Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620000694910
Ethics application status
Approved
Date submitted
8/05/2020
Date registered
22/06/2020
Date last updated
22/06/2020
Date data sharing statement initially provided
22/06/2020
Date results provided
22/06/2020
Type of registration
Retrospectively registered

Titles & IDs
Public title
Microvascular and Macrovascular Disease in Snoring and Obstructive Sleep Apnoea
Scientific title
Microvascular and Macrovascular Disease in Snoring and Obstructive Sleep Apnoea: A Mechanism for Increased Stroke Risk
Secondary ID [1] 301212 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obstructive Sleep Apnoea 317357 0
Stroke 317577 0
Condition category
Condition code
Respiratory 315464 315464 0 0
Sleep apnoea
Stroke 315663 315663 0 0
Ischaemic
Stroke 315826 315826 0 0
Haemorrhagic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants are assigned to this health-related intervention for this study.

Project 1 (main study)
Overall duration of Project 1 is single observation. A Sleep technician will administer the treatment and the duration of each is 12 hours starting at 6pm.

Baseline: Clinic visit consultation with respiratory physician-
• Anthropometry data including age, gender, body mass index, waist-hip ratio, neck circumference
• Questionnaire data including cardiovascular risk (Framingham questionnaire); Epworth Sleepiness Scale (ESS)
• Snoring and smoking history
• Detailed history of hypertension including length of known diagnosis and current treatment.
• Fasting blood sample for lipid profile and glucose level (am)
• Polysomnography (PSG) including supine blood pressure before and after sleep and recording snoring sounds conducted at Sleep Laboratory, Westmead Hospital - administered by the sleep technician
• Carotid Artery Ultrasound - both carotid arteries will be used to measure intima-media thickness (IMT) of the common carotid, plaque type and extent, lumen diameter, and peak systolic velocity conduced before sleep study (pm) at Westmead Hospital - administered by the researcher
• Digital retinal photography (am and pm) where both eyes will be graded for retinal microvascular lesions using standard protocol under direction of Centre for Vision Research (Westmead Institute for Medical Research) conducted at Westmead Hospital

Project 2 (sub-study)
Overall duration of Project 2 (sub-study) is 12 months. Participants with moderate-severe OSA who attended a sleep clinic will be enrolled into the sub-study. A Sleep technician will administer the treatment and the duration of each visit is 12 hours starting at 6pm.

4 weeks after Baseline visit in Project 1 (Run-in/Week -4): clinic visit consultation with respiratory physician-
• Medication review, weight, waist-hip ratio, neck circumference, blood pressure, questionnaire data including cardiovascular risk (Framingham questionnaire); Epworth Sleepiness Scale (ESS)

4 weeks after Run-in (Baseline/Week 0) (sub-study):
• Polysomnography (PSG) including supine blood pressure before and after sleep and recording snoring sounds conducted at Sleep Laboratory, Westmead Hospital - administered by the sleep technician
• Fasting blood sample for lipid profile and glucose level (am)
• Carotid Artery Ultrasound - both carotid arteries will be used to measure intima-media thickness (IMT) of the common carotid, plaque type and extent, lumen diameter, and peak systolic velocity conduced before sleep study (pm) at Westmead Hospital - administered by the researcher
• Digital retinal photography (am and pm) where both eyes will be graded for retinal microvascular lesions using standard protocol under direction of Centre for Vision Research (Westmead Institute for Medical Research) conducted at Westmead Hospital

1 week after Baseline (CPAP titration/Week 1) (sub-study):
• Polysomnography (PSG) – CPAP titration study to eliminate snoring and obstructive events as per laborabory protocol at Westmead Hospital Sleep Laboratory - administered by the sleep technician

Week 26 and 52 (sub-study):
• Polysomnography (PSG) – CPAP titration study including, weight, supine blood pressure before and after sleep conducted at Sleep Laboratory, Westmead Hospital - administered by the sleep technicialn
• Fasting blood sample for lipid profile and glucose level (am)
• Carotid Artery Ultrasound - both carotid arteries will be used to measure intima-media thickness (IMT) of the common carotid, plaque type and extent, lumen diameter, and peak systolic velocity conduced before sleep study (pm) at Westmead Hospital - administered by the researcher
• Digital retinal photography (am and pm) where both eyes will be graded for retinal microvascular lesions using standard protocol under direction of Centre for Vision Research (Westmead Institute for Medical Research) conducted at Westmead Hospital

A brief description of a polysomnography and CPAP titration:
Overnight in-laboratory sleep study with monitoring of breathing (nasal pressure, inductive plethysmography), blood oxy-haemoglobin saturation, and sleep stage (electro-encephalogram). For CPAP titration the patient wears a mask to which positive pressure is applied. With the patient asleep the sleep technician adjusts the level of pressure applied until sleep disordered breathing is eliminated. This level of pressure is then established as the prescribed pressure to be set on the CPAP device for use by the patient at home.
Intervention code [1] 317510 0
Treatment: Devices
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 323706 0
Project 1 -
Primary Outcome 1: Intima-media thickness
Method of Assessment: Ultrasound examination of carotid and femoral arteries
Timepoint [1] 323706 0
Project 1 -
Primary outcome 1 timepoint: Baseline
Primary outcome [2] 323707 0
Project 1 -
Primary Outcome 2: Retinal vessel diameter
Method of Assessment: Digital retinal photographs, sleep disordered breathing assessed by polysomnography

Please note that that sleep disordered breathing is not an outcome. It is a descriptor of participant status in the same way that age, BMI etc are
Timepoint [2] 323707 0
Project 1 -
Primary outcome 2 timepoint: Baseline; PM and AM retinal photographs taken at initial (baseline) overnight sleep study
Primary outcome [3] 324026 0
Project 2 (sub-study) -
Primary outcome 1: Change in Intima-media thickness
Method of Assessment: Ultrasound examination of carotid and femoral arteries
Timepoint [3] 324026 0
Project 2 (sub-study) -
Primary outcome 1 timepoint: Baseline; Week 26 and Week 52 (primary timepoint)
Secondary outcome [1] 382679 0
Project 2 (sub-study) -
Primary outcome 2: Change in Retinal vessel diameter
Method of Assessment: Digital retinal photographs, sleep disordered breathing assessed by polysomnography

Please note that that sleep disordered breathing is not an outcome. It is a descriptor of participant status in the same way that age, BMI etc are
Timepoint [1] 382679 0
Project 2 (sub-study) -
Primary outcome 2 timepoint: Baseline; PM and AM retinal photographs taken at initial (baseline) overnight sleep study
Secondary outcome [2] 383588 0
Project 1 -
Secondary Outcome: Identification of retinal vessel emboli
Method of Assessment: Retinal photographs before and after sleep
Timepoint [2] 383588 0
Time points: Baseline- PM and AM retinal photographs taken at initial (baseline) overnight sleep study

Eligibility
Key inclusion criteria
Project 1
1. Over 45 years old
2. Have a diagnostic sleep study referral for obstructive sleep apnoea

Project 2
1. Completed Project 1
2. Diagnosis of severe, symptomatic OSAS (RDI greater than or equal to 30 events/hour, ESS greater than 9)
Minimum age
45 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Project 1
1. Past history of stroke, diabetes, atrial fibrillation, congestive cardiac failure, carotid artery surgery
2. Eye pathologies that preclude the measurement of retinal vessel calibre (e.g. age-related macular degeneration, glaucoma

Project 2
1. As for Project 1
2. Current smoker
3. Inability to tolerate CPAP therapy

Study design
Purpose of the study
Treatment
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
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Project 1
Univariate relationships between measures of OSAS or snoring severity (AHI, Arousal Index, Oxygen Desaturation Index, snore index) independently examined using linear regression analysis for continuous data and X2 analysis for categorical data. Stepwise multiple linear regression or logistic regression will be used to examine associations of OSAS and snoring (continuous data) with dependent variables, including any interactions with anthropometric and vascular risk factor data. From the preliminary data, a sample size of 384 for the cohort study will have 80% power to detect a difference in the CRVE means of 8.0µm (and difference in CRAE means of 13.6µm), assuming that the common standard deviation is 24.1µm for CRVE and 13.6µm for CRAE, using a two group t-test with two sided significance of p=0.017. For the overnight changes, a sample size of 146 will have 80% power to detect a correlation co-efficient of 0.25 between AVR and snoring using linear regression, assuming normal distribution of AVR and a two sided significance level of p=0.025. Power estimates are conservative based on the dependent variables with the smallest detected signals from our preliminary retinal data.

Project 2
Power analysis is based on data relating to the observed reduction in IMT during CPAP therapy. Power calculations show that with a sample size of 64 we will have 80% power to detect a difference in IMT of 0.025 mm over 12 month, assuming that the common standard deviation is 0.050 mm and using a two group t-test with a 0.05 two-sided significance level. Given the demonstration reduction in IMT of 9% (0.063 mm) in 24 patients over only four months of CPAP treatment, we believe that our power calculation is quite conservative, and that our sample size is robust. Similarly, following 12 months of treatment for hypertension, there have been demonstrated improvements in retinal vessel diameter of 12.5%, consistent with the changes in IMT. We will study 80 subjects to allow for a 20% drop-out rate.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
2/10/2012
Date of last participant enrolment
Anticipated
Actual
25/07/2016
Date of last data collection
Anticipated
Actual
6/12/2016
Sample size
Target
390
Accrual to date
Final
278
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 16609 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 30205 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 305659 0
Government body
Name [1] 305659 0
NHMRC
Country [1] 305659 0
Australia
Primary sponsor type
Individual
Name
Prof John Wheatley
Address
Westmead Hospital
Dept Respiratory and Sleep Medicine
Cnr Hawkesbury and Darcy Rd
Westmead NSW 2145
Country
Australia
Secondary sponsor category [1] 306069 0
None
Name [1] 306069 0
Address [1] 306069 0
Country [1] 306069 0
Other collaborator category [1] 281301 0
Individual
Name [1] 281301 0
Prof Jie Jin Wang
Address [1] 281301 0
Westmead Hospital
Cnr Hawkesbury and Darcy Rd
Westmead NSW 2145
Country [1] 281301 0
Australia
Other collaborator category [2] 281302 0
Individual
Name [2] 281302 0
A/Prof Terence Amis
Address [2] 281302 0
Westmead Hospital
Cnr Hawkesbury and Darcy Rd
Westmead NSW 2145
Country [2] 281302 0
Australia
Other collaborator category [3] 281303 0
Individual
Name [3] 281303 0
A/Prof Kristina Kairaitis
Address [3] 281303 0
Westmead Hospital
Cnr Hawkesbury and Darcy Rd
Westmead NSW 2145
Country [3] 281303 0
Australia
Other collaborator category [4] 281304 0
Individual
Name [4] 281304 0
Prof Richard Lindley
Address [4] 281304 0
Westmead Hospital
Cnr Hawkesbury and Darcy Rd
Westmead NSW 2145
Country [4] 281304 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305943 0
Western Sydney Local Health District HREC
Ethics committee address [1] 305943 0
Ethics committee country [1] 305943 0
Australia
Date submitted for ethics approval [1] 305943 0
16/11/2011
Approval date [1] 305943 0
10/01/2012
Ethics approval number [1] 305943 0
HREC/11/WMEAD/296 (3427)

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 102154 0
Prof John Wheatley
Address 102154 0
Westmead Hospital
Dept Respiratory and Sleep Medicine
Cnr Hawkesbury and Darcy Rd
Westmead NSW 2145
Country 102154 0
Australia
Phone 102154 0
+61 2 8890 6797
Fax 102154 0
+61 2 8890 7286
Email 102154 0
[email protected]
Contact person for public queries
Name 102155 0
John Wheatley
Address 102155 0
Westmead Hospital
Dept Respiratory and Sleep Medicine
Cnr Hawkesbury and Darcy Rd
Westmead NSW 2145
Country 102155 0
Australia
Phone 102155 0
+61 2 8890 6797
Fax 102155 0
+61 2 8890 7286
Email 102155 0
[email protected]
Contact person for scientific queries
Name 102156 0
John Wheatley
Address 102156 0
Westmead Hospital
Dept Respiratory and Sleep Medicine
Cnr Hawkesbury and Darcy Rd
Westmead NSW 2145
Country 102156 0
Australia
Phone 102156 0
+61 2 8890 6797
Fax 102156 0
+61 2 8890 7286
Email 102156 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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
SourceTitleYear of PublicationDOI
Dimensions AISleep disordered breathing has minimal association with retinal microvascular diameters in a non-diabetic sleep clinic cohort2023https://doi.org/10.1371/journal.pone.0279306
N.B. These documents automatically identified may not have been verified by the study sponsor.