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Trial registered on ANZCTR


Registration number
ACTRN12613000191796
Ethics application status
Approved
Date submitted
13/02/2013
Date registered
18/02/2013
Date last updated
14/11/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Sleep, Lifestyle, Energy, Eating, Exercise Program for the management of sleep apnea patients indicated for weight loss treatment: A randomised, controlled pilot study.
Scientific title
Weight loss lifestyle intervention for obese adults with sleep apnea to investigate the effect of treatment on sympathetic activity and cardio-metabolic outcomes.
Secondary ID [1] 281936 0
nil
Universal Trial Number (UTN)
U1111-1139-4487
Trial acronym
SLEEEP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obstructive Sleep Apnoea 288340 0
Obesity 288341 0
Condition category
Condition code
Respiratory 288692 288692 0 0
Sleep apnoea
Diet and Nutrition 288693 288693 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
There are two arms to the trial however all participants will precede random allocation with a 2 month very low energy diet (optifast- consisting of one month of 3 shakes per day followed by 2 weeks of 2 shakes per day + food followed by 2 weeks of 1 shake per day + food. AT two months they will be randomised to one of two diets- a low glycemic index/high protein diet or a standard hypocaloric diet. All patients will receive identical lifestyle modification advice and the same model and volume of self directed exercise will be prescribed for all participants. More information regarding the interventions is outlines below.

This is a parallel study design which means once a patient has been randomly allocated to their intervention groups they will not crossover to the other intervention program.

Very low energy diets are frequently used as an efficient and rapid means of controlled weight loss prior to patients transitioning to a maintenance diet. There is a strong body of evidence using VLED in overweight/obese sleep apnea patients as a precursor to other treatment options. The VLED program structure has been provided by RPAH Metabolism and Obesity Services and has been utilised in clinical services and other research trials frequently in the past. The state of ketosis is achieved as large amounts of fatty acids are broken down in response to extreme energy restriction. VLEDs also contain the recommended daily requirements for vitamins, minerals, trace elements, fatty acids and protein.
Those patients achieving desired body weight prior to completion of the 3 month shake period will be reviewed by the study physician and supervising nutritional staff to determine whether to graduate them to a maintenance diet earlier than projected. The specific VLED program can be found in the standard operating procedures manual. Patients will follow a full VLED program for an 8 week period (3 shakes per day) then an initial transition phase for 2 weeks (2 shakes, one meal) followed by a latter transition phase (1 shake, 2 meals) before initiating their randomised maintenance diet. Shakes will be made up to 240 mL using water, each sachet is 40 g and is equivalent to 635 kJ.

At baseline patients will see an exercise physiologis/nutritionist for approximately 1.5 hours for individual assessment and introduction to the very low energy diet.
Participants will then receive a phone call or skype session at 1 week and 2 weeks to follow up progress with the very low energy diet and allow the opportunity to ask questions. At one month participants will be scheduled to attend the clinic for a routine blood test, safety measures and anthropometry measurements. They will also receive an individual lifestyle modification session focused on exercise. Exercise will be "self managed" throughout the trial however patients will be provided a structured program based on their individual requirements and comorbidities that is focussed on establishing 30 minutes of exercise daily with 2 strength training sessions per week as recommended for the Australian population before progressing to 45-60 minutes of exercise daily (cardio) with 2 strength sessions per week as recommended for clinically significant weight loss. This will be standardised for all participants and a home based strength training program is provided along with clear instructions and demonstrations in clinic. The home based program consists of body weight based exercises such as push ups, participants however will have the option of attending a gym if this is their preference. This is beyond the delivery of the trial however appropriate exercises will be recommended should a participant choose to exercise in this environment.
Once the participant reaches their ideal weight their exercise prescription will revert to the 30 minutes daily cardio exercise plus 2 days strength training as recommended for the adult population for the maintenance of weight and health. This is a lifelong recommendation.

Participants will then attend the clinic at 2 months for an overnight stay where all outcomes are measured. It is at this point that patients are randomised to a low glycemic index/high protein diet or a standard hypocaloric diet. Participants will also receive dietary counselling regarding the transition from a very low calorie diet to their appropriate dietary group.
Calculations will be performed based on the participants current age, height, weight and activity level to determine the calorie intake required to maintain their weight loss. Diet plans have been designed in a unit model whereby filling the units will ensure the various energy requirements/intake is met. Diet plans are equivalent to 5,7,9 and 11 megajoules as required by each individual.

DIETARY GROUP DESCRIPTION: LOW GLYCEMIC INDEX/HIGH PROTEIN DIET
Participants in this group will be coached to adopt a high protein/low GI weight loss diet based on a 500 calorie restriction (as determined by Harris Benedict Equation). The goal of the diet is to maintain a minimum of 5-10 % weight loss over a 12 month period with sustainable changes in eating patterns.
The target macronutrient contribution is 45% of energy from carbohydrates, emphasising low glycaemic sources, 30% from fat and 25% from protein. This macronutrient distribution is similar to the Australian average diet but the GI is lower. The diet will aim to be as low in GI as practical as achieved by replacing higher GI carbohydrates (e.g. conventional white bread, breakfast cereals and potatoes) with lower GI carbohydrates (e.g. Burgen (Registered Trademark) grain breads, oats, pasta, basmati rice). The GI of the low GI/GL diet will be less than 50 (glucose is equivalent to 100) and calculated using published data for Australian foods. The diet will emphasise lean sources of protein and restriction of saturated and transfats (but not total fat).
Participants will be provided with The Shoppers Guide to Low GI that outline the carbohydrate choices and the food amounts that constitute one serving. They will also be provided information on the whole diet to ensure energy and overall nutrient balance.

Both diets incorporate all food groups (including cereals, grains, pastas, breads, dairy products, meats and other proteins, fish and seafood, fruit, vegetables and healthy fats and occasional foods. They are healthy sustainable diets. The dietary intervention will finish at 6 months however patients are encouraged to maintain their weight loss by permanently following their dietary pattern. Each diet promotes a lifelong way of healthy eating that is indicated for health benefits unless development of a specific medical condition later in life (such as liver disease or kidney failure- not related to these diets) warrants future dietetics assessment and recommendations

The lifestyle modification sessions continue with a 3 month phone or skype session, a 4.5 month phonecall or skype session and a 6 month overnight stay where all outcomes are measured.
The lifestyle modification sessions entail dietary and exercise advice as described as well as health coaching and the use of appropriate tools to aid behaviour change. This incorporates action planning, the recognition and management of lapses and relapses and long term goal setting.

Patients presenting with low adherence to dietary program or demonstrating a need for additional support via more frequent anthropometry may be offered to participate in face to face sessions instead of skype/phonecall sessions. This will be at the discretion of the study physicians and study coordinator where a consensus must be met based on weight loss and patient compliance monitoring.

At 6 months the active intervention ceases and patients are encouraged to maintain their weight and health for the following 6 months where they will receive a follow up phonecall at 9 months and a final overnight stay at 12 months to assess all outcomes.
Intervention code [1] 286498 0
Lifestyle
Comparator / control treatment
In this second arm of the trial all participants will precede randomisation with a 2 month very low energy diet (optifast- consisting of one month of 3 shakes per day followed by 2 weeks of 2 shakes per day + food followed by 2 weeks of 1 shake per day + food. AT two months participants will be randomised and the second arm is a standard hypocaloric diet. All patients will receive identical lifestyle modification advice and the same model and volume of self directed exercise will be prescribed for all participants. More information regarding the interventions is outlines below.

This is a parallel study design which means once a patient has been randomly allocated to their intervention groups they will not crossover to the other intervention program.

Very low energy diets are frequently used as an efficient and rapid means of controlled weight loss prior to patients transitioning to a maintenance diet. There is a strong body of evidence using VLED in overweight/obese sleep apnea patients as a precursor to other treatment options. The VLED program structure has been provided by RPAH Metabolism and Obesity Services and has been utilised in clinical services and other research trials frequently in the past. The state of ketosis is achieved as large amounts of fatty acids are broken down in response to extreme energy restriction. VLEDs also contain the recommended daily requirements for vitamins, minerals, trace elements, fatty acids and protein.
Those patients achieving desired body weight prior to completion of the 3 month shake period will be reviewed by the study physician and supervising nutritional staff to determine whether to graduate them to a maintenance diet earlier than projected. The specific VLED program can be found in the standard operating procedures manual. Patients will follow a full VLED program for an 8 week period (3 shakes per day) then an initial transition phase for 2 weeks (2 shakes, one meal) followed by a latter transition phase (1 shake, 2 meals) before initiating their randomised maintenance diet. Shakes will be made up to 240 mL using water, each sachet is 40 g and is equivalent to 635 kJ.


At baseline patients will see an exercise physiologis/nutritionist for approximately 1.5 hours for individual assessment and introduction to the very low energy diet.
Participants will then receive a phone call or skype session at 1 week and 2 weeks to follow up progress with the very low energy diet and allow the opportunity to ask questions. At one month participants will be scheduled to attend the clinic for a routine blood test, safety measures and anthropometry measurements. They will also receive an individual lifestyle modification session focused on exercise. Exercise will be "self managed" throughout the trial however patients will be provided a structured program based on their individual requirements and comorbidities that is focussed on establishing 30 minutes of exercise daily with 2 strength training sessions per week as recommended for the Australian population before progressing to 45-60 minutes of exercise daily (cardio) with 2 strength sessions per week as recommended for clinically significant weight loss. This will be standardised for all participants and a home based strength training program is provided along with clear instructions and demonstrations in clinic. The home based program consists of body weight based exercises such as push ups, participants however will have the option of attending a gym if this is their preference. This is beyond the delivery of the trial however appropriate exercises will be recommended should a participant choose to exercise in this environment.
Once the participant reaches their ideal weight their exercise prescription will revert to the 30 minutes daily cardio exercise plus 2 days strength training as recommended for the adult population for the maintenance of weight and health. This is a lifelong recommendation.

Participants will then attend the clinic at 2 months for an overnight stay where all outcomes are measured. It is at this point that patients are randomised to a low glycemic index/high protein diet or a standard hypocaloric diet. Participants will also receive dietary counselling regarding the transition from a very low calorie diet to their appropriate dietary group.
Calculations will be performed based on the participants current age, height, weight and activity level to determine the calorie intake required to maintain their weight loss. Diet plans have been designed in a unit model whereby filling the units will ensure the various energy requirements/intake is met. Diet plans are equivalent to 5,7,9 and 11 megajoules as required by each individual.

DIETARY GROUP DESCRIPTION: STANDARD HYPOCALORIC DIET
Participants in this group will be coached to adopt a variety of healthy foods from all food groups based on a 500 calorie restriction (as determined by Harris Benedict Equation). It will be modelled around the current Australian guide to healthy eating. The goal of the diet is to maintain a minimum of 5-10 % weight loss over a 12 month period with sustainable changes in eating patterns. Patients will be encouraged to choose whole grains, sources of high fibre, reduce sugar intake and decrease fat intake (specifically saturated and trans fats). The target macronutrient contribution is 60% of energy from carbohydrates, 23% from fat and 17% from protein. This macronutrient distribution is within the recommendation ranges provided by the Australian Guide to Healthy Eating.
Participants will be provided with The Australian Guide to Healthy Eating that outlines the carbohydrate choices and the food amounts that constitute one serving. They will also be provided information on the whole diet to ensure energy and overall nutrient balance.

The standard hypocaloric diet group receive a copy of the Australian guide to healthy eating and are educated regarding portions sizes. They are encouraged to increase fibre intake and reduce saturated fat intake and consume a variety of nutritious foods.

Both diets incorporate all food groups (including cereals, grains, pastas, breads, dairy products, meats and other proteins, fish and seafood, fruit, vegetables and healthy fats and occasional foods. They are healthy sustainable diets. The dietary intervention will finish at 6 months however patients are encouraged to maintain their weight loss by permanently following their dietary pattern. Each diet promotes a lifelong way of healthy eating that is indicated for health benefits unless development of a specific medical condition later in life (such as liver disease or kidney failure- not related to these diets) warrants future dietetics assessment and recommendations

The lifestyle modification sessions continue with a 3 month phone or skype session, a 4.5 month phonecall or skype session and a 6 month overnight stay where all outcomes are measured.
The lifestyle modification sessions entail dietary and exercise advice as described as well as health coaching and the use of appropriate tools to aid behaviour change. This incorporates action planning, the recognition and management of lapses and relapses and long term goal setting.

Patients presenting with low adherence to dietary program or demonstrating a need for additional support via more frequent anthropometry may be offered to participate in face to face sessions instead of skype/phonecall sessions. This will be at the discretion of the study physicians and study coordinator where a consensus must be met based on weight loss and patient compliance monitoring.

At 6 months the active intervention ceases and patients are encouraged to maintain their weight and health for the following 6 months where they will receive a follow up phonecall at 9 months and a final overnight stay at 12 months to assess all outcomes.
Control group
Active

Outcomes
Primary outcome [1] 300173 0
Change in waist circumference (measured in cm)
This outcome was ethically approved on 1/3/16.
Timepoint [1] 300173 0
Change between 2 and 12 months
Secondary outcome [1] 301111 0
Sympathetic Activity (Effect Modifiers)
24 hour urinary catecholamines: Collected over a 24 hour period and split into wake versus sleep period to measure sympathetic activity (specifically dopamine, norepinephrine, epinephrine and serotonin)
Timepoint [1] 301111 0
Baseline, 2 months, 6 months, 12 months
Secondary outcome [2] 301112 0
Sympathetic Activity (Effect Modifiers)

24 hour cardiopulmonary coupling: to assess sleep quality via a sleep spectrogram (a visualisation or image created by CPC analysis that displays the integrated or coupled) biological oscillations of sleep.
Timepoint [2] 301112 0
Baseline, 2 months, 6 months, 12 months
Secondary outcome [3] 301113 0
Body composition measured through bioelectrical impedance analysis
Timepoint [3] 301113 0
Baseline, 1 month, 2 months, 6 months, 12 months
Secondary outcome [4] 301114 0
Sympathetic activity assessed with 24 hour urinary catecholamines
Timepoint [4] 301114 0
Baseline, 2 months, 6 months, 12 months
Secondary outcome [5] 301115 0
Apnea-Hypopnea Index (AHI): measured via polysomnography to define sleep apnea severity. Leads will be attached to the subject’s head 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
Timepoint [5] 301115 0
baseline, 2 months and 12 months.
Secondary outcome [6] 301116 0
Waist Circumference: measured using the International Diabetes Federation Guidelines. The unit will be cm loss
Timepoint [6] 301116 0
baseline, 1 month, 2 months, 6 months and 12 months.
Secondary outcome [7] 301117 0
The SF-36 questionnaire: as a tool to measure general health related quality of life in the domains of physical and mental health
Timepoint [7] 301117 0
baseline, 2 months, 6 months and 12 months
Secondary outcome [8] 301118 0
Sympathetic Activity (Effect Modifiers)

24 hour heart rate variability: heart rate is modulated by the combined effects of the sympathetic and parasympathetic nervous systems. Measurement of heart rate changes over time (i.e. heart rate variability) provide information about autonomic functioning) and can be measured as a domain of cardiopulmonary coupling. Heart rate variability (HRV) is the standard deviation of the R-R interval and we expect will increase with weight loss.
Timepoint [8] 301118 0
baseline, 2 months, 6 months and 12 months
Secondary outcome [9] 301119 0
Sympathetic Activity (Effect Modifiers)

Core temperature, skin temperature and sweating: Measured using ibutton, electrodermal activity (through skin) and via a component of the CPC Embla device. Objective assessment via electro- dermal activity (EDA). Electrodermal activity will be measured with NoiseFree single bio-potential silver-silver / chloride electrodes connected to the Em- blaTM digital recording device. A thermoregulatory index will also be calculated based upon the autonomic function questionnaire.
Timepoint [9] 301119 0
Baseline, 2 months, 6 months and 12 months
Secondary outcome [10] 301120 0
Clinical Symptoms Associated with Sleep Apnea and Phenotyping of Sleep Apnea

Anthropometric measurements: including height (only measured at baseline); change in weight (kg) , neck circumference (cm) and hip circumference (cm).
Timepoint [10] 301120 0
baseline, 1 month, 2 months, 6 months and 12 months.
Secondary outcome [11] 301121 0
Clinical Symptoms Associated with Sleep Apnea and Phenotyping of Sleep Apnea

Change in grams of fat mass, fat free mass, total body water, intracellular fluid and extracellular fluid measured by biolelectical impedance analysis
Timepoint [11] 301121 0
baseline and 2 months, baseline and 6 months.
Secondary outcome [12] 301122 0
Clinical Symptoms Associated with Sleep Apnea and Phenotyping of Sleep Apnea

Polysomnography: Sleep shall be monitored using standard polysomnography at the Woolcock Institute for the purpose of determining sleep apnea severity via RDI, sleep quality and sleep efficiency. Leads will be attached to the subject’s head 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
Timepoint [12] 301122 0
Baseline, 2 months and 12 months.
Secondary outcome [13] 301139 0
Clinical Symptoms Associated with Sleep Apnea and Phenotyping of Sleep Apnea

Laboratory Analyses for metabolic risk, inflammatory markers and hormones: lipoprotein profile, plasma leptin, insulin sensitivity (HOMA), triacylglycerol concentrations, C-reactive protein, inflammatory markers (IL-4, IL-6, TNF-a), liver function tests, cortisol, ghrelin, adiponectin, testosterone, luteinising hormone and a genetic marker for the COMT polymorphism. Standard venepuncturewill be used to measure the hormonal and cardiovascular markers noted. Serum will be frozen and processed by a central laboratory. If the patient consents, blood will also be taken and stored for genetic testing at a future occasion.
o Lipids electrolytes and liver function 1 X 7ml (gold top gel tube)
o Full blood count takes 1 X 4ml EDTA (purple top tube)
o Hormones and fasting insulin/glucose 1 x 7 mL (gold top)
o At the baseline visit a 4ml sample will be taken for genetic testing for the COMT polymorphisms that have been reported to predict sleepiness.
Timepoint [13] 301139 0
A 20ml blood sample will be collected at baseline, 1 month, 2 month, 6 month and 12 month visits (genetic polymorphisms will be collected/measured at baseline visit only as this outcome will not change)
Secondary outcome [14] 301140 0
Clinical Symptoms Associated with Sleep Apnea and Phenotyping of Sleep Apnea

Vitals (resting blood pressure and heart rate): Blood pressure (BP), and heart rate (HR). The BP and HR are measured using a consistent device and cuff throughout the study on the same arm used at baseline that showed the higher value. At least 2 measurements should be taken (with 1-2 minutes between) after at least 5 minutes of sitting and resting. A third measure should be taken if there is >10 mmHg discrepancy between the first two measurements.
Timepoint [14] 301140 0
Baseline, 1 month, 2 months, 6 months, 12 months
Secondary outcome [15] 301153 0
Clinical Symptoms Associated with Sleep Apnea and Phenotyping of Sleep Apnea

Sleepiness related quality of life: as measured by the functional outcomes of sleepiness questionnaire (FOSQ) and Epworth Sleepiness Scale (ESS)
Timepoint [15] 301153 0
Baseline, 2 month, 6 month and 12 month
Secondary outcome [16] 301154 0
Clinical Symptoms Associated with Sleep Apnea and Phenotyping of Sleep Apnea

Craniofacial Photography: a photograph of the participants face will be taken with appropriate markers attached to determine craniofacial dimensions specific to sleep apnea.
Timepoint [16] 301154 0
baseline, 2 month, 6 month, 12 month
Secondary outcome [17] 301155 0
Self Efficacy

Self Regulation Questionnaire (SRQ): measures the ability to develop, implement, and flexibly maintain planned behaviour in order to achieve one's goals.
Timepoint [17] 301155 0
Baseline, 2 months, 6 months and 12 months
Secondary outcome [18] 301156 0
Self Efficacy

General Self Efficacy Scale: to assess a general sense of perceived self efficacy
Timepoint [18] 301156 0
baseline, 2 months, 6 months, 12 months
Secondary outcome [19] 301157 0
Self Efficacy

Bandura’s nutrition and physical exercise self efficacy scale
Timepoint [19] 301157 0
Baseline, 2 months, 6 months and 12 months
Secondary outcome [20] 301158 0
Self Efficacy

The Kentucky Inventory of Mindfulness Skills (KIMS; Baer 2004) will be used to assess the specific mindfulness skills of participants
Timepoint [20] 301158 0
baseline, 2 months, 6 months, 12 months
Secondary outcome [21] 301159 0
Quality of Life Measures

Depression and Anxiety and Stress Scale (DASS): to measure the three related negative emotional states of depression, anxiety and tension/stress.
Timepoint [21] 301159 0
baseline, 2 months, 6 months, 12 months
Secondary outcome [22] 301160 0
Quality of Life Measures

Impact of Weight on Quality of Life Questionnaire: to assess the effects of the obese condition on the quality of life of persons seeking treatment for this condition.
Timepoint [22] 301160 0
baseline, 2 months, 6 months, 12 months
Secondary outcome [23] 301161 0
Quality of Life Measures

Three Factor Eating Questionnaire: (TFEQ; Stunkard & Messick, 1985) will be used as a measure of eating behaviour, specifically assessing cognitive restraint, disinhibition of eating, and perceived hunger.
Timepoint [23] 301161 0
baseline, 2 months, 6 months, 12 months
Secondary outcome [24] 301167 0
Qualitative/Habitual Outcomes

Food and Activity Diary: Minimum 4 day collection period (3 weekdays and 2 weekend days) to assess habitual dietary intake and energy expenditure via the Bouchard Questionnaire.
Timepoint [24] 301167 0
baseline, 2 months, 6 months, 12 months
Secondary outcome [25] 301169 0
Qualitative/Habitual Outcomes

Habitual physical activity, energy expenditure, sleep and sedentary behaviour: Actigraph accelerometers will be worn during all waking hours for seven days on the non dominant wrist at all times to monitor activity. These wrist activity monitors will be used to estimate sleep and wake periods by using activity measured by wrist accelerometry. We will also be using this device’s raw activity counts as an objective measure of physical activity levels. Sensewear armbands will also be worn for a seven day period on the upper portion of the non-dominant arm to quantify energy expenditure, sleep, body temperature, intensity of physical activity and steps taken.
Timepoint [25] 301169 0
baseline, 2 months, 6 months, 12 months
Secondary outcome [26] 301170 0
Qualitative/Habitual Outcomes

Food Habits Questionnaire (FHQ95): To assess usual eating habits
Timepoint [26] 301170 0
baseline, 2 months, 6 months, 12 months
Secondary outcome [27] 301171 0
Qualitative/Habitual Outcomes

International Physical Activity Questionnaire (IPAQ): To provide health related physical activity data
Timepoint [27] 301171 0
baseline, 2 months, 6 months, 12 months
Secondary outcome [28] 301172 0
Screening Questionnaire

Eating Disorder Examination Questionnaire: (EDE-Q; Fairburn & Cooper, 1993) will be used to assess the specific psychopathology of eating disorders. The EDE-Q is comprised of four subscales: restraint, weight, shape and eating concerns.
Timepoint [28] 301172 0
Baseline only- inclusion criteria

Eligibility
Key inclusion criteria
The following inclusion criteria enable the volunteer to participate in the SLEEEP Study:
Males & Females aged 18-65 years.

General or central obesity: BMI: greater than or equal to 30kg/m2 (greater than or equal to 26kg/m2 amongst non-Europeans) or waist circumference greater than or equal to 88cm for women and greater than or equal to 102cm for men (greater than or equal to 90cm in men and greater than or equal to 80cm in women who are non-European).

Willing and medically able to participate in a supervised very low energy diet (Optifast) and the dietary and lifestyle modification groups for a 12 month period.

Mild-severe, symptomatic OSA (degree of symptoms at the treating physician’s discretion based on overnight sleep study report)

No history of or current presence of eating disorders , significant/extensive food allergies or significant food intolerances (e.g. coeliac disease)

Willing and able to complete all assessments outlined in participant information sheet

Hold a current driver’s license or have access to transport.
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Unstable aortic aneurysm
Rapidly progressive or terminal illness
Severe left ventricular dysfunction/end stage congestive heart failure
Severe aortic stenosis
Severe psychosis or behavioural disturbance or cognitive impairment
Patients known to be involved in illegal activity

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)
The randomisation sequence will be pre-determined by a research assistant not involved in testing/training, using a computer-generated random number sequence. Sequential treatment allocations will be enclosed in numbered, opaque sealed envelopes, and distributed to each participant at their baseline visit stratified according to treatment to evenly distribute patients between treatment groups and aid generalisability.

Recruitment will primarily be conducted through the physicians at the Sleep Clinics of:
The Woolcock Institute
Royal Prince Alfred Hospital
Potentially eligible participants will be given an information sheet detailing the aims of the study, basic eligibility criteria and the study staff coordinator contact number to call if they are interested in participating. Participants who are recruited from one of the Sleep Clinics listed may fill in a form requesting to be contacted by a study investigator if they prefer. Other sources of potential volunteers include:

The Woolcock Clinic: Treating physicians, all Woolcock affiliated, will be alerted to the study and asked to inform candidate patients of the trial. Patients will be assured that an unwillingness to participate in the trial will in no way affect their ongoing treatment and level of care.

Local print media including newspaper advertisements, local newsletters, university mail and newsletters etc.

Specialist/GP Referral and potential advertisements in GP wait rooms

Sleep Disorders Australia website

Australasian Sleep Trials Network website

Australasian Sleep Association website

Databases from previous studies where individuals have consented to be contacted for future studies

Advertisements may also be displayed in health magazines, websites or papers that are targeted at similar patients. Sleep Disorders Australia and larger general practices will also be advised of the trial to advertise the trial for potential participants.
To assess the eligibility for the SLEEEP Study, interested volunteers will undergo a telephone screening. The questions on the form were designed to address all inclusion and exclusion criteria. A 15-30 minute phone call from the interviewer will allow all volunteers to answer the questions and ask any that they may have about the study. A confidential study database will maintain a record of all screens conducted and indicate potential participants and note those who wish not to be contacted in the future.
Participants will be informed about their eligibility or be placed on hold for further medical information and/or investigation(s). An information package will be sent via email or post to the potentially eligible subjects and will include an appointment to see the study physician, information regarding the location of the screening, testing venue, a permission slip for access of medical records, a study information sheet including a brief outline of the assessment procedures and a brochure outlining the weight loss program and diets. If not eligible, the researcher will ask volunteer’s permission to retain their contact details in case their situation changes over time and they become eligible at a later date. To obtain medical clarification for volunteers, letters will be sent to their relative doctors along with the signed permission slip from the volunteers indicating that the physician may release relevant medical information where this information may be lacking at the discretion of the study physician.
Potentially eligible participants will be given the informed consent and will be guided through all aspects of the information sheet and offered the opportunity to ask any questions related to the study when they attend their screening visit at the Woolcock Institute. Those subjects who agree to participate in the area will be asked to sign the consent form according to the guidelines of the Sydney Local Health District’s Ethics Review Committee. If the patient is willing to participate in the study, they will be requested to also provide written and witnessed informed consent for use of a sample for Pharmacogenetic Research. To determine final eligibility the study physician will examine, consult and review the medical records and telephone screening of each subject. Screening bloods will be collected to check against inclusion/exclusion criteria along with a 12 lead resting ECG. If necessary, a screening overnight PSG will requested to confirm OSA prior to the participant being entered into the study.
Eligible subjects will then be asked to attend a baseline visit. Baseline visits will take place overnight at The Woolcock Institute (Glebe). Eligible volunteers will all commence Optifast for the proceeding two month period prior to be randomised to one of the intervention arms as stratified by treatment versus non-treatment use.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Only eligible adults providing written informed consent according to the current approved protocol will be enrolled into the trial. OSA volunteers will be enrolled sequentially according to two pre- allocated randomisation lists stratified as the treatment and non-treatment users and randomised in concealed variable blocks of 4-8 into the standard low calorie diet and lifestyle modification program OR a low GI and High protein diet and lifestyle modification program following three months of VLED. The dietary intervention is an open label study as participants cannot be blinded to their treatment allocation.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Randomisation will not occur until the completion of a 2 month very low energy diet where patients are able to achieve 5-10% weight loss.

Patients who are unable to tolerate the VLED will be considered by the medical supervisory staff to determine whether they are able to reduce their VLED prescription while maintaining an acceptable rate of weight loss so as to enable them to remain in the study. These decisions will be considered on a case by case basis. Patients who are unable to be randomised due to inability to lose weight through the VLED will undertake an exit interview prior to exiting the trial and will be offered medical support as required.


BOOSTER SESSIONS
Patients presenting with low adherence to dietary program or demonstrating a need for additional support via more frequent anthropometry may be offered to participate in face to face sessions instead of skype/phonecall sessions. This will be at the discretion of the study physicians and study coordinator where a consensus must be met based on weight loss and patient compliance monitoring.
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
This is a pilot trial to describe the variability of weight regain in these two different maintenance diets following a very low energy diet. Recruitment will enrol a maximum number of participants within a target period of six months. No power calculations have been conducted as this is a pilot trial however we anticipate that 20 people will be recruited for each study arm for a total of n=40 over the 6 month recruitment phase. Data will be analysed on an intention-to-treat basis. Mixed model analyses of variance will be used to test each diet treatment effect. Treatment will be the fixed effect and individual patients the random effect. Main effects for the trial will be regarded as statistically significant when p < 0.05. 95% confidence intervals will be used to analyse weight rebound in order to measure the variability associated with weight regain.

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)
NSW
Recruitment hospital [1] 574 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 6316 0
2037 - Glebe
Recruitment postcode(s) [2] 6317 0
2000 - Sydney
Recruitment postcode(s) [3] 6318 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 286727 0
Government body
Name [1] 286727 0
NHMRC Centre for Integrated Research and Understanding of Sleep
Address [1] 286727 0
Woolcock Institute of Medical Research
University of Sydney NSW 2006
Country [1] 286727 0
Australia
Primary sponsor type
Other
Name
The Woolcock Institute
Address
Woolcock Institute of Medical Research
431 Glebe Point Road
Glebe. 2037
Country
Australia
Secondary sponsor category [1] 285502 0
Hospital
Name [1] 285502 0
Sydney Local Area Health District- Ethics Review Committee (RPAH Zone)
Address [1] 285502 0
PO Box M30
Missendon Road, NSW
2050
Country [1] 285502 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288799 0
Sydney Local Health District- Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 288799 0
Research Development Office
Royal Prince Alfred Hospital
CAMPERDOWN NSW 2050
Ethics committee country [1] 288799 0
Australia
Date submitted for ethics approval [1] 288799 0
12/12/2012
Approval date [1] 288799 0
13/12/2012
Ethics approval number [1] 288799 0
HREC/12/RPAH/533

Summary
Brief summary
This trial will investigate the effect of two different diets for patients with obstructive sleep apnea who are trying to lose weight. This study will look at changes in sympathetic activity (which controls your fight or flight response) as well as assessing your cardiometabolic health and disease risk factors. All participants who choose to enrol in the study will follow a very low energy diet for three months followed by nine months of free health coaching and weight loss therapy delivered by an accredited exercise physiologist and nutritionist. Those who proceed with the trial will be randomised to a low glycemic index/high protein diet or a standard low calorie diet based on the Australian guide to healthy eating after following a very low energy diet for three months.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 1227 1227 0 0

Contacts
Principal investigator
Name 37778 0
Prof Ron Grunstein
Address 37778 0
The Woolcock Institute
431 Glebe Point Road
Glebe. NSW
2037
Country 37778 0
Australia
Phone 37778 0
61 2 9114 0007
Fax 37778 0
61 2 9114 0014
Email 37778 0
ron.grunstein@sydney.edu.au
Contact person for public queries
Name 37779 0
Miss Elizabeth Machan
Address 37779 0
The Woolcock Institute
431 Glebe Point Road
Glebe. NSW
2037
Country 37779 0
Australia
Phone 37779 0
61 2 9114 0456
Fax 37779 0
61 2 9114 0014
Email 37779 0
elizabeth.machan@sydney.edu.au
Contact person for scientific queries
Name 37780 0
Miss Elizabeth Machan
Address 37780 0
The Woolcock Institute
431 Glebe Point Road
Glebe. NSW
2037
Country 37780 0
Australia
Phone 37780 0
61 2 9114 0456
Fax 37780 0
61 2 9114 0014
Email 37780 0
elizabeth.machan@sydney.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