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Trial registered on ANZCTR


Registration number
ACTRN12619001217190
Ethics application status
Approved
Date submitted
13/08/2019
Date registered
3/09/2019
Date last updated
3/09/2019
Date data sharing statement initially provided
3/09/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
WOLF study: Weight loss with high intensity Functional exercise for men with Obstructive sLeep apnoea.
Scientific title
Body composition effects of high intensity functional exercise training during rapid weight loss in men with obstructive sleep apnoea: A pilot randomised controlled trial
Secondary ID [1] 298475 0
‘Nil known’
Universal Trial Number (UTN)
U1111-1235-1801
Trial acronym
WOLF
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obstructive Sleep Apnoea 313248 0
Obesity 313249 0
Condition category
Condition code
Respiratory 311686 311686 0 0
Sleep apnoea
Metabolic and Endocrine 311687 311687 0 0
Other metabolic disorders
Physical Medicine / Rehabilitation 312507 312507 0 0
Other physical medicine / rehabilitation

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
High intensity functional exercise intervention program for weight loss in overweight and obese patients with obstructive sleep apnoea not treated with continuous positive airway pressure (CPAP).

This is a two arm pilot randomised controlled trial. All participants (n=30) will undergo a commercially available very low energy diet (VLED). Participants will be randomised to either participating in the exercise intervention (n=15) or diet alone (n=15).

The exercise intervention is a 3 month face-to-face stepped program of increasing high intensity functional exercise at a commercially available exercise facility (F45 gyms). Participants will undertake a combination of high intensity (as measured by activity trackers with heart rate monitoring and the Borg RPE scale) resistance and aerobic-based group classes which last a duration of 45 minutes each.

Exercise sessions involve functional motions including but not limited to kicking, punching, rowing, running, pulling, pushing, squatting, lifting, jumping, tossing and twisting. Sessions involve a rotating program of exercises completed at stations. Exercises are performed for approximately 30-45 seconds with a 15 second rest interval between stations.

Classes are conducted by trained exercise professionals employed by the exercise company. The level of training of these exercise professionals range from a tertiary diploma through to a University degree.
The class schedule is as follows:
week 1-2: 2x resistance based classes per week
weeks 3-6: 2x resistance based classes, 1x aerobic based class per week
weeks 7-8: 2x resistance based classes, 2x aerobic based classes per week
weeks 9-12: 2x resistance based classes, 3x aerobic based classes per week

The exercise program will be adapted to meet the specific of each participant and appropriate adjustments will be made. Adherence to the exercise program will be assessed through reports from participants and by the data obtained through activity trackers provided to patients.

The diet component consists of a 3 month period where participants replace meals with a commercially available very low energy diet product for example bars, soups or shakes from brands such as Tony Ferguson, OptiFast, OptiSlim, KickStart or Formulite. Participants will be provided with the VLED product and will be required to prepare each serving according to manufacturer’s instructions. Individual protein requirements and the number of replacements required for each participant will be determined by a trained physician, dietitian or exercise physiologist as per the participant’s adjusted body weight. Protein needs are 1gm/kg of Adjusted Body Weight. Adjusted body weight is calculated using the following:
((Actual Body Weight - Ideal Body Weight) x 0.5) + IBW = Adjusted Body Weight

Actual Body Weight = Current Weight
Ideal Body Weight = Weight at BMI 25

The diet schedule is typically as follows:
weeks 1-8: 3 x meal replacement bars, soups or shakes daily
weeks 9-10: 2 x meal replacement bars, soups or shakes daily and 1 x standard meal
weeks 11-12: 1 x meal replacement bar, soup or shake daily and 2 x standard meals

Participants are encouraged to purchase, prepare and consume an extra 2 cups of vegetables and a teaspoon of oil daily whilst completing the initial 8 weeks of the diet. Patients who reach their desired body weight prior to completion of the 8 week period will be assessed whether to progress to a maintenance meal plan earlier than the 12 week timepoint. 24 hour food recall assessments will determine the rate of compliance of participants.
Intervention code [1] 314725 0
Treatment: Other
Comparator / control treatment
The diet component consists of a 3 month period where participants replace meals with a commercially available very low energy diet product for example bars, soups or shakes from brands such as Tony Ferguson, OptiFast, OptiSlim, KickStart or Formulite. Participants will be provided with the VLED product and will be required to prepare each serving according to manufacturer’s instructions. Individual protein requirements and the number of replacements required for each participant will be determined by a trained physician, dietitian or exercise physiologist as per the participant’s adjusted body weight. Protein needs are 1gm/kg of Adjusted Body Weight. Adjusted body weight is calculated using the following:
((Actual Body Weight - Ideal Body Weight) x 0.5) + IBW = Adjusted Body Weight

Actual Body Weight = Current Weight
Ideal Body Weight = Weight at BMI 25

The diet schedule is typically as follows:
weeks 1-8: 3 x meal replacement bars, soups or shakes daily
weeks 9-10: 2 x meal replacement bars, soups or shakes daily and 1 x standard meal
weeks 11-12: 1 x meal replacement bar, soup or shake daily and 2 x standard meals

Participants are encouraged to purchase, prepare and consume an extra 2 cups of vegetables and a teaspoon of oil daily whilst completing the initial 8 weeks of the diet. Patients who reach their desired body weight prior to completion of the 8 week period will be assessed whether to progress to a maintenance meal plan earlier than the 12 week timepoint. 24 hour food recall assessments will determine the rate of compliance of participants.
Control group
Active

Outcomes
Primary outcome [1] 321167 0
Composite Outcome: Feasibility: recruitment rate – Proportion of people who are seen at the Woolcock Sleep Clinics who are judged to be eligible as defined by the protocol eligibility criteria and clinical judgement of physicians. The proportion people identified as eligible from the Woolcock Sleep Clinics who consent and pass through first stage and second stage phone screening according to protocol eligibility criteria. The proportion people identified as eligible from the Woolcock Sleep Clinics who have passed through phone screening who consent and pass clinical screening according to protocol eligibility criteria. The number of people who pass through Woolcock Sleep Clinics, phone and clinical screening and who consent to randomisation according to protocol eligibility criteria. The amount of time in weeks, months or years from initial recruitment that it takes to reach a total of 30 randomised patients.
Timepoint [1] 321167 0
Time: Before and leading up to randomisation
Primary outcome [2] 321169 0
Composite Outcome: Feasibility (after randomisation): Proportion of patients who complete the 12 week intervention and are compliant with the dietary component (according to binary yes/no self-reported as deemed appropriate in the clinician's opinion).
Participant compliance with exercise intervention as measured by binary yes/no self-reported and documented attendance (corresponding with activity tracker data heart rate summary) as deemed appropriate in the clinician opinion.
In addition, the number of patients who drop out of the study or are not compliant with the prescribed intervention within the 12 week period
Timepoint [2] 321169 0
Time: Compliance is measured at 4, 8 and 12 weeks.
Secondary outcome [1] 374146 0
Outcome: Efficacy: change in patient reported quality of life as measured by the SF-36 survey mental component summary scale.

Timepoint [1] 374146 0
Time: Measured at baseline (study initiation for patients) and 12 weeks post-study commencement.
Secondary outcome [2] 374147 0
Outcome: Efficacy: change in patient reported quality of life as measured by the SF-36 survey physical component summary scale.

Timepoint [2] 374147 0
Time: Measured at baseline (study initiation for patients) and 12 weeks post-study commencement.
Secondary outcome [3] 374148 0
Outcome: Efficacy: change in patient reported somnolence as measured by the self-administered validated functional outcomes of sleep questionnaire (FOSQ) and as a total score.

Timepoint [3] 374148 0
Time: Measured at baseline (study initiation for patients) and 12 weeks post-study commencement.
Secondary outcome [4] 374149 0
Outcome: Efficacy: change in patient reported sleepiness as measured by the Epworth Sleepiness Scale (ESS) survey. This outcome will be measured as a single scale survey with a total score.

Timepoint [4] 374149 0
Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.
Secondary outcome [5] 374150 0
Outcome: Efficacy: Change in patient functional strength as measured by isometric grip strength with a hand dynamometer (kg).
Timepoint [5] 374150 0
Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.
Secondary outcome [6] 374151 0
Outcome: Efficacy: change in body composition as measured by bioimpedance spectroscopy quantification of intracellular and extracellular fluid volume and total body water (L and per cent) and fat and fat free mass (kg and per cent).

Timepoint [6] 374151 0
Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.
Secondary outcome [7] 374152 0
Outcome: Efficacy: change in hip circumference as measured by a standard tape measure (in cm) by a trained physician, dietitian or clinician.
Timepoint [7] 374152 0
Time: Measured at baseline (initial participant consultation), 4 weeks, 8 weeks and 12 weeks post-study commencement.
Secondary outcome [8] 374153 0
Outcome: Efficacy: Efficacy: change in waist circumference as measured by a standard tape measure (in cm) by a trained physician, dietitian or clinician.
Timepoint [8] 374153 0
Time: Measured at baseline (initial participant consultation), 4 weeks, 8 weeks and 12 weeks post-study commencement.
Secondary outcome [9] 374154 0
Outcome: Efficacy: Efficacy: change in neck circumference as measured by a standard tape measure (in cm) by a trained physician, dietitian or clinician.
Timepoint [9] 374154 0
Time: Measured at baseline (initial participant consultation), 4 weeks, 8 weeks and 12 weeks post-study commencement.
Secondary outcome [10] 374164 0
Outcome: Efficacy: change in the standardised body mass index scale as determined by composite measurement of weight using a standardised electronic scale (kg) and height using a standardised stadiometer (cm).

Timepoint [10] 374164 0
Time: Weight measured at baseline (initial participant consultation), 4 weeks, 8 weeks and 12 weeks post-study commencement. Height measured at baseline (initial participant consultation).
Secondary outcome [11] 374165 0
Outcome: Efficacy: change in total adipose mass as measured by dual energy X-ray absorptiometry scan of the whole body.

Timepoint [11] 374165 0
Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.
Secondary outcome [12] 374166 0
Outcome: Efficacy: change in total lean muscle mass as measured by dual energy X-ray absorptiometry scan of the whole body.

Timepoint [12] 374166 0
Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.
Secondary outcome [13] 374167 0
Outcome: Efficacy: change in total bone mass as measured by dual energy X-ray absorptiometry scan of the whole body.

Timepoint [13] 374167 0
Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.
Secondary outcome [14] 374168 0
Outcome: Efficacy: change in bone mineral density as determined by dual energy X-ray absorptiometry scans of the hip and spine (kg/m3).
Timepoint [14] 374168 0
Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.
Secondary outcome [15] 374169 0
Outcome: Efficacy: Change in the severity of obstructive sleep apnoea (OSA) as measured by the apnoea-hypopnea index (AHI) which is the number of apnoeas and hypopneas divided by the total hours of sleep derived from a standard polysomnogram (PSG).

Timepoint [15] 374169 0
Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.
Secondary outcome [16] 374170 0
Outcome: Efficacy: change in resting blood pressure using a standardised and calibrated automatic blood pressure machine.

Timepoint [16] 374170 0
Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.
Secondary outcome [17] 374171 0
Outcome: Efficacy: change in fasting blood glucose (mmol/L) as determined by standard blood testing at a large scale laboratory.

Timepoint [17] 374171 0
Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.
Secondary outcome [18] 374172 0
Outcome: Efficacy: change in fasting insulin (pmol/L) as determined by standard blood testing at a large scale laboratory.

Timepoint [18] 374172 0
Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.
Secondary outcome [19] 374173 0
Outcome: Efficacy: change in high sensitivity C-reactive protein (mg/L) as determined by standard blood testing at a large scale laboratory.

Timepoint [19] 374173 0
Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.
Secondary outcome [20] 374174 0
Outcome: Efficacy: change in total cholesterol, high density lipoprotein and low density lipoprotein (mmol/L) as determined by standard blood testing at a large scale laboratory.
Timepoint [20] 374174 0
Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.
Secondary outcome [21] 374175 0
Outcome: Efficacy: change in triglycerides (mmol/L) as determined by standard blood testing at a large scale laboratory.

Timepoint [21] 374175 0
Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.
Secondary outcome [22] 374176 0
Outcome: Efficacy: change in liver function (U/L) defined as alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate aminotransferase (AST), bilirubin liver enzyme levels as determined by standard blood testing at a large scale laboratory.
Timepoint [22] 374176 0
Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.
Secondary outcome [23] 374177 0
Outcome: Efficacy: change in iron (U/L) as determined by standard blood testing at a large scale laboratory.

Timepoint [23] 374177 0
Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.
Secondary outcome [24] 374178 0
Outcome: Efficacy: change in ferritin (U/L) as determined by standard blood testing at a large scale laboratory.

Timepoint [24] 374178 0
Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.
Secondary outcome [25] 374179 0
Outcome: Safety: change in glomerular filtration rate (U/L) as determined by standard blood testing at a large scale laboratory.

Timepoint [25] 374179 0
Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.
Secondary outcome [26] 374180 0
Outcome: Safety: change in creatinine clearance (U/L) as determined by standard blood testing at a large scale laboratory.

Timepoint [26] 374180 0
Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.
Secondary outcome [27] 374181 0
Outcome: Safety: number of adverse events as defined by GCP as reported by patients to clinicians during clinical consultations.

Timepoint [27] 374181 0
Time: Measured at baseline (study initiation for patients) and 12 weeks post-study commencement.
Secondary outcome [28] 374185 0
Outcome: Safety: number of serious adverse events as defined by the number of unplanned hospitalisations that occur after randomisation and throughout the duration of the trial as reported by participants.

Timepoint [28] 374185 0
Time: Measured at 12 weeks post-study commencement and retrospectively as required when past 12 weeks post study commencement.

Eligibility
Key inclusion criteria
Men aged 18-55 years of age
BMI >27kg/m² or waist circumference >102cm if European, >90cm if non-European
Willing and medically able to participate in a supervised very low energy diet and exercise programme for a 12-week period
Obstructive Sleep Apnoea diagnosed on a PSG with AHI >15 events/hr
Willing and able to complete all assessments outlined in the participant information sheet
Minimum age
18 Years
Maximum age
55 Years
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
Any known contraindications to very low energy diet or exercise
o History of or current presence of eating disorders, significant/extensive food allergies or significant food intolerances (e.g. coeliac disease)
- Unstable Cardiovascular Disease including:
o aortic aneurysm
o Severe left ventricular dysfunction/congestive heart failure
o Severe aortic stenosis
o Unstable ischemic heart disease including angina
o Endocarditis
o Pericarditis (acute)
- Irreversible respiratory disease that causes exercise limitation
- Rapidly progressive or terminal illness
- Severe psychosis or behavioural disturbance or cognitive impairment
- OSA consistently treated with continuous positive airway pressure or mandibular advancement splint
- Severe OSA that in the Physician’s opinion, requires immediate treatment.
- Insulin-Dependent Diabetes Mellitus
- Uncontrolled Type II Diabetes Mellitus

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)
Sequential treatment allocations will be enclosed in numbered, opaque sealed envelopes, and allocated to each participant at the baseline visit.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be enrolled sequentially according to a pre-allocated randomisation list and randomised in concealed variable blocks of 2, 4 and 6 into the VLED or VLED + exercise groups. The randomisation sequence will be pre-determined by a research investigator not involved in testing/training, using a computer-generated random number sequence.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Paired T-tests will be used to test the treatment effect of exercise compared to control. Main effects for the trial will be regarded as statistically significant when p < 0.05. 95% confidence intervals will be used to analyse change in muscle mass in order to measure the variability associated with the response to exercise training compared to the control group. All other secondary outcomes will be statistically tested in the same way.

Recruitment
Recruitment status
Not yet 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)
NSW
Recruitment hospital [1] 13975 0
Woolcock Institute of Medical Research - Glebe
Recruitment postcode(s) [1] 26752 0
2037 - Glebe

Funding & Sponsors
Funding source category [1] 303020 0
Charities/Societies/Foundations
Name [1] 303020 0
The Woolcock Institute of Medical Research
Address [1] 303020 0
Woolcock Institute of Medical Research
431 Glebe Point Road
Glebe NSW 2037 Sydney, Australia
Country [1] 303020 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
The Woolcock Institute of Medical Research
Address
Woolcock Institute of Medical Research
431 Glebe Point Road
Glebe NSW 2037 Sydney, Australia
Country
Australia
Secondary sponsor category [1] 303818 0
None
Name [1] 303818 0
Address [1] 303818 0
Country [1] 303818 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303569 0
Sydney Local Health District Research Committee
Ethics committee address [1] 303569 0
Research Ethics and Governance Office (REGO)
RPAH Medical Centre
Suite 210A, Level 2
100 Carillon Avenue
NEWTOWN NSW 2042
Ethics committee country [1] 303569 0
Australia
Date submitted for ethics approval [1] 303569 0
16/05/2019
Approval date [1] 303569 0
05/07/2019
Ethics approval number [1] 303569 0
2019/ETH11561

Summary
Brief summary
There is consistent evidence showing that very low energy diets (VLEDs) reduce weight amongst patients with obstructive sleep apnoea (OSA) and comorbid obesity. This method of obesity reduction although effective, may be accompanied by an associated change in body composition in patients with OSA, notably concurrent loss of muscle mass. Excessive loss of muscle mass may be undesirable because this tissue is responsible for the majority of resting metabolic rate, regulation of core body temperature, preservation of skeletal integrity, and maintenance of function and quality of life as the body ages.

Our study has a pragmatic design and patients will attend a commercially available high intensity functional exercise training programme. To date, there have been no randomised trials of naturalistic exercise training that is practical and may promote exercise adherence in patients with OSA. We aim to show that this model of training can protect against the loss of muscle mass, as delivered through a programme that can be readily translated to real world settings. Furthermore, we will confirm whether there is an additive benefit of this model of training in addition to a VLED in reducing OSA severity as compared to dietary induced weight loss only.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 94118 0
Dr Elizabeth Cayanan
Address 94118 0
Woolcock Institute of Medical Research
431 Glebe Point Road
Glebe NSW 2037 Sydney, Australia
Country 94118 0
Australia
Phone 94118 0
+61 2 91140411
Fax 94118 0
Email 94118 0
elizabeth.cayanan@sydney.edu.au
Contact person for public queries
Name 94119 0
Dr Elizabeth Cayanan
Address 94119 0
Woolcock Institute of Medical Research
431 Glebe Point Road
Glebe NSW 2037 Sydney, Australia
Country 94119 0
Australia
Phone 94119 0
+61 2 91140411
Fax 94119 0
Email 94119 0
elizabeth.cayanan@sydney.edu.au
Contact person for scientific queries
Name 94120 0
Dr Elizabeth Cayanan
Address 94120 0
Woolcock Institute of Medical Research
431 Glebe Point Road
Glebe NSW 2037 Sydney, Australia
Country 94120 0
Australia
Phone 94120 0
+61 2 9114 0411
Fax 94120 0
Email 94120 0
elizabeth.cayanan@sydney.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Privacy reasons
What supporting documents are/will be available?
Study protocol
Ethical approval
How or where can supporting documents be obtained?
Type [1] 4014 0
Study protocol
Citation [1] 4014 0
Link [1] 4014 0
Email [1] 4014 0
elizabeth.cayanan@sydney.edu.au
Other [1] 4014 0
Attachment [1] 4014 0
Type [2] 4015 0
Ethical approval
Citation [2] 4015 0
Link [2] 4015 0
Email [2] 4015 0
Other [2] 4015 0
Summary results
No Results