Hyperglycemic Profiles in Obstructive Sleep Apnea: Effects of PAP Therapy (HYPNOS)

This is a randomized control trial in people with diabetes and obstructive sleep apnea who will be randomly assigned for 3 months to PAP therapy along with healthy lifestyle and sleep education or healthy lifestyle and sleep education.

Study Overview

• Status: Completed
• Conditions: Diabetes; Sleep Apnea
• Intervention / Treatment: Device: REMStar Positive Airway Pressure; Behavioral: LifeStyle Counseling

Detailed Description

Research over the last decade has shown that obstructive sleep apnea (OSA) is a common condition in people with diabetes. Observational and experimental evidence also indicates that intermittent hypoxemia and recurrent arousals in OSA may alter glucose metabolism and worsen glycemic control. However, the impact of treating OSA with positive airway pressure (PAP) therapy on glycemic variability and control is not well defined. Adequately powered randomized clinical trials have yet to be performed to demonstrate whether PAP therapy for OSA in diabetics can improve glycemic variability (and control), decrease blood pressure, and reverse endothelial dysfunction. The overarching goal of this study is to determine whether PAP therapy for OSA in diabetics leads to improvements in (a) glycemic variability as assessed by self-monitoring of blood glucose and continuous monitoring of glucose; (b) glycosylated hemoglobin; (c) blood pressure; (d) endothelial function; (e) serum and urinary biomarkers; and (f) dyslipidemia.

• Study Type: Interventional
• Enrollment (Actual): 184
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins Bayview Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Type 2 diabetics
• Age > 21 and ≤ 75 years

Exclusion Criteria:

• Inability to consent or commit to the required visits
• Use of insulin or other injections for diabetes
• Weight change of 10% in last six months
• Use of oral steroids in the last six months
• Pulmonary disease (i.e., COPD)
• Renal or hepatic insufficiency
• Recent MI or stroke (< 3 months)
• Sleep-related hypoventilation
• Obesity-hypoventilation syndrome
• Morbid Obesity
• Occupation as a commercial driver or operator of heavy machinery
• Active substance use
• Untreated thyroid disease
• Pregnancy
• Any history of seizures or other neurologic disease
• Poor sleep hygiene or sleep disorder other than sleep apnea
• Central sleep apnea
• Variants of obstructive sleep apnea (e.g., REM-related OSA)
• Participants not suitable for the study based on the clinical judgment
• Use of any investigational drug within the past 30 days
• Participating in another study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: REMStar Positive Airway Pressure; Positive pressure therapy is the standard of care for managing obstructive sleep apnea.	Device: REMStar Positive Airway Pressure; Positive airway pressure therapy is the standard of care for managing obstructive sleep apnea
Other: LifeStyle Counseling; Lifestyle guidelines developed by the American Diabetes Association for weight loss will be provided to all subjects.	Behavioral: LifeStyle Counseling; Lifestyle guidelines developed by the American Diabetes Association for weight loss will be provided to all subjects.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Continuous Glucose Monitoring System Standard Deviation	Continuous Glucose Monitoring Metrics - change in standard deviation between baseline and three months.	Baseline and 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Difference in Systolic Blood Pressure	Mean difference between 3 months and baseline systolic blood pressures (in mmHg) by group.	Baseline and 3 months
Change in Endothelial Dysfunction as Assessed by the Reactive Hyperemic Index	Endothelial function was measured by the EndoPAT device - difference at 3 months - baseline, by group. The outcome reported is the Reactive Hyperemic Index (RHI). The RHI is a measure of endothelial vasodilator function. The RHI is the post-to-pre occlusion peripheral arterial tone signal ratio in the occluded arm relative to the other arm, which is not occluded. Persons with worse endothelial function have a lower RHI score. Consequently, a low RHI indicates more endothelial dysfunction. A value of 1.67 or less is considered abnormal vascular tone. The reported lower and upper limits in adults with type 2 diabetes is 1.1 - 4.9.	Baseline and 3 months
Heart Rate Variability		3 months
Change in the Epworth Sleepiness Scale	The Epworth Sleepiness Scale measures self-reported sleep propensity or daytime sleepiness. The range of the scale is 0 to 24 (integers only), with increasing values corresponding to increasing sleepiness. A cut-point of ≥ 11 is also sometimes used to differentiate those with pathological sleepiness (≥ 11) versus those without < 11. The difference between the three month final visit - the baseline visit score is reported by group	Baseline and 3 months
Change in Post-Pre Meal Blood Glucose Levels	The difference from baseline to three months in self-reported in blood glucose levels before and after meals (mg/dL) (post-meal - pre-meal). Data is presented for breakfast, lunch, and dinner.	Baseline and 3 months
Change in Glycosylated Hemoglobin A1c Level	Change in point-of-care hemoglobin A1c (%) after three months.	Baseline and 3 months
Continuous Glucose Monitoring System Mean Amplitude Glucose Excursion	Mean Amplitude Glucose Excursion in mg/dL (difference between the peaks and troughs of glucose from continuous glucose monitoring at three months).	3 months
Continuous Glucose Monitoring System Standard Deviation	The standard deviation of the glucose from continuous glucose monitoring at three months.	3 months
Change in Continuous Glucose Monitoring System Mean Glucose	Continuous Glucose Monitoring Metric - change in average glucose level (mg/dL) from baseline to three months.	Baseline and 3 months

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Naresh M Punjabi, MD, PhD, Johns Hopkins University

Publications and helpful links

General Publications

• Rooney MR, Aurora RN, Wang D, Selvin E, Punjabi NM. Rationale and design of the Hyperglycemic Profiles in Obstructive Sleep Apnea (HYPNOS) trial. Contemp Clin Trials. 2021 Feb;101:106248. doi: 10.1016/j.cct.2020.106248. Epub 2020 Dec 11.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2014
• Primary Completion (Actual): March 15, 2020
• Study Completion (Actual): March 15, 2020

Study Registration Dates

• First Submitted: January 14, 2015
• First Submitted That Met QC Criteria: May 26, 2015
• First Posted (Estimate): May 27, 2015

Study Record Updates

• Last Update Posted (Actual): May 25, 2021
• Last Update Submitted That Met QC Criteria: May 3, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Apnea
• Other Study ID Numbers: NA_00093188; R01HL117167 (U.S. NIH Grant/Contract)