Diet Exercise and ARmodafinil for treatment resistant sleep apnea (DEAR)

INTERVENTION: This is a factorial trial which means we are testing two types of intervention in the same patients starting at the same time. This means that all patients will be in both the Drug trial and the Lifestyle trial at the same time until the final 3 months of the trial when they will only be on the diet. This is also 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. At baseline patients will see an exercise physiologist and dietitian for approximately 1.5 hours in an individual consultation. They will then participate in individual sessions conducted by the exercise physiologist/dietitian running for 1.5‐2 hours at 2 weeks, 1 month and 4.5 month timepoints. Patients will also recieve a phonecall from exercise physiologist/dietitian at 1.5 months to review their progress. Further approx 1 hour individual consultations at 6, 9 and 12 months to review their progress with the dietitian and exercise physiologist. The Drug Trial is a Superiority Trial (i.e. is the drug better than the placebo?): 3x50mg tablets (ie 150mg) of Armodafinil or placebo once in the morning for 9 months. The Lifestyle Trial is an Equivalence Trial (i.e. are these two diets similarly effective interventions?): Participants will also be randomly allocated for 12 months to either a low GI/high protein diet or a standard low calorie diet as a part of an individualized lifestyle modification program also providing exercise and lifestyle recommendations. CONDITION: Obesity Sleep Apnea PRIMARY OUTCOME: Primary outcome for diet trial: loss of fat mass (grams) as measured by a DXA scan at 12 months. Primary outcome for pharmaceutical trial: Improvement in simulated driving ability quantified by standard deviation in lane position as measured by the AusEd driving simulator in the last 30 minutes of a 90 minute drive. SECONDARY OUTCOME: Diet trial will have 4 secondary outcomes of equal importance: ; B) waist circumference (cm) Diet trial will have 4 secondary outcomes of equal importance: ; C) Sleep apnea severity as measured by the apnea hypopnea index on an overnight polysomnogram Diet trial will have 4 secondary outcomes of equal importance: ; D) Impact of Weight on Quality of Life Questionnaire (IWQOL) Diet trial will have 4 secondary outcomes of equal importance: ; A) weight (kg) Explanatory/efficacy outcome: Energy intake, macronutrient percentage contributions, fat intake, fibre intake, glycaemic load (where measurable). These will be measured by 3 day food and activity diaries preceeding visits and analysed using FoodWorks Software. Explanatory/efficacy outcome: Pharmacogenomics. The Val158Met polymorphism of COMT has been reported to explain the effectiveness of modafinil due to it's effects in the dopaminergic system. We will genotype all patients using high Resolution melt analysis for the val/val met/met or met/val polymorphisms with the hypothesis that val/val subtypes will have superior response to met/met types with met/val types intermediate. Pharmaceutical trial will have 3 secondary outcomes of equal importance: ; B) Sleepiness related quality of life as measured by Epworth Sleepiness Scale (ESS). Pharmaceutical trial will have 3 secondary outcomes of equal importance: ; C) Loss of fat mass (grams) as measured by a DXA scan. Pharmaceutical trial will have 3 secondary outcomes of equal importance: INCLUSION CRITERIA: 1. Males & Females aged 18‐70 years. 2. General or central obesity. BMI:>=27 but less than 40kg/m2 or waist circumference >=80cm for women and >=94cm for men. 3. Moderate‐severe and symptomatic OSA (Apnea Hypopnea Index (AHI) >= 15/hr with concomitant daytime sleepiness ESS>=10 or clinical report of disturbing daytime sleepiness). ; A) Sleepiness related quality of life as measured by the functional outcomes of sleepiness questionnaire (FOSQ) Tertiary outcome: Activity counts via actiwatch and activity questionnaire Tertiary outcome: Bioimpedence analysis to calculate fat mass in the event of patient dropout or data loss of DXA. Tertiary outcome: HOMA index in all participants and HBA1c for those participants who are diabetic at baseline via fasting blood test. Tertiary outcome: Other measurements of driving performance on the AusEd driving simulator including number of crashes, standard deviation in speed variability and secondary reaction time. Tertiary outcome: lipid profile (LDL, HDL, triglycerides) via fasting blood test Tertiary outcome: mean reaction time and number of lapses (<500ms reaction time) on the psychomotor vigilance task Tertiary outcome: Reduction in the Framingham cardiovascular disease risk score Tertiary outcome: Resting blood pressure Tertiary outcome: Working memory measured by the n‐back (2‐back version). The n‐back is a computerised memory task where participants monitor a series of stimuli (in this case letters apearing at different locations on the computer screen) and respond when a stimulus is presented that is the same as the one presented "n" times previously. In this case the participant must press a button on the computer keyboard if the letter that appears on the screen is in the same location as the one 2 times previously. 4. Ambulatory and community‐dwelling. 5. Hold a current drivers license. 6. Must have rejected CPAP and MAS within the past 2 years. Otherwise patients will be encouraged to recommence a standard mechanical treatment.