CPAP Withdrawal and Glucose Metabolism in OSA With Pre-diabetes

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

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

Study Overview

• Status: Recruiting
• Conditions: Obstructive Sleep Apnea; Pre-diabetes
• Intervention / Treatment: Device: CPAP withdrawal

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 36
• 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
    • Glebe, New South Wales, Australia, 2095
      • Recruiting
      • Woolcock Institute of Medical Research
      • Contact: Grigori Kaplan, PhD; Phone Number: +61 9114 0412; Email: grigori.kaplan@sydney.edu.au
      • Principal Investigator: Craig Phillips, PhD
      • Principal Investigator: Keith Wong, PhD FRACP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

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 24 months
3. Able to give written informed consent
4. Proficient in English
5. 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.

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

   1. Impaired fasting glucose with a BGL of 5.6 to 6.9 mmol/L
   2. 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)
   3. HbA1C of 5.7% to 6.4%
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: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CPAP on condition; 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; A negative CPAP intervention
Experimental: CPAP off condition; 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; A negative 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 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

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 (Actual): January 31, 2023
• Primary Completion (Estimated): December 14, 2023
• Study Completion (Estimated): December 14, 2023

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): September 22, 2023
• Last Update Submitted That Met QC Criteria: September 19, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Endocrine System Diseases; Hyperglycemia; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Diabetes Mellitus; Prediabetic State; Glucose Intolerance
• 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