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

• ClinicalTrials.gov Identifier: NCT02454153
• Recruitment Status: Completed
• First Posted: May 27, 2015
• Results First Posted: May 25, 2021
• Last Update Posted: May 25, 2021
• Sponsor: Johns Hopkins University
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): Johns Hopkins University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Sleep Apnea; Diabetes	Device: REMStar Positive Airway Pressure; Behavioral: LifeStyle Counseling	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 184 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Hyperglycemic Profiles in Obstructive Sleep Apnea: Effects of PAP Therapy
• Actual Study Start Date: December 2014
• Actual Primary Completion Date: March 15, 2020
• Actual Study Completion Date: March 15, 2020

Arms and Interventions

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
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.

Outcome Measures

Primary Outcome Measures :

1. Change in Continuous Glucose Monitoring System Standard Deviation [ Time Frame: Baseline and 3 months ]
   Continuous Glucose Monitoring Metrics - change in standard deviation between baseline and three months.

Secondary Outcome Measures :

1. Mean Difference in Systolic Blood Pressure [ Time Frame: Baseline and 3 months ]
   Mean difference between 3 months and baseline systolic blood pressures (in mmHg) by group.
2. Change in Endothelial Dysfunction as Assessed by the Reactive Hyperemic Index [ Time Frame: Baseline and 3 months ]
   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.
3. Heart Rate Variability [ Time Frame: 3 months ]
4. Change in the Epworth Sleepiness Scale [ Time Frame: Baseline and 3 months ]
   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
5. Change in Post-Pre Meal Blood Glucose Levels [ Time Frame: Baseline and 3 months ]
   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.
6. Change in Glycosylated Hemoglobin A1c Level [ Time Frame: Baseline and 3 months ]
   Change in point-of-care hemoglobin A1c (%) after three months.
7. Continuous Glucose Monitoring System Mean Amplitude Glucose Excursion [ Time Frame: 3 months ]
   Mean Amplitude Glucose Excursion in mg/dL (difference between the peaks and troughs of glucose from continuous glucose monitoring at three months).
8. Continuous Glucose Monitoring System Standard Deviation [ Time Frame: 3 months ]
   The standard deviation of the glucose from continuous glucose monitoring at three months.
9. Change in Continuous Glucose Monitoring System Mean Glucose [ Time Frame: Baseline and 3 months ]
   Continuous Glucose Monitoring Metric - change in average glucose level (mg/dL) from baseline to three months.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Maryland

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, United States, 21224

Sponsors and Collaborators

Johns Hopkins University

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Naresh M Punjabi, MD, PhD; Johns Hopkins University

  Study Documents (Full-Text)

Documents provided by Johns Hopkins University:

Study Protocol and Statistical Analysis Plan  [PDF] March 30, 2017

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT02454153
• Other Study ID Numbers: NA_00093188; R01HL117167 ( U.S. NIH Grant/Contract )
• First Posted: May 27, 2015
• Results First Posted: May 25, 2021
• Last Update Posted: May 25, 2021
• Last Verified: May 2021

Additional relevant MeSH terms:

Apnea; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases