430 0
Australia
Date submitted for ethics approval [4] 296430 0
01/11/2012
Approval date [4] 296430 0
13/12/2012
Ethics approval number [4] 296430 0
H-2012-162

Summary
Brief summary
Sleep Disordered Breathing (SDB) is very common in older adults. Previous studies have identified that approximately 50% of adults aged 70 and over have some degree of SDB. Obstructive Sleep Apnoea (OSA) is the most common form and refers to intermittent obstructions to airflow during sleep, most often associated with snoring.

While OSA has been shown to be associated with cognitive dysfunction in middle aged adults, the effect of OSA on cognitive outcomes in older adults is less well established, as there have been few prospective studies.

SNORE-ASA will investigate whether sleep apnoea in healthy older adults is associated with cognitive decline over three years of follow-up, and whether daily low dose aspirin is protective against this cognitive decline associated with sleep apnoea. The study will also examine how sleep apnoea may cause cognitive decline in older adults, by using brain MRI and retinal photography to determine whether sleep apnoea causes hypoxaemia-induced small blood vessel flow problems (ischaemia), and whether aspirin alters this process.
Trial website
http://www.aspree.org/AUS/aspree-content/aspree-sub-studies/SNOREASA.aspx
Trial related presentations / publications
Hamilton GS, O'Donoghue FJ. The brain in obstructive sleep apnea: the chickens
coming home to roost? Sleep. 2013 May 1;36(5):637-9. doi: 10.5665/sleep.2616.
PubMed PMID: 23633745; PubMed Central PMCID: PMC3624817.

Conference Oral Presentation, Australia and New Zealand Society of Geriatric Medicine Annual Scientific Meeting June 1-3, 2016 Cairns, Australia.
SA Ward, GS Hamilton, R Woods, MT Naughton, F O’Donoghue, D O’Reilly, JJ McNeil, E Storey. Diagnosing Sleep Disordered Breathing in community dwelling older people: lessons from the SNORE-ASA clinical trial Australasian Journal on Ageing, Vol 35 Supplement S1, June 2016, 18–41

Ward SA, Storey E, Woods RL, Hamilton GS, Kawasaki R, Janke AL, Naughton MT,
O'Donoghue F, Wolfe R, Wong TY, Reid CM, Abhayaratna WP, Stocks N, Trevaks R,
Fitzgerald S, Hodgson LAB, Robman L, Workman B, McNeil JJ; ASPREE Study Group.
The Study of Neurocognitive Outcomes, Radiological and Retinal Effects of Aspirin
in Sleep Apnoea- rationale and methodology of the SNORE-ASA study. Contemp Clin
Trials. 2017 Oct 31. pii: S1551-7144(17)30444-5. doi: 10.1016/j.cct.2017.10.016.
[Epub ahead of print] PubMed PMID: 29097299.
Public notes

Contacts
Principal investigator
Name 34526 0
Prof Elsdon Storey
Address 34526 0
Department of Neuroscience
Alfred Hospital
Commercial Road
Melbourne, VIC
3004
Australia
Country 34526 0
Australia
Phone 34526 0
+61 3 90762552
Fax 34526 0
Email 34526 0
elsdon.storey@monash.edu
Contact person for public queries
Name 17773 0
Dr Dr Stephanie Ward
Address 17773 0
ASPREE National Coordinating Centre
Ground Floor, Burnet Building
89 Commercial Rd
Melbourne 3004
Victoria
Country 17773 0
Australia
Phone 17773 0
1800 728 745
Fax 17773 0
+61 03 9903 0979
Email 17773 0
stephanie.ward@monash.edu
Contact person for scientific queries
Name 8701 0
Dr Dr Stephanie Ward
Address 8701 0
ASPREE National Coordinating Centre
Ground Floor, Burnet Building
89 Commercial Rd
Melbourne 3004
Victoria
Country 8701 0
Australia
Phone 8701 0
1800 728 745
Fax 8701 0
+61 03 9903 0979
Email 8701 0
stephanie.ward@monash.edu

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary