CPAP and Glucose Metabolism in Non-Diabetic OSA Subjects

The Impact of CPAP on Glucose Metabolism in Moderate-Severe Obstructive Sleep Apnoea Patients Without Diabetes - an Observational Study

The purpose of the current study is to investigate whether alleviation of OSA by CPAP positively impacts glucose metabolism in non-diabetic patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Obstructive Sleep Apnea; Pre-diabetes
• Intervention / Treatment: Device: CPAP

Detailed Description

Glucose metabolism in patients newly diagnosed with moderate-severe OSA and without diabetes will be monitored for two weeks prior to commencement of CPAP using a CGM. They will consume a 75g oral glucose drink fasted on waking twice during the two-week monitoring period, having consumed a standardised meal the evening prior. After establishing CPAP use for at least four weeks they will undergo the same protocol as for the observation period prior to commencing CPAP. Glucose metabolism will be monitored using an interstitial (skin based) glucose monitor.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: David J Sherring, MBBS, DClinD; Phone Number: 0407886698; Email: dshe7670@uni.sydney.edu.au

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
      • Contact: Estelle Ali; Phone Number: +61 468805641; Email: estelle.ali@health.nsw.gov.au
      • Contact: Professor Brendon Yee
    • Macquarie Park, New South Wales, Australia, 2113
      • Woolcock Institute of Medical Research
      • Contact: Grigori Kaplan, PhD; Phone Number: +61 9114 0412; Email: grigori.kaplan@sydney.edu.au
      • Contact: Craig Phillips, PhD
      • Contact: Brendon Yee, PhD FRACP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Community dwelling adult males and females aged 18-65 years
2. Polysomnography confirmed moderate to severe OSA with apnea hypopnea index (AHI) ≥15/hr within the past 60 months
3. Able to give written informed consent
4. Proficient in English

6. Diagnosed non-diabetic as defined by the American Diabetes Association as any of the following recent (<3 months) findings:

1. Fasting glucose with a BGL <7.0 mmol/L
2. Glucose tolerance with a 2-hour BGL of < 11.1 mmol/L after a formal 75g Oral Glucose Tolerance Test (OGTT)
3. HbA1C of ≤ 6.5% 7. Possession or regular access to a mobile telephone with capability to download and run the Withings Sleep Anlayser App.

Exclusion Criteria:

1. Clinically significant co-morbidity (e.g. myocardial infarction, congestive heart failure, stroke, arrythmia, chronic kidney or liver disease, epilepsy, head injury)
2. 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.
3. Regular (>2 times per month) use of sleep-affecting medication (e.g. benzodiazepines, opioids, antidepressants)
4. Regular night shift work or travel overseas within the last 2 weeks
5. Sleep physician has advised against CPAP withdrawal
6. Pregnancy
7. 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
8. Current or previous diagnosis of diabetes mellitus (previous gestational diabetes mellitus not excluded)
9. Current or recent (<3 months) use of hypoglycaemic agents
10. Undergoing a weight loss programme
11. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: CPAP off condition; Participants will be monitored for a two-week period prior to commencing CPAP.
Experimental: CPAP on condition; Participants will be monitored for a two-week period at least four weeks following commencement of CPAP.	Device: CPAP; A positive CPAP intervention

What is the study measuring?

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	Difference in glucose tolerance as measured by peak 2-hour post 75g glucose load administered twice during each two-week observation period using a CGM	2 weeks
Coefficient of Variation	Percentage CV intraday (i.e. within 24h) and interday (i.e. over multiple days) between the CPAP on and CPAP off conditions as measured by the FreeStyle Libre Pro sensor during the 2-week intervention periods.	2 Weeks
SD of Mean Glucose	SD of Mean Glucose (daily) during the CPAP on and CPAP off conditions during the CPAP on and CPAP off conditions as measured by the FreeStyle Libre Pro sensor during the 2-week intervention periods.	2 Weeks
Time in Range (TIR)	Percentage of TIR (3.9-10.0 mmol/L) (hours and minutes) during the CPAP on and CPAP off conditions as measured by the FreeStyle Libre Pro sensor during the 2-week intervention periods.	2 Weeks
Time Below Range (TBR)	Percentage of TBR (3.9 mmol/L including readings of <3 .0 mmol/L) during the the CPAP on and CPAP off conditions as measured by the FreeStyle Libre Pro sensor during the 2-week intervention periods.	2 Weeks
Time below Range <3.0 mmol/L	Percentage of TBR <3.0 mmol/L (hours and minutes) during the CPAP on and CPAP off conditions as measured by the FreeStyle Libre Pro sensor during the 2-week intervention periods.	2 Weeks
Time Above Range (TAR)	Percentage of TAR (>10.0 mmol/L, including readings >13.9 mmol/L) (hours and minutes) during the CPAP on and CPAP off conditions as measured by the FreeStyle Libre Pro sensor during the 2-week intervention periods.	2 Weeks
Time Above Range >13.9 mmol/L	Percentage of TAR >13.9 mmol/L (hours and minutes) during the CPAP on and CPAP off conditions as measured by the FreeStyle Libre Pro sensor during the 2-week intervention periods.	2 Weeks
Time in Tight Range (TITR)	Percentage of TITR (3.9-7.8 mmol/L) (hours and minutes) during the CPAP on and CPAP off conditions as measured by the FreeStyle Libre Pro sensor during the 2-week intervention periods.	2 Weeks
Change in Glucose Management Indicator	Absolute main change in mmol/L or percentage during the CPAP on and CPAP off conditions as measured by the FreeStyle Libre Pro sensor during the 2-week intervention periods.	2 Weeks
Extended hypoglycaemic event rate	Number of events with sensor glucose <3.9 mmol/L lasting at least 120 min, event ends when glucose returns to at least 3.9 mmol/L for at least 15 minutes during the CPAP on and CPAP off conditions as measured by the FreeStyle Libre Pro sensor during the 2-week intervention periods.	2 Weeks
Extended hyperglycaemic event	Number of events with sensor glucose >13.9 mmol/L lasting at least 120 min; event ends when glucose returns to 10 mmol/L or less for at least 15 minutes during the CPAP on and CPAP off conditions as measured by the FreeStyle Libre Pro sensor during the 2-week intervention periods.	2 Weeks
TIR >70%	Proportion of participants with TIR 3.9-10.0 mmol/L for >70% of the day during the CPAP on and CPAP off conditions as measured by the FreeStyle Libre Pro sensor during the 2-week intervention periods.	2 Weeks
TIR improvement at least 5%	Proportion of participants with TIR 3.9-10.0 mmol/L with at least a 5% improvement from baseline during the CPAP on and CPAP off conditions as measured by the FreeStyle Libre Pro sensor during the 2-week intervention periods.	2 Weeks
TIR improvement at least 10%	Proportion of participants with TIR 3.9-10.0 mmol/L with at least a 10% improvement from baseline during the CPAP on and CPAP off conditions as measured by the FreeStyle Libre Pro sensor during the 2-week intervention periods.	2 Weeks
TBR <3.9 mmol/L <4%	Proportion of participants with TBR <3.9 mmol/L for <4% of each day during the CPAP on and CPAP off conditions as measured by the FreeStyle Libre Pro sensor during the 2-week intervention periods.	2 Weeks
TBR <3.0 mmol/L <1%	Proportion of participants with TBR <3.0 mmol/L for <1% of each day during the CPAP on and CPAP off conditions as measured by the FreeStyle Libre Pro sensor during the 2-week intervention periods.	2 Weeks
TAR >10.0 mmol/L >25%	Proportion of participants with a TAR >10.0 mmol/L for <25% of each day during the CPAP on and CPAP off conditions as measured by the FreeStyle Libre Pro sensor during the 2-week intervention periods.	2 Weeks
TAR >13.9 mmol/L <5%	Proportion of participants with TAR >13.9 mmol/L for <5% of each day during the CPAP on and CPAP off conditions as measured by the FreeStyle Libre Pro sensor during the 2-week intervention periods.	2 Weeks
Hypoglycaemia	Number of times CGM sensor values are <3.9 mmol/L (including readings of <3.0 mmol/L) for at least 15 consecutive minutes during the CPAP on and CPAP off conditions as measured by the FreeStyle Libre Pro sensor during the 2-week intervention periods. The event ends when there is at least 15 consecutive minutes with a CGM sensor value at least 3.9 mmol/L.	2 Weeks
Hypoglycaemia Alert Value (Level 1)	Number of times CGM sensor values are 3.0-3.9 mmol/L for at least 15 consecutive minutes during the CPAP on and CPAP off conditions as measured by the FreeStyle Libre Pro sensor during the 2-week intervention periods. The event ends when there is at least 15 consecutive minutes with a CGM sensor value at least 3.9 mmol/L.	2 Weeks
Clinically Significant Hypoglycaemia (Level 2)	Number of times CGM sensor values are <3.0 mmol/L for at least 15 consecutive minutes during the CPAP on and CPAP off conditions as measured by the FreeStyle Libre Pro sensor during the 2-week intervention periods. The event ends when there is at least 15 consecutive minutes with a CGM sensor value at least 3.0 mmol/L.	2 Weeks
Extended Hypoglycaemia	Number of times CGM sensor values are <3.9 mmol/L for at least 120 consecutive minutes during the CPAP on and CPAP off conditions as measured by the FreeStyle Libre Pro sensor during the 2-week intervention periods.	2 Weeks
High Glucose Level (Level 1)	Number of times CGM sensor values are 10.1-13.9 mmol/L for at least 15 consecutive minutes during the CPAP on and CPAP off conditions as measured by the FreeStyle Libre Pro sensor during the 2-week intervention periods. The event ends when there is at least 15 consecutive minutes with a CGM sensor value at or below 10 mmol/L.	2 Weeks
Very High Glucose (Level 2)	Number of times CGM sensor values are >13.9 mmol/L for at least 15 consecutive minutes during the CPAP on and CPAP off conditions as measured by the FreeStyle Libre Pro sensor during the 2-week intervention periods. The event ends when there is at least 15 consecutive minutes with a CGM sensor value at or below 13.9 mmol/L.	2 Weeks
Extended Hyperglycaemia	Number of times CGM sensor values are >13.9 mmol/L for at least 90 consecutive minutes within a 120-minute period during the CPAP on and CPAP off conditions as measured by the FreeStyle Libre Pro sensor during the 2-week intervention periods.	2 Weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
TIR Improvement >10% and <0.5% increase in TBR <3.0 mmol/L	Proportion of participants with >10% improvement in percentage of TIR 3.9-10.0 mmol/L without an increase in the TBR <3.0 mmol/L of >0.5% during the CPAP on and CPAP off conditions as measured by the FreeStyle Libre Pro sensor during the 2-week intervention periods.	2 Weeks
Mean Glucose <8.6 mmol/L and <1% TBR <3.0 mmol/L	Proportion of participants with Mean Glucose <8.6 mmol/L and < 1% TBR <3.0 mmol/L during the CPAP on and CPAP off conditions as measured by the FreeStyle Libre Pro sensor during the 2-week intervention periods.	2 Weeks
TIR >70% and <1% TBR <3.9 mmol/L	Proportion of participants with >70% TIR 3.9-10.0mmol/L and <4% TBR <3.9 mmol/L during the CPAP on and CPAP off conditions as measured by the FreeStyle Libre Pro sensor during the 2-week intervention periods.	2 Weeks
TIR >70% and < 1% TBR <3.0 mmol/L	Proportion of participants with >70% TIR 3.9-10.0 mmol/L and <1% TBR <3.0 mmol/L during the CPAP on and CPAP off conditions as measured by the FreeStyle Libre Pro sensor during the 2-week intervention periods.	2 Weeks

Collaborators and Investigators

• Sponsor: Woolcock Institute of Medical Research
• Investigators: Principal Investigator: Craig L Phillips, PhD, Woolcock Institute of Medical Research

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2025
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): February 28, 2027

Study Registration Dates

• First Submitted: April 12, 2022
• First Submitted That Met QC Criteria: April 12, 2022
• First Posted (Actual): April 19, 2022

Study Record Updates

• Last Update Posted (Actual): April 1, 2025
• Last Update Submitted That Met QC Criteria: March 25, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Nervous System Diseases; Metabolic Diseases; Respiratory Tract Diseases; Respiration Disorders; Glucose Metabolism Disorders; Diabetes Mellitus; Sleep Wake Disorders; Apnea; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Prediabetic State
• Other Study ID Numbers: 2021/ETH12082

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: All data will be deidentified using a unique study ID.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No