ANZCTR - Registration

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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

7/04/2024

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]

‘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

Obesity

Condition category

Condition code

Respiratory

Sleep apnoea

Metabolic and Endocrine

Other metabolic disorders

Physical Medicine / Rehabilitation

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]

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]

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]

Time: Before and leading up to randomisation

Primary outcome [2]

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]

Time: Compliance is measured at 4, 8 and 12 weeks.

Secondary outcome [1]

Outcome: Efficacy: change in patient reported quality of life as measured by the SF-36 survey mental component summary scale.

Timepoint [1]

Time: Measured at baseline (study initiation for patients) and 12 weeks post-study commencement.

Secondary outcome [2]

Outcome: Efficacy: change in patient reported quality of life as measured by the SF-36 survey physical component summary scale.

Timepoint [2]

Time: Measured at baseline (study initiation for patients) and 12 weeks post-study commencement.

Secondary outcome [3]

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]

Time: Measured at baseline (study initiation for patients) and 12 weeks post-study commencement.

Secondary outcome [4]

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]

Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.

Secondary outcome [5]

Outcome: Efficacy: Change in patient functional strength as measured by isometric grip strength with a hand dynamometer (kg).

Timepoint [5]

Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.

Secondary outcome [6]

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]

Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.

Secondary outcome [7]

Outcome: Efficacy: change in hip circumference as measured by a standard tape measure (in cm) by a trained physician, dietitian or clinician.

Timepoint [7]

Time: Measured at baseline (initial participant consultation), 4 weeks, 8 weeks and 12 weeks post-study commencement.

Secondary outcome [8]

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]

Time: Measured at baseline (initial participant consultation), 4 weeks, 8 weeks and 12 weeks post-study commencement.

Secondary outcome [9]

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]

Time: Measured at baseline (initial participant consultation), 4 weeks, 8 weeks and 12 weeks post-study commencement.

Secondary outcome [10]

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]

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]

Outcome: Efficacy: change in total adipose mass as measured by dual energy X-ray absorptiometry scan of the whole body.

Timepoint [11]

Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.

Secondary outcome [12]

Outcome: Efficacy: change in total lean muscle mass as measured by dual energy X-ray absorptiometry scan of the whole body.

Timepoint [12]

Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.

Secondary outcome [13]

Outcome: Efficacy: change in total bone mass as measured by dual energy X-ray absorptiometry scan of the whole body.

Timepoint [13]

Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.

Secondary outcome [14]

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]

Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.

Secondary outcome [15]

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]

Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.

Secondary outcome [16]

Outcome: Efficacy: change in resting blood pressure using a standardised and calibrated automatic blood pressure machine.

Timepoint [16]

Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.

Secondary outcome [17]

Outcome: Efficacy: change in fasting blood glucose (mmol/L) as determined by standard blood testing at a large scale laboratory.

Timepoint [17]

Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.

Secondary outcome [18]

Outcome: Efficacy: change in fasting insulin (pmol/L) as determined by standard blood testing at a large scale laboratory.

Timepoint [18]

Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.

Secondary outcome [19]

Outcome: Efficacy: change in high sensitivity C-reactive protein (mg/L) as determined by standard blood testing at a large scale laboratory.

Timepoint [19]

Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.

Secondary outcome [20]

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]

Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.

Secondary outcome [21]

Outcome: Efficacy: change in triglycerides (mmol/L) as determined by standard blood testing at a large scale laboratory.

Timepoint [21]

Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.

Secondary outcome [22]

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]

Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.

Secondary outcome [23]

Outcome: Efficacy: change in iron (U/L) as determined by standard blood testing at a large scale laboratory.

Timepoint [23]

Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.

Secondary outcome [24]

Outcome: Efficacy: change in ferritin (U/L) as determined by standard blood testing at a large scale laboratory.

Timepoint [24]

Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.

Secondary outcome [25]

Outcome: Safety: change in glomerular filtration rate (U/L) as determined by standard blood testing at a large scale laboratory.

Timepoint [25]

Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.

Secondary outcome [26]

Outcome: Safety: change in creatinine clearance (U/L) as determined by standard blood testing at a large scale laboratory.

Timepoint [26]

Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.

Secondary outcome [27]

Outcome: Safety: number of adverse events as defined by GCP as reported by patients to clinicians during clinical consultations.

Timepoint [27]

Time: Measured at baseline (study initiation for patients) and 12 weeks post-study commencement.

Secondary outcome [28]

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]

Time: Measured at 12 weeks post-study commencement and retrospectively as required when past 12 weeks post study commencement.

Secondary outcome [29]

Efficacy: change in ventilation (l/min) through hypercapnic chemoreflex response to steady-state hypoxia and steady-state hyperoxia, as measured by a purpose-built rebreathing circuit.

Timepoint [29]

Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.

Secondary outcome [30]

Efficacy: change in fasting plasma leptin (ng/ml) as determined by standard blood testing at a large-scale laboratory.

Timepoint [30]

Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.

Secondary outcome [31]

Efficacy: Change in fasting blood glucose (mmol/L) as measured by oral glucose tolerance test.

Timepoint [31]

Time: Measured at baseline (initial participant consultation) and 12 weeks post-study commencement.

Secondary outcome [32]

Efficacy: determination and change in sleep patterns and habits assessed by 1-week modified Karolinska sleep diary. Data supported objectively by concurrent use of GeneActiv acti-watch.

Timepoint [32]

Time: Measured for 1 week. Occurring prior to baseline (initial participant consultation) and 12 weeks post-study commencement.

Secondary outcome [33]

Efficacy: Change in fasting blood insulin (mmol/L) as measured by oral glucose tolerance test.

Timepoint [33]

Time: Measured at baseline (initial participant consultation) and 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

Sex

Males

Can healthy volunteers participate?

Key exclusion criteria

Any known contraindications to very low energy diet or exercise
o History of or current presence of eating disorders
- 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

Completed

Date of first participant enrolment

Anticipated

10/09/2019

Actual

10/09/2019

Date of last participant enrolment

Anticipated

31/03/2023

Actual

4/04/2023

Date of last data collection

Anticipated

30/06/2023

Actual

30/06/2023

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW

Recruitment hospital [1]

Woolcock Institute of Medical Research - Glebe

Recruitment postcode(s) [1]

2037 - Glebe

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

The Woolcock Institute of Medical Research

Address [1]

Woolcock Institute of Medical Research
431 Glebe Point Road
Glebe NSW 2037 Sydney, Australia

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Sydney Local Health District Research Committee

Ethics committee address [1]

Research Ethics and Governance Office (REGO)
RPAH Medical Centre
Suite 210A,  Level 2
100 Carillon Avenue
NEWTOWN NSW 2042

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

16/05/2019

Approval date [1]

05/07/2019

Ethics approval number [1]

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

A general amendment seeking approval for the addition of new investigators, tests, and a site was submitted on 23/6/2021 to the Sydney Local Health District Research Committee. It was approved on 25/6/2021 by the same committee. A subsequent amendment was submitted on 12/5/2022 and approved on 20/5/2022 by the aforementioned committee.

Contacts

Principal investigator

Name

Dr Elizabeth Cayanan

Address

Woolcock Institute of Medical Research
431 Glebe Point Road
Glebe NSW 2037 Sydney, Australia

Country

Australia

Phone

+61 2 91140411

Fax

[email protected]

Contact person for public queries

Name

Elizabeth Cayanan

Address

Woolcock Institute of Medical Research
431 Glebe Point Road
Glebe NSW 2037 Sydney, Australia

Country

Australia

Phone

+61 2 91140411

Fax

[email protected]

Contact person for scientific queries

Name

Elizabeth Cayanan

Address

Woolcock Institute of Medical Research
431 Glebe Point Road
Glebe NSW 2037 Sydney, Australia

Country

Australia

Phone

+61 2 9114 0411

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

Privacy reasons

What supporting documents are/will be available?

Doc. No.	Type	Email	Attachment
4014	Study protocol	[email protected]
4015	Ethical approval		377765-(Uploaded-13-08-2019-10-21-11)-Study-related document.pdf
16274	Ethical approval		377765-(Uploaded-23-07-2021-16-25-41)-Study-related document.pdf
16275	Ethical approval		377765-(Uploaded-31-05-2022-20-02-18)-Study-related document.pdf

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.

Trial Review

Documents added manually

Documents added automatically