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Trial registered on ANZCTR


Registration number
ACTRN12608000301369
Ethics application status
Approved
Date submitted
3/06/2008
Date registered
17/06/2008
Date last updated
13/10/2011
Type of registration
Retrospectively registered

Titles & IDs
Public title
Metabolic and Neurobiological changes after Continuous Positive Airway Pressure treatment for Obstructive Sleep Apnea
Scientific title
Metabolic and Neurobiological changes after Continuous Positive Airway Pressure (CPAP) treatment for Obstructive Sleep Apnea (OSA)
Secondary ID [1] 253397 0
.
Universal Trial Number (UTN)
Trial acronym
MANPAP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obstructive Sleep Apnea 3223 0
Condition category
Condition code
Respiratory 3388 3388 0 0
Sleep apnoea

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Blinded Continuous Positive Airway Pressure for 12 weeks followed by open-label CPAP treatment for 12 weeks.
The subjects will undergo a 3 night home-titration using an auto-titrating machine. The machine will then be set to the 90th percentile on a fixed pressure for the remainder of the study. We are using an identical Sham machine. A trained CPAP technologist who had been involved in other similar sham-controlled trials is responsible for the allocation of the CPAP machines for this and all other studies. Only this person has access to the sham machines, which she stores separately from the effective CPAP machines. This person will have no direct contact with the subjects.
This is a 24 week study. For the first 12 weeks of the study, Week 0 to Week 12, the subject is randomised to use either therapeutic CPAP or sham CPAP every night for the entire 12 weeks. This first 12 weeks is blinded.
From Week 12 to Week 24 every subject is changed to receive open-label therapeutic CPAP every night for the entire 12 weeks. They will return the blinded machine they used from Week 0 to Week 12 and will receive a new therapeutic machine.
Intervention code [1] 2964 0
Treatment: Devices
Comparator / control treatment
Sham Continuous Positive Airway Pressure
The technical details are propriety and are therefore not available to us. However, this device has been used worldwide as a state of the art sham device and we are currently using this device in a currently approved protocol. In brief, the sham device does not deliver effective pressure to the patient through two mechanisms:
· An internal release valve (inside the machine, so it cannot be detected by the casual observer) releases pressure and hence therapeutic pressure is not delivered to the patient
· A swivel is attached to the CPAP mask, which has an opening through which air escapes which again prevents effective pressure being delivered to the patient.
The pressure delivered by the sham device is actually slightly higher than atmospheric pressure (ie 0.5 cm H2O).
The subjects are randomised to either therapeutic or sham CPAP in the first 12 weeks (Week 0 to Week 12). No matter what machine they are assigned to (they will not be aware as is blinded) they will use the machine every night while sleeping for the entire 12 weeks (Week 0 to Week 12).
At week 12 each subject will return the blinded machine (either sham or therapeutic). Everyone will receive a open-label therapeutic CPAP machine which they will use every night for the entire next 12 weeks (Week12 to Week24)
Control group
Placebo

Outcomes
Primary outcome [1] 4284 0
Change in Abdominal Visceral Fat
Single slice 3D Computerised Tomography (CT) scan of the abdomen. The single slice is taken in relation to a bony landmark (eg T12/L1 or L4/L5 in the axial plane) and hence is reproducible serially.
Timepoint [1] 4284 0
12 weeks after Randomisation
Secondary outcome [1] 7216 0
Change in Total Body Fat and Muscle Mass
- Dexa scan and bioimpedence
Timepoint [1] 7216 0
at 12 weeks after randomisation
Secondary outcome [2] 7217 0
Change in Insulin Sensitivity
- Insulin sensitivity will be assessed by modified minimal model (MINMOD) analysis of multiple measurements of c-peptide (at 0, 10, 20, 30, 60, 90 and 120 after a 75g oral glucose load)
Timepoint [2] 7217 0
at 12 weeks after randomisation
Secondary outcome [3] 7218 0
Change in Arterial Stiffness and Central Blood Pressure
- Peripheral and central blood pressure will be assessed by non-invasive tonometry with a brachial sphymomanometer. This is a measurement of arterial stiffness using pulse wave analysis
Timepoint [3] 7218 0
at 6 and 12 weeks after randomisation
Secondary outcome [4] 7219 0
Change in Physical Activity
- Physical activity and will be assessed by questionnaire (IPAQ) and objective assessment (Actigraphy). The subject will complete a diary containing questions relating to sleep, such as bed time and time of awakening, while undertaking Actigraphy.
Timepoint [4] 7219 0
at 6 and 12 weeks after randomisation
Secondary outcome [5] 7220 0
Change in Blood Hormones
Timepoint [5] 7220 0
at 6 and 12 weeks after randomisation
Secondary outcome [6] 7221 0
Change in sleep and breathing parameters
- Sleep will measured by the gold standard Polysomnograph which requires the attachment of leads to the subject in order to measure chest and abdominal movement, airflow at the mouth and lips, blood oxygen level, muscle tone, eye movements, heart rate and electrical activity in the brain. The subject will be required to sleep with these leads attached. The study is scored using standard criteria.

In addition, a functional assessment of the effects of sleepiness will be used. These are validated questionnaires (FOSQ) which assess the impact of sleepiness on multiple activities of daily living (36). The Epworth Sleepiness Scale and assessment of functional outcomes of sleep and neurocognitive function will also be assessed using a 60 minute computer program performed in conjunction with the sleep study. Other measures of sleep at each visit are validated questionnaires and tests (Functional Outcomes of Sleep, Sleepiness scales, driving simulation test).
Timepoint [6] 7221 0
at 6 and 12 weeks after randomisation
Secondary outcome [7] 273243 0
Change in vascular reactivity and repair (as measure by peripheral arterial tonometry (PAT) and endothelial progenitor cell counts)
Timepoint [7] 273243 0
at 12 weeks after randomisation
Secondary outcome [8] 273244 0
Change in Bone Turnover Markers (Osteocalcin, CTX, P1NP, Vitmain D and PTH) and Renal Function (urinary albumin) (blood and urine)
Timepoint [8] 273244 0
at 6 and 12 weeks after randomisation
Secondary outcome [9] 273245 0
Change in Erectile Dysfunction as measured by the modified International Index of Erectile Function (IIEF) and an erectile function survey (EFS).
Timepoint [9] 273245 0
at 6 and 12 weeks after randomisation
Secondary outcome [10] 273246 0
Change in abdominal subcutaneous fat Single slice 3D Computerised Tomography (CT) scan of the abdomen. The single slice is taken in relation to a bony landmark (eg T12/L1 or L4/L5 in the axial plane) and hence is reproducible serially.
Timepoint [10] 273246 0
at 12 weeks after randomisation
Secondary outcome [11] 273247 0
Change in Anthropometry measurements (weight, height and waist, neck, hip, mid-arm and mid-thigh circumferences)
Timepoint [11] 273247 0
at 6 and 12 weeks after randomisation
Secondary outcome [12] 273248 0
TERTIARY OUTCOME: All the above measured outcomes during the open-label CPAP period (12-24 weeks after randomisation)
Timepoint [12] 273248 0
at 24 weeks after randomisation (if collected only at 12 weeks)
at 18 and 24 weeks (if collected at 6 and 12 weeks)
except for vascular reactivity and repair which were not collected during the open-label period.

Eligibility
Key inclusion criteria
1. Males aged 18 years or above.
2. Moderate to severe obstructive sleep apnea with respiratory disturbance Index (RDI) =20/hr and inclusive of =3% desaturation (RDI >=20 and ODI >=15)
3. Written informed consent
4. Good general health as defined as men who are community dwelling, with no significant uncontrolled medical problems who are independent in activities of daily living.
5. Medical history and physical examination indicating no clinical evidence for significant and uncontrolled cardiovascular (ischemic, hypertension), diabetes, renal, liver, prostate or any other disease.
Minimum age
18 Years
Maximum age
No limit
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
1. Severe OSA (minimum oxygen saturation < 65% or RDI > 80) requiring immediate treatment due to severity or increased associated risk (eg Transport worker)
2. Psychiatric disorders or drug abuse unless well controlled
3. Chronic medical conditions likely to interfere with or influence study treatment or safety unless well controlled
4. Contradictions to CPAP therapy
5. Any other condition likely, in the judgment of the investigator, that makes the patient unable to complete safely, or otherwise unsuitable for the study
6. Shift workers

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
After written consent patients will be enrolled in a randomised order sham-controlled crossover double blind study. At the end of the baseline visit patients will be randomly assigned, by equal chance, to either CPAP or Sham-CPAP (1:1 basis) for 12 weeks. All patients will then receive 12-weeks open-label therapeutic CPAP.
A separate co-ordinator will be responsible for the allocation of machines and will have no direct contact with the subjects. The sham devices are identical in appearance to commercially available therapeutic CPAP equipment which will ensure blinding.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation by using a randomisation table created by computer software (i.e., computerised sequence generation).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis

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 in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 3447 0
Government body
Name [1] 3447 0
National Health and Medical Research Council (NHMRC)
Address [1] 3447 0
GPO Box 1421
Canberra ACT 2601
Country [1] 3447 0
Australia
Primary sponsor type
Hospital
Name
Sydney South West Area Health Service
Address
Royal Prince Alfred Hospital, Missenden Road, Camperdown, NSW, 2050
Country
Australia
Secondary sponsor category [1] 3090 0
Charities/Societies/Foundations
Name [1] 3090 0
Woolcock Institute of Medical Research
Address [1] 3090 0
431 Glebe Point Rd Glebe
Country [1] 3090 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 5474 0
Sydney South West Area Health Services (SSWAHS) Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 5474 0
c/- Research Development Office
Level 8, Building 14
Royal Prince Alfred Hospital
Missenden Road
CAMPERDOWN NSW 2050
Ethics committee country [1] 5474 0
Australia
Date submitted for ethics approval [1] 5474 0
Approval date [1] 5474 0
Ethics approval number [1] 5474 0
X08-0043

Summary
Brief summary
This study is designed to investigate nasal Continuous Positive Airway Pressure (CPAP) therapy’s efficacy to improve important intermediate markers of cardio-metabolic health (visceral fat, insulin sensitivity, central blood pressure, arterial stiffness).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 28640 0
Address 28640 0
Country 28640 0
Phone 28640 0
Fax 28640 0
Email 28640 0
Contact person for public queries
Name 11797 0
Camilla Hoyos
Address 11797 0
Woolcock Institute of Medical Research, PO Box M77, Missenden Rd, Camperdown, NSW, 2050
Country 11797 0
Australia
Phone 11797 0
+61 2 9114 0449
Fax 11797 0
+61 2 9114 0014
Email 11797 0
camillah@woolcock.org.au
Contact person for scientific queries
Name 2725 0
A/Prof Peter Liu
Address 2725 0
Woolcock Institute of Medical Research, PO Box M77, Missenden Rd, Camperdown, NSW, 2050
Country 2725 0
Australia
Phone 2725 0
+61 2 9114 0459
Fax 2725 0
+61 2 9114 0014
Email 2725 0
pliu@mail.usyd.edu.au

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