Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617000823370
Ethics application status
Approved
Date submitted
24/05/2017
Date registered
6/06/2017
Date last updated
15/03/2021
Date data sharing statement initially provided
16/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Health effects of treating sleep apnoea with Continuous Positive Airway Pressure (CPAP) during weight loss in people with pre-diabetes, sleep apnoea and obesity.
Scientific title
Cardio-metabolic health effects of CPAP treatment for sleep apnoea during weight loss: A Randomised Controlled Pilot Trial
Secondary ID [1] 291506 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obstructive sleep apnoea 302583 0
Pre-diabetes 302584 0
obesity 303165 0
Condition category
Condition code
Respiratory 302109 302109 0 0
Sleep apnoea
Diet and Nutrition 302110 302110 0 0
Obesity
Metabolic and Endocrine 302111 302111 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intervention: CPAP with a Weight Loss Program

CPAP:
Participants assigned to the intervention group will be provided with a CPAP machine that with automatically titrate a therapeutic pressure. Prior to commencing CPAP the participants will receive CPAP education and undergo a mask fitting with a CPAP therapist. Participants will be issued with a CPAP and mask to use all night during sleep at home for the three months of the trial. Participants will have 2 pre-arranged consultations (face-to-face or by telephone) for approximately 20 minutes at 2 weeks and 1 month to assist with the initial use of CPAP. Participants can also request additional consultations (as required) with the CPAP therapist to assist with ongoing use of the CPAP device.

Weight Loss and Maintenance Program:
Participants in the intervention group will also receive support with a Weight Loss and Maintenance Program administered by the study dietitian. The patients will receive a lifestyle consultation by phone call from the dietitian at 1 and 2 week time points. Participants will also attend the Woolcock Institute to participate in individual face-to-face lifestyle consultations conducted by the dietitian running for 1-1.5 hours at 1 and 2 months. Participants will also be invited to participate in optional weight maintenance support from the three month time point until the 12 month time point. The weight maintenance support appointments will involve a phone call at 5 and 7 months and a face-to-face consultation at 9 and 12 months. Participants will be asked to document diet, exercise, and sleep habits daily at periods during the trial. They will also be asked to complete a 4-day food diary at 0, 5 and 12 months. 24-hr food recall will also be undertaken at 0 weeks, then at 1, 2, 3, 7 and 9 months to confirm dietary compliance.

Dietary program during the weight maintenance phase:
Total daily energy intakes will be prescribed according to participants’ energy requirements, as estimated using the Harris-Benedict equation with an appropriate activity factor (it is suggested all activity be underestimated to ensure a conservative approach) and 2000kJ/500calorie /day energy deficit to encourage weight loss. Four levels of daily energy will be used in this study (5,7, 9 or 11 MJ/day) and participants will be prescribed an energy level which is closest to their energy intakes as calculated above.

Desired macronutrient distribution will comprise 45% daily energy intake from carbohydrate, 25% from protein, 30% from fat and <1% from alcohol. The diet will aim to be as low in GI as practical and achieved by replacing higher GI carbohydrates with lower GI carbohydrates.

Exercise program during weight loss and weight maintenance phases:
Participants will be provided a safe, tailored exercise prescription with consideration of existing comorbidities or musculoskeletal limitations. The frequency, intensity and volume of exercise will be tailored according to the following progressive targets based on the Australian Physical Activity Guidelines for the general population and the American College of Sports Medicine (ACSM) guidelines for clinically significant weight loss:
1. Commencing with: at least 150 minutes per week of moderate intensity activity, i.e. 30 minutes on most days (Australian Physical Activity Guidelines for the general population)
2. Increasing to: at least 250 minutes per week of moderate intensity cardio exercise, i.e. 45-60 minutes most days (ACSM guidelines for clinically significant weight loss)
3. Plus: at least 1 session per week of ~20-45 minutes strength training
4. Increasing to: 2 times per week.
(48-72 hours recovery between strength training sessions)
5. Plus: flexibility

Lifestyle counselling:
Individual dietary counselling is necessary to identify current dietary patterns, recommend specific changes, and identify barriers and target behavioural change strategies to the individual successfully. Sessions will consist of a combination of diet and exercise reinforcement and will provide the opportunity to progress exercise prescriptions as well as monitor dietary compliance. Health coaching techniques will support behaviour change and techniques are based on the Health Coaching Australia techniques in which the study clinicians are trained.

Written materials:
Participants will be provided with written educational materials that outline their dietary and exercise prescription including the food amounts that constitute one serving and the carbohydrate options and safe/sustainable dietary and exercise recommendations to support weight loss and maintenance.
Intervention code [1] 297577 0
Treatment: Devices
Comparator / control treatment
Control: Weight Maintenance Program alone

Weight Loss and Maintenance Program:
Participants in the control group will receive support with a Weight Loss and Maintenance Program administered by the study dietitian. The patients will receive a lifestyle consultation by phone call from the dietitian at 1 and 2 week time points. Participants will also attend the Woolcock Institute to participate in individual face-to-face lifestyle consultations conducted by the dietitian running for 1-1.5 hours at 1 and 2 months. Participants will also be invited to participate in optional weight maintenance support from the three month time point until the 12 month time point. The weight maintenance support appointments will involve a phone call at 5 and 7 months and a face-to-face consultation at 9 and 12 months. Participants will be asked to document diet, exercise, and sleep habits daily at periods during the trial. They will also be asked to complete a 4-day food diary at 0, 3 and 12 months. 24-hr food recall will also be undertaken at 0 weeks, then at 2, 3, 5 and 7 months to confirm dietary compliance.

Dietary program during the weight maintenance phase:
Total daily energy intakes will be prescribed according to participants’ energy requirements, as estimated using the Harris-Benedict equation with an appropriate activity factor (it is suggested all activity be underestimated to ensure a conservative approach) and 2000kJ/500calorie /day energy deficit to encourage weight loss. Four levels of daily energy will be used in this study (5,7,9 or 11 MJ/day) and participants will be prescribed an energy level which is closest to their energy intakes as calculated above.

Desired macronutrient distribution will comprise 45% daily energy intake from carbohydrate, 25% from protein, 30% from fat and <1% from alcohol. The diet will aim to be as low in GI as practical and achieved by replacing higher GI carbohydrates with lower GI carbohydrates.

Exercise program during weight loss and maintenance phases:
Participants will be provided a safe, tailored exercise prescription with consideration of existing comorbidities or musculoskeletal limitations. The frequency, intensity and volume of exercise will be tailored according to the following progressive targets based on the Australian Physical Activity Guidelines for the general population and the American College of Sports Medicine (ACSM) guidelines for clinically significant weight loss:
1. Commencing with: at least 150 minutes per week of moderate intensity activity, i.e. 30 minutes on most days (Australian Physical Activity Guidelines for the general population)
2. Increasing to: at least 250 minutes per week of moderate intensity cardio exercise, i.e. 45-60 minutes most days (ACSM guidelines for clinically significant weight loss)
3. Plus: at least 1 session per week of ~20-45 minutes strength training
4. Increasing to: 2 times per week.
(48-72 hours recovery between strength training sessions)
5. Plus: flexibility

Lifestyle counselling:
Individual dietary counselling is necessary to identify current dietary patterns, recommend specific changes, and identify barriers and target behavioural change strategies to the individual successfully. Sessions will consist of a combination of diet and exercise reinforcement and will provide the opportunity to progress exercise prescriptions as well as monitor dietary compliance. Health coaching techniques will support behaviour change and techniques are based on the Health Coaching Australia techniques in which the study clinicians are trained.

Written materials:
Participants will be provided with written educational materials that outline their dietary and exercise prescription including the food amounts that constitute one serving and the carbohydrate options and safe/sustainable dietary and exercise recommendations to support weight loss and maintenance.

Optional CPAP trial in follow up period:
Participants in the control group will be offered free CPAP therapy for three months and free CPAP support for nine months following the initial three month randomised controlled period.
Control group
Active

Outcomes
Primary outcome [1] 301646 0
Glucose tolerance, as measured by two hour blood glucose level following an oral glucose tolerance test
Timepoint [1] 301646 0
Measured at Baseline, 3 months primary end point and at 12 months
Secondary outcome [1] 333427 0
Abdominal fat, as measured by dual-energy X-ray absorptiometry (DXA)
Timepoint [1] 333427 0
Measured at Baseline, 3 months and 12 months
Secondary outcome [2] 333428 0
Office Blood pressure, as measured by digital sphygmomanometer
Timepoint [2] 333428 0
Measured at Baseline, 3 months and 12 months
Secondary outcome [3] 333429 0
LDL cholesterol as measured by fasting blood test
Timepoint [3] 333429 0
Measured at Baseline, 3 months and 12 months
Secondary outcome [4] 333430 0
HDL cholesterol as measured by fasting blood test
Timepoint [4] 333430 0
Measured at Baseline, 3 months and 12 months
Secondary outcome [5] 333441 0
Triglycerides as measured by fasting blood test
Timepoint [5] 333441 0
Measured at Baseline, 3 months and 12 months
Secondary outcome [6] 335176 0
Glucose, as measured by fasting blood test
Timepoint [6] 335176 0
Measured at Baseline, 3 months and 12 months
Secondary outcome [7] 335177 0
Health related quality of life, as measured by the short form 36 (SF-36) of general health related quality of life
Timepoint [7] 335177 0
Measured at Baseline, 3 months and 12 months
Secondary outcome [8] 335460 0
Total fat mass, as measured by dual-energy X-ray absorptiometry (DXA)
Timepoint [8] 335460 0
Measured at Baseline, 3 months and 12 months
Secondary outcome [9] 335461 0
Total fat mass, as measured by bioimpedance spectroscopy
Timepoint [9] 335461 0
Measured at Baseline, 3 months and 12 months
Secondary outcome [10] 335462 0
Total body water, as measured by bioimpedance spectroscopy
Timepoint [10] 335462 0
Measured at Baseline, 3 months and 12 months
Secondary outcome [11] 343933 0
Insulin sensitivity, as measured by minimal modelling of an oral glucose tolerance test
Timepoint [11] 343933 0
Measured at Baseline, 3 months and 12 months
Secondary outcome [12] 343934 0
24 hour blood glucose levels, as measured by 24 hour blood glucose monitoring
Timepoint [12] 343934 0
Measured at Baseline, 3 months and 12 months
Secondary outcome [13] 343935 0
24 hour central blood pressure, as measured by ambulatory 24 hour central blood pressure monitor
Timepoint [13] 343935 0
Measured at Baseline, 3 months and 12 months

Eligibility
Key inclusion criteria
1. Community dwelling adults aged 18-65 years
2. Waist circumference: females >88cm, males >102cm
non-European: famales >80cm, males >90cm
and/or BMI >=27kg/m2
3. Pre-diabetes defined per World Health Organisation as any of the following recent (<3 months) findings:
a) impaired fasting glucose with BGL between 5.5 and 7.0 mmol/L;
b) impaired glucose tolerance with BGL between 7.8 and 11.0 mmol/L after a formal 75g OGTT;
c) HbA1C between 6 and 6.5%
4. Moderate-severe hypoxaemic OSA with AHI>=20/hr and ODI>=10/hr prior to VLED induced weight loss, based on recent (<12 months) polysomography
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Any known contraindications to VLED or exercise
2. Recent weight loss that in the opinion of the treating physician is clinically significant
3. Current or recent (<3months) treatment of OSA
4. Professional drivers who are sleepy
5. Recent (<6 month) history of fall-asleep car crashes or near miss accidents
6. Excessive sleepiness that in the opinion of the treating physician requires immediate CPAP treatment
7. Severe medical (including renal failure) or psychiatric co-morbidity
8. Unstable medical conditions (hypertension, cardiac)
9. Recent use of illicit drugs or alcohol dependence
10. Current (or recent <3 months) use of hypoglycaemic agents
11. Current or previous diagnosis of diabetes mellitus (previous gestational diabetes mellitus not excluded)
12. Respiratory failure including obesity hypoventilation syndrome (OHS) (OHS as diagnosed by physician, based on standard criteria including: BMI >30kg/m2, arterial PaCO2 >45 and evidence of prolonged periods of hypoventilation and hypoxemia during sleep)

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)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Secure randomisation will be achieved through Research Tools software, using a random block size that is not available to staff who enrol participants.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
None
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
30 patients will be required to complete the randomised phase of this pilot study. Allowing for an approximate 20% dropout, n=38 will need to be randomised.

Outcome data will be analysed using Linear Mixed Model Analysis of variance due to expected inter-patient variability and repeated measures. Patients will be random factors. Treatment and time (0 & 3 months) will be fixed factors. The Treatment x Time interaction will be examined to see the specific difference between treatments at just the 3 month time point. Analysis will be by intention to treat and will include all participants who are randomised at 0 months including drop-ins to CPAP and participants who do not adhere to treatment.

Exploratory mixed models analyses of OSA severity accounting for CPAP compliance and weight change will also be conducted using 12 month followup data.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
7/03/2018
Actual
7/03/2018
Date of last participant enrolment
Anticipated
1/07/2020
Actual
12/06/2019
Date of last data collection
Anticipated
1/07/2021
Actual
5/03/2020
Sample size
Target
30
Accrual to date
Final
17
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 7949 0
Woolcock Institute of Medical Research - Glebe
Recruitment hospital [2] 7950 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [3] 7951 0
Liverpool Hospital - Liverpool
Recruitment postcode(s) [1] 15919 0
2037 - Glebe
Recruitment postcode(s) [2] 15920 0
2050 - Camperdown
Recruitment postcode(s) [3] 15921 0
2170 - Liverpool

Funding & Sponsors
Funding source category [1] 295995 0
Charities/Societies/Foundations
Name [1] 295995 0
Diabetes Australia
Country [1] 295995 0
Australia
Funding source category [2] 296095 0
University
Name [2] 296095 0
University of Sydney
Country [2] 296095 0
Australia
Funding source category [3] 301205 0
University
Name [3] 301205 0
Sydney Medical School Foundation, University of Sydney
Country [3] 301205 0
Australia
Primary sponsor type
Other
Name
Woolcock Institute of Medical Research, University of Sydney
Address
PO Box M77 Missendon Rd,
Camperdown 2050
NSW
Country
Australia
Secondary sponsor category [1] 295275 0
None
Name [1] 295275 0
Address [1] 295275 0
Country [1] 295275 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297256 0
Research Ethics and Goverance Office, RPAH
Ethics committee address [1] 297256 0
Ethics committee country [1] 297256 0
Australia
Date submitted for ethics approval [1] 297256 0
13/02/2017
Approval date [1] 297256 0
15/05/2017
Ethics approval number [1] 297256 0
X17-0039

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 3196 3196 0 0
/AnzctrAttachments/372606-X17-0039_FLAT2_Protocol_V5_Aug2018.pdf (Protocol)

Contacts
Principal investigator
Name 73482 0
A/Prof Craig Phillips
Address 73482 0
Woolcock Institute of Medical Research
Mailing address: PO Box M77
Missendon Road
NSW 2050
Physical address: 431 Glebe Point Road
Glebe NSW 2037
Country 73482 0
Australia
Phone 73482 0
+61 2 9114 0000
Fax 73482 0
Email 73482 0
[email protected]
Contact person for public queries
Name 73483 0
Freya Grove
Address 73483 0
Woolcock Institute of Medical Research
Mailing address: PO Box M77
Missendon Road
NSW 2050
Physical address: 431 Glebe Point Road
Glebe NSW 2037
Country 73483 0
Australia
Phone 73483 0
+61 2 9114 0236
Fax 73483 0
Email 73483 0
[email protected]
Contact person for scientific queries
Name 73484 0
Craig Phillips
Address 73484 0
Woolcock Institute of Medical Research
Mailing address: PO Box M77
Missendon Road
NSW 2050
Physical address: 431 Glebe Point Road
Glebe NSW 2037
Country 73484 0
Australia
Phone 73484 0
+61 2 9114 0000
Fax 73484 0
Email 73484 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
individual participant data underlying published results only
When will data be available (start and end dates)?
available after main trial publication, with no end date determined
Available to whom?
only researchers who provide a methodologically sound proposal
Available for what types of analyses?
any purpose
How or where can data be obtained?
requirement to sign data access agreement


What supporting documents are/will be available?

Current supporting documents:

Updated to:
Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.