Sleep, Lifestyle, Energy, Eating, Exercise Program for the management of sleep apnea patients indicated for weight loss treatment: A randomised, controlled pilot study.

INTERVENTION: 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. 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 Har CONDITION: Obesity Obstructive Sleep Apnoea PRIMARY OUTCOME: Change in waist circumference (measured in cm) ; This outcome was ethically approved on 1/3/16. 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. SECONDARY OUTCOME: 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 Body composition measured through bioelectrical impedance analysis 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). ; 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 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. 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) ; ; ; INCLUSION CRITERIA: The following inclusion criteria enable the volunteer to participate in the SLEEEP Study: Males & Females aged 18‐65 years. 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. ; 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. 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 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) 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. Qualitative/Habitual Outcomes ; ; Food Habits Questionnaire (FHQ95): To assess usual eating habits 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. 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. Qualitative/Habitual Outcomes ; ; International Physical Activity Questionnaire (IPAQ): To provide health related physical activity data 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. 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. 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. Screening Questionnaire ; ; ; Bandura’s nutrition and physical exercise self efficacy scale Self Efficacy ; ; General Self Efficacy Scale: to assess a general sense of perceived self efficacy Self Efficacy ; ; Self Regulation Questionnaire (SRQ): measures the ability to develop, implement, and flexibly maintain planned behaviour in order to achieve one's goals. Self Efficacy ; ; The Kentucky Inventory of Mindfulness Skills (KIMS; Baer 2004) will be used to assess the specific mindfulness skills of participants Sympathetic Activity (Effect Modifiers) ; 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. Self Efficacy ; 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. 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. 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. 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) Sympathetic activity assessed with 24 hour urinary catecholamines The SF‐36 questionnaire: as a tool to measure general health related quality of life in the domains of physical and mental health Waist Circumference: measured using the International Diabetes Federation Guidelines. The unit will be cm loss 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). 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 al