Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618000904279
Ethics application status
Approved
Date submitted
23/05/2018
Date registered
29/05/2018
Date last updated
28/09/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Linking Brain Vascular Function with Neurobehavioral Function in Obstructive Sleep Apnoea
Scientific title
The effects of continuous positive airway pressure (CPAP) treatment for obstructive sleep apnoea (OSA) on cerebrovascular and neurobehavioral function
Secondary ID [1] 294642 0
None
Universal Trial Number (UTN)
U1111-1214-4491
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
obstructive sleep apnoea 307957 0
Condition category
Condition code
Respiratory 306992 306992 0 0
Sleep apnoea

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Continuous positive airway pressure (CPAP)
This is routine gold-standard treatment.
Participants will have an in-lab CPAP titration study with pressure adjustment by trained sleep technologist. The delivered pressure will be determined by the CPAP titration study. Mask fitting and CPAP education will also be provided by trained sleep technologist. A loan CPAP machine (Resmed S8 or Phillips REMSTAR) will be provided on loan for participant use.
After starting therapy, the participant will be asked to return at 2 weeks for a device download and any required trouble shooting as well as at 6 weeks if required. Participants will use their CPAP machine for a total of 3 months treatment period prior to re-testing. The CPAP machine data will be recorded at 2 weeks and end of 3 months therapy. This will include data on CPAP adherence throughout the 3 months period.
Intervention code [1] 301286 0
Treatment: Devices
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 305978 0
Change in brain tissue oxygen saturation during a hypoxaemic challenge after CPAP treatment relative to baseline This will be using near infrared spectroscopy where dynamic regional cerebral tissue oxygenation can be measured (ScO2).

Details of ventilatory maneouvres in hypoxaemic challenge:
The ventilatory maneouvres will involve participants breathing through a breathing circuit of three different pre-determined gas mixture, producing hypoxic hypercapnia, hyperoxic hypercapnia and isocapnia hypoxia during wakefulness. These tests will be terminated at 5 minutes or SpO2 <80%, EtCO2> 10%.
During these challenges, their cerebral oxygenation will be measured by near-infrared spectroscopy and blood pressure and arterial waveform recorded using a beat-to-beat finger blood pressure device.
The duration of each challenge is 5 minutes with 15 minute break between each test. This will be performed by clinicians/scientists who are trained in this technique in a controlled hospital environment. These sets of challenges will be performed after the initial overnight sleep study (prior to CPAP therapy) and repeated at the end of the CPAP treatment period for comparison. Both pre- and post- CPAP therapy challenge sets will be conducted at a similar time for each patient for consistency.
Timepoint [1] 305978 0
3 months post-intervention commencement
Secondary outcome [1] 347165 0
Change in multi-domain neurobehavioral performance after CPAP treatment relative to baseline:
- Psychomotor vigilance test
Timepoint [1] 347165 0
3 months post-intervention commencement
Secondary outcome [2] 347166 0
Change in multi-domain neurobehavioral performance after CPAP treatment relative to baseline:
- N-back test
Timepoint [2] 347166 0
3 months post-intervention commencement
Secondary outcome [3] 347167 0
Change in multi-domain neurobehavioral performance after CPAP treatment relative to baseline:
- The Stroop Task
Timepoint [3] 347167 0
3 months post-intervention commencement
Secondary outcome [4] 347168 0
Change in multi-domain neurobehavioral performance after CPAP treatment relative to baseline
- Letter Cancellation Task
Timepoint [4] 347168 0
3 months post-intervention commencement
Secondary outcome [5] 347169 0
Change in multi-domain neurobehavioral performance after CPAP treatment relative to baseline
- AusEd driving simulation
Timepoint [5] 347169 0
3 months post-intervention commencement
Secondary outcome [6] 347170 0
Change in multi-domain neurobehavioral performance after CPAP treatment relative to baseline
- Karolinska Drowsiness Test with high-density EEG
Timepoint [6] 347170 0
3 months post-intervention commencement
Secondary outcome [7] 347171 0
Change in declarative memory test (using word-pairs task) after CPAP treatment relative to baseline
Timepoint [7] 347171 0
3 months post-intervention commencement
Secondary outcome [8] 347172 0
Change in procedural memory test (using finger tapping motor task) after CPAP treatment relative to baseline
Timepoint [8] 347172 0
3 months post-intervention commencement
Secondary outcome [9] 347177 0
Change in self reported mood using Hospital Anxiety Depression Score after CPAP treatment relative to baseline
Timepoint [9] 347177 0
3 months post-intervention commencement
Secondary outcome [10] 347178 0
Change in sleep ratings after CPAP treatment relative to baseline:
- The Epworth Sleepiness Scale (ESS)
Timepoint [10] 347178 0
3 months post-intervention commencement
Secondary outcome [11] 347179 0
Change in sleep ratings after CPAP treatment relative to baseline:
- Insomnia Severity Index (ISI)
Timepoint [11] 347179 0
3 months post-intervention commencement
Secondary outcome [12] 347180 0
Change in sleep ratings after CPAP treatment relative to baseline:
- Karolinska Sleepiness Scale (KSS)
Timepoint [12] 347180 0
3 months post-intervention commencement
Secondary outcome [13] 347181 0
Change in multi-domain neurobehavioral performance after CPAP treatment relative to baseline
- Weshsler Test of Adult Reading (WTAR)
Timepoint [13] 347181 0
3 months post-intervention commencement
Secondary outcome [14] 347182 0
Change in arterial stiffness (using pulse wave analysis) during a hypoxaemic challenge after CPAP treatment relative to baseline

Details of ventilatory maneouvres in hypoxaemic challenge:
The ventilatory maneouvres will involve participants breathing through a breathing circuit of three different pre-determined gas mixture, producing hypoxic hypercapnia, hyperoxic hypercapnia and isocapnia hypoxia during wakefulness. These tests will be terminated at 5 minutes or SpO2 <80%, EtCO2> 10%.
During these challenges, their cerebral oxygenation will be measured by near-infrared spectroscopy and blood pressure and arterial waveform recorded using a beat-to-beat finger blood pressure device.
The duration of each challenge is 5 minutes with 15 minute break between each test. This will be performed by clinicians/scientists who are trained in this technique in a controlled hospital environment. These sets of challenges will be performed after the initial overnight sleep study (prior to CPAP therapy) and repeated at the end of the CPAP treatment period for comparison. Both pre- and post- CPAP therapy challenge sets will be conducted at a similar time for each patient for consistency.
Timepoint [14] 347182 0
3 months post-intervention commencement
Secondary outcome [15] 347183 0
Change in brain amyloid-B after CPAP treatment relative to baseline
This will be measured using MRI utilising phase difference enhanced imaging (PADRE)
Timepoint [15] 347183 0
3 months post-intervention commencement
Secondary outcome [16] 347203 0
Change in brain tissue oxygen saturation (measured by near-infrared spectroscopy) during overnight polysomnogram after CPAP treatment relative to baseline
Timepoint [16] 347203 0
3 months post-intervention commencement

Eligibility
Key inclusion criteria
• PSG confirmed ODI >/= 15 and AHI >/= 30 with a diagnosis of moderate-severe hypoxemic OSA;
• Recommended for CPAP treatment by the attending sleep physician
• Ability to perform neurobehavioral tests;
• Able to give informed consent;
• Fluent in English.
Minimum age
20 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Clinically significant co-morbidity;
• History of head injury or psychiatric/neurological disorder (including stroke);
• Use of CNS active agents;
• Heavy alcohol consumption (40g daily);
• Current shift-worker or travelled overseas within the last 2 weeks;
• Previously used CPAP;
• Excessive symptoms and/or very severe OSA which in the opinion of the treating physician requires urgent CPAP treatment

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
Brain tissue oxygenation, arterial stiffness, performance on neurobehavioral and memory tasks, and questionnaire responses before and after CPAP therapy will be compared using paired t-tests.
The association between brain tissue oxygenation, arterial stiffness and neurobehavioral performance will be explored using multiple linear regression.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/11/2018
Actual
Date of last participant enrolment
Anticipated
3/07/2020
Actual
Date of last data collection
Anticipated
2/10/2020
Actual
Sample size
Target
33
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 10956 0
Woolcock Institute of Medical Research - Glebe
Recruitment postcode(s) [1] 22742 0
2037 - Glebe

Funding & Sponsors
Funding source category [1] 299259 0
University
Name [1] 299259 0
Centre for Integrated Research and Understanding of Sleep (CIRUS)
Country [1] 299259 0
Australia
Primary sponsor type
Individual
Name
Craig Phillips
Address
Woolcock Institute of Medical Research
431 Glebe Point Rd, Glebe NSW 2037
Country
Australia
Secondary sponsor category [1] 298853 0
Other Collaborative groups
Name [1] 298853 0
Woolcock Institute of Medical Research
Address [1] 298853 0
431 Glebe Point Rd, Glebe NSW 2037
Country [1] 298853 0
Australia
Other collaborator category [1] 280120 0
Other Collaborative groups
Name [1] 280120 0
Neuroscience Research Australia Imaging Centre
Address [1] 280120 0
Barker St, Randwick NSW 2031
Country [1] 280120 0
Australia
Other collaborator category [2] 280121 0
Hospital
Name [2] 280121 0
Royal Prince Alfred Hospital
Address [2] 280121 0
Missenden Road
CAMPERDOWN NSW 2050
Country [2] 280121 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300176 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 300176 0
Research Ethics and Governance Office (REGO) Royal Prince Alfred Hospital Missenden Road Camperdown NSW 2050
Ethics committee country [1] 300176 0
Australia
Date submitted for ethics approval [1] 300176 0
18/06/2018
Approval date [1] 300176 0
17/08/2018
Ethics approval number [1] 300176 0

Summary
Brief summary
Obstructive sleep apnoea (OSA) is a condition in which the upper airway collapses during sleep, leading to episodes of sleep fragmentation and hypoxemia. OSA has been linked to a decrease in neurocognitive function in some patients and potentially to the development of dementia, however the mechanisms remain unclear.
This clinical study will investigate the link(s) between cerebrovascular response to hypoxemia, arterial stiffness, brain tissue hypoxia and neurocognitive function in OSA patients, before and after 8 weeks of CPAP treatment.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 2736 2736 0 0
/AnzctrAttachments/374935-Protocol 180510_CP (1).pdf (Protocol)

Contacts
Principal investigator
Name 82798 0
A/Prof Craig Phillips
Address 82798 0
Woolcock Institute of Medical Research
431 Glebe Point Rd, Glebe NSW 2037
Country 82798 0
Australia
Phone 82798 0
+61 2 9463 2936
Fax 82798 0
Email 82798 0
craig.phillips@sydney.edu.au
Contact person for public queries
Name 82799 0
A/Prof Craig Phillips
Address 82799 0
Woolcock Institute of Medical Research
431 Glebe Point Rd, Glebe NSW 2037
Country 82799 0
Australia
Phone 82799 0
+61 2 9463 2936
Fax 82799 0
Email 82799 0
craig.phillips@sydney.edu.au
Contact person for scientific queries
Name 82800 0
A/Prof Craig Phillips
Address 82800 0
Woolcock Institute of Medical Research
431 Glebe Point Rd, Glebe NSW 2037
Country 82800 0
Australia
Phone 82800 0
+61 2 9463 2936
Fax 82800 0
Email 82800 0
craig.phillips@sydney.edu.au

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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Documents added automatically
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