Metabolic and Neurobiological changes after Continuous Positive Airway Pressure treatment for Obstructive Sleep Apnea

INTERVENTION: Blinded Continuous Positive Airway Pressure for 12 weeks followed by open‐label CPAP treatment for 12 weeks. The subjects will undergo a 3 night home‐titration using an auto‐titrating machine. The machine will then be set to the 90th percentile on a fixed pressure for the remainder of the study. We are using an identical Sham machine. A trained CPAP technologist who had been involved in other similar sham‐controlled trials is responsible for the allocation of the CPAP machines for this and all other studies. Only this person has access to the sham machines, which she stores separately from the effective CPAP machines. This person will have no direct contact with the subjects. This is a 24 week study. For the first 12 weeks of the study, Week 0 to Week 12, the subject is randomised to use either therapeutic CPAP or sham CPAP every night for the entire 12 weeks. This first 12 weeks is blinded. From Week 12 to Week 24 every subject is changed to receive open‐label therapeutic CPAP every night for the entire 12 weeks. They will return the blinded machine they used from Week 0 to Week 12 and will receive a new therapeutic machine. CONDITION: Obstructive Sleep Apnea PRIMARY OUTCOME: Change in Abdominal Visceral Fat ; Single slice 3D Computerised Tomography (CT) scan of the abdomen. The single slice is taken in relation to a bony landmark (eg T12/L1 or L4/L5 in the axial plane) and hence is reproducible serially. SECONDARY OUTCOME: Change in Anthropometry measurements (weight, height and waist, neck, hip, mid‐arm and mid‐thigh circumferences) Change in Arterial Stiffness and Central Blood Pressure ; ‐ Peripheral and central blood pressure will be assessed by non‐invasive tonometry with a brachial sphymomanometer. This is a measurement of arterial stiffness using pulse wave analysis Change in Blood Hormones Change in Bone Turnover Markers (Osteocalcin, CTX, P1NP, Vitmain D and PTH) and Renal Function (urinary albumin) (blood and urine) Change in Erectile Dysfunction as measured by the modified International Index of Erectile Function (IIEF) and an erectile function survey (EFS). Change in Insulin Sensitivity ; ‐ Insulin sensitivity will be assessed by modified minimal model (MINMOD) analysis of multiple measurements of c‐peptide (at 0, 10, 20, 30, 60, 90 and 120 after a 75g oral glucose load) Change in Physical Activity ; ‐ Physical activity and will be assessed by questionnaire (IPAQ) and objective assessment (Actigraphy). The subject will complete a diary containing questions relating to sleep, such as bed time and time of awakening, while undertaking Actigraphy. Change in Total Body Fat and Muscle Mass ; ‐ Dexa scan and bioimpedence Change in abdominal subcutaneous fat Single slice 3D Computerised Tomography (CT) scan of the abdomen. The single slice is taken in relation to a bony landmark (eg T12/L1 or L4/L5 in the axial plane) and hence is reproducible serially. Change in sleep and breathing parameters ; ‐ Sleep will measured by the gold standard Polysomnograph which requires the attachment of leads to the subject 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. ; INCLUSION CRITERIA: 1. Males aged 18 years or above. 2. Moderate to severe obstructive sleep apnea with respiratory disturbance Index (RDI) =20/hr and inclusive of =3% desaturation (RDI >=20 and ODI >=15) 3. Written informed consent 4. Good general health as defined as men who are community dwelling, with no significant uncontrolled medical problems who are independent in activities of daily living. ; In addition, a functional assessment of the effects of sleepiness will be used. These are validated questionnaires (FOSQ) which assess the impact of sleepiness on multiple activities of daily living (36). The Epworth Sleepiness Scale and assessment of functional outcomes of sleep and neurocognitive function will also be assessed using a 60 minute computer program performed in conjunction with the sleep study. Other measures of sleep at each visit are validated questionnaires and tests (Functional Outcomes of Sleep, Sleepiness scales, driving simulation test). Change in vascular reactivity and repair (as measure by peripheral arterial tonometry (PAT) and endothelial progenitor cell counts) TERTIARY OUTCOME: All the above measured outcomes during the open‐label CPAP period (12‐24 weeks after randomisation) 5. Medical history and physical examination indicating no clinical evidence for significant and uncontrolled cardiovascular (ischemic, hypertension), diabetes, renal, liver, prostate or any other disease.