Metabolic Impact of Intermittent CPAP (MIIC)

Obstructive sleep apnea is a risk factor for diabetes and cardiovascular disease, by unknown mechanisms. The investigators hypothesize that sleep apnea changes glucose and lipid metabolism during sleep, which over time could lead to diabetes and cardiovascular disease. This study examines metabolic changes during sleep in patients with obstructive sleep apnea. Patients accustomed to continuous positive airway pressure (CPAP) therapy are enrolled to undergo sleep studies, either on CPAP therapy or after withdrawing from CPAP for 3 nights. During sleep, blood samples are obtained so that metabolic function can be compared between sleep apnea and CPAP nights.

Study Overview

• Status: Completed
• Conditions: Obstructive Sleep Apnea
• Intervention / Treatment: Other: CPAP withdrawal

Detailed Description

Participants with a history of moderate severe sleep apnea (AHI>20) will be enrolled if participants meet inclusion/exclusion criteria. Investigators will report to the sleep laboratory on two nights, (1) after continuing their CPAP or (2) after discontinuing CPAP for 3 nights. The order of observation will be randomized. A standard research dinner is provided before each study. IV's are placed so that blood can be sampled at frequent (30 min) intervals throughout the night. In the morning after each study, a glucose tolerance test and endothelial function study (endoPAT) are performed. Serum samples will be analyzed for glucose, insulin, free fatty acids, triglycerides, hormones, and other metabolic biomarkers.

• Study Type: Interventional
• Enrollment (Actual): 144
• 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: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• History of moderate to severe Obstructive sleep apnea (OSA) (AHI or respiratory disturbance index (RDI)> 10).
• They must also own a CPAP machine and report the ability to tolerate sleeping with or without CPAP during the night.

Exclusion Criteria:

• Uncontrolled hypertension with systolic blood pressure >170 or diastolic blood pressure > 110
• Congestive heart failure
• Use of clonidine or nicotinic acid medication
• Diabetes requiring the use of insulin
• Known pregnancy, by urine testing in women of child-bearing age
• History of falling asleep while driving, near miss
• High risk occupation (pilot, commercial driver)
• Hemoglobin < 10 g/dL on point of care screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: CPAP (Usual care); Continuation of established CPAP therapy. CPAP will be worn during a metabolic sleep study in the research laboratory.
Experimental: CPAP withdrawal; Cessation of established CPAP therapy for 3 nights. CPAP will NOT be worn during this period, and a metabolic sleep study off CPAP is performed in the research laboratory on the third night.	Other: CPAP withdrawal; CPAP is discontinued for 3 nights.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of Plasma Free Fatty Acids (FFA, mmol/L)	We will report the mean for all participants per group (CPAP vs. CPAP withdrawal).	2 nights, <1 month apart. Data from each night was averaged to report a single value.
Concentration of Plasma Glucose (mg/dl)	We will report the mean for all participants per group (CPAP vs. CPAP withdrawal).	2 nights, <1 month apart. Data from each night was averaged to report a single value.
Concentration of Plasma Insulin (mcU/ml)	We will report the mean for all participants per group (CPAP vs. CPAP withdrawal).	2 nights, <1 month apart. Data from each night was averaged to report a single value.
Concentration of Plasma Triglycerides (mg/dl)	We will report the mean for all participants per group (CPAP vs. CPAP withdrawal).	2 nights, <1 month apart. Data from each night was averaged to report a single value.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oral Glucose Tolerance Test (OGTT)	We will report the mean of the area under the curve (AUC) during OGTT for all participants per group (CPAP vs. CPAP withdrawal).	2 nights, <1 month apart. 5 OGTT values were averaged to a obtain a single value.
Reactive Hyperemia Index (RHI)	Measured in the morning using Itamar EndoPAT device. This will measure the ratio of blood flow after brachial artery occlusion to blood flow prior to brachial artery occlusion. Normal values range from approximately 1 to 3 with higher values being associated with better vascular function. We will report the mean for all participants per group (CPAP vs. CPAP withdrawal).	2 nights, <1 month apart, 1 measurement each visit
Augmentation Index (AI)	Measured in the morning using Itamar EndoPAT device. Augmentation index is measured once during each visit, and is expressed as a % increase in the pressure waveform during systole. We will report the mean for all participants per group (CPAP vs. CPAP withdrawal).	2 nights, <1 month apart, 1 measurement each visit

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); American Academy of Sleep Medicine
• Investigators: Principal Investigator: Jonathan C Jun, MD, Johns Hopkins University

Publications and helpful links

General Publications

• Chopra S, Rathore A, Younas H, Pham LV, Gu C, Beselman A, Kim IY, Wolfe RR, Perin J, Polotsky VY, Jun JC. Obstructive Sleep Apnea Dynamically Increases Nocturnal Plasma Free Fatty Acids, Glucose, and Cortisol During Sleep. J Clin Endocrinol Metab. 2017 Sep 1;102(9):3172-3181. doi: 10.1210/jc.2017-00619.

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2016
• Primary Completion (Actual): December 1, 2022
• Study Completion (Actual): December 1, 2022

Study Registration Dates

• First Submitted: March 18, 2016
• First Submitted That Met QC Criteria: June 30, 2016
• First Posted (Estimated): July 6, 2016

Study Record Updates

• Last Update Posted (Estimated): January 1, 2024
• Last Update Submitted That Met QC Criteria: December 12, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: obstructive sleep apnea; CPAP; metabolism
• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Sleep Apnea Syndromes; Sleep Apnea, Obstructive
• Other Study ID Numbers: NA_00086830; R01HL135483 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No