CPAP Withdrawal and Glucose Metabolism in OSA With Pre-diabetes

Study Overview
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Brief Summary
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The purpose of the current study is to investigate whether temporary, 2-week, CPAP withdrawal will adversely impact glucose metabolism

Detailed Description
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Patients with moderate severe OSA and pre-diabetes who are established and compliant CPAP users will be randomised to withdraw or remain on CPAP for 2 weeks before crossing over to the alternative treatment arm. Glucose metabolism will be monitored using an interstitial (skin based) glucose monitor.

Official Title
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The Impact of 2 Weeks CPAP Withdrawal on Glucose Metabolism in Moderate-Severe Obstructive Sleep Apnoea With Pre-diabetes - A Randomised Controlled Crossover Trial

Conditions
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Obstructive Sleep Apnea, Pre-diabetes

Intervention / Treatment
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* Device: CPAP withdrawal


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Community dwelling adult males and females aged 18-65 years Polysomnography confirmed moderate to severe OSA with apnea hypopnea index (AHI) ≥15/hr within the past 24 months Able to give written informed consent Proficient in English Established CPAP use for at least 1 month with objectively confirmed average use ≥5 hours per night on ≥5 nights per week in the previous 2 weeks. Mean CPAP machine determined AHI<5 events per hour determined over the previous 2 weeks. Diagnosed pre-diabetes defined by the American Diabetes Association as any of the following recent (<3 months) findings: Impaired fasting glucose with a BGL of 5.6 to 6.9 mmol/L Impaired glucose tolerance with a 2-hour BGL of 7.8 to 11.0 mmol/L after a formal 75g Oral Glucose Tolerance Test (OGTT) HbA1C of 5.7% to 6.4% Possession or regular access to a mobile telephone with capability to download and run the Withings Sleep Anlayser App. Exclusion Criteria: Clinically significant co-morbidity (e.g. myocardial infarction, congestive heart failure, stroke, arrythmia, chronic kidney or liver disease, epilepsy, head injury) Severe mental health disorders (e.g. current major depressive disorder, schizophrenia, bipolar disorder) that in the opinion of the investigator is not adequately treated or will significantly affect their participation in the study. Regular (>2 times per month) use of sleep-affecting medication (e.g. benzodiazepines, opioids, antidepressants) Regular night shift work or travel overseas within the last 2 weeks Sleep physician has advised against CPAP withdrawal Pregnancy Active smoking or routine alcohol use (more than 2 standard drinks a day) or excessive caffeine intake (>300 mg a day) or recent (in the past month) use of illicit drugs Current or previous diagnosis of diabetes mellitus (previous gestational diabetes mellitus not excluded) Current or recent (<3 months) use of hypoglycaemic agents Undergoing a weight loss programme Contraindications for use of the FreeStyle Libre Pro Sensor. E.g. Known hypersensitivity to skin adhesives such as those used to attach the sensor to the arm.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CPAP on condition<br>Participants in this arm will begin by using their CPAP as per usual for 2 weeks. Then they will undergo 2 weeks of CPAP withdrawal and stop using their CPAP machine. | Device: CPAP withdrawal<br>* A negative CPAP intervention<br>|
| Experimental: CPAP off condition<br>Participants in this arm will withdraw from their regular CPAP use for 2 weeks. They will then resume their CPAP use for 2 weeks as usual. | Device: CPAP withdrawal<br>* A negative CPAP intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean 24 hour glucose difference between the CPAP on and CPAP off conditions | Average 24 hour glucose difference between CPAP on and CPAP off conditions | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean daytime glucose difference between the CPAP on and CPAP off conditions | Mean Daytime (6:00 AM - 10:00 PM) glucose difference between the CPAP on and CPAP off conditions as measured by the FreeStyle Libre Pro sensor during the 2-week intervention periods. | 2 weeks | 
| Mean night time glucose | Mean Night-time (10:00 PM - 6:00 AM) glucose difference between the CPAP on and CPAP off conditions as measured by the FreeStyle Libre Pro sensor during the 2-week intervention periods. | 2 weeks | 
| Glucose tolerance test | Difference in glucose tolerance as measured by peak 2-hour post 75g glucose load during an Oral Glucose Tolerance Test (OGTT) measured at the end of each 2-week CPAP on and CPAP off conditions. | 2 weeks | 
| Insulin sensitivity | Difference in insulin sensitivity as measured by Minimal Model Assessment (MINMOD) during a 75g glucose load during an OGTT measured at the end of each 2-week CPAP on and CPAP off conditions. | 2 weeks |