Obstructive Sleep Apnea and Glucose Metabolism

NCT ID: NCT03408613

Last Updated: 2025-03-25

Basic Information

• Recruitment Status: SUSPENDED
• Clinical Phase: NA
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-17
• Study Completion Date: 2028-02-29

Brief Summary

Many adults who are overweight have obstructive sleep apnea (OSA) which disrupts sleep and makes it difficult to breath during the night. OSA increases the risk for a person to become insulin resistant and diabetic. It is not known why OSA causes this problem, i.e., whether it is disrupted sleep or lack of oxygen., which can change how the body handles glucose in adipose tissue, muscle tissue and liver.

The purpose of this research study is to determine the key issues and mechanisms responsible for dysregulated glucose metabolism in people with OSA. The investigators will do this by comparing glucose metabolism in people who have OSA, and those who do not, and by evaluating the effect of treating OSA by providing continuous positive airway pressure (CPAP) or simply oxygen during the night.

The proposed study will evaluate the primary causes(s) (hypoxia, sleep fragmentation, or both) and pathophysiological mechanisms responsible for the OSA-associated metabolic abnormalities. Knowing the primary cause of Obstructive Sleep Apnea and pathophysiological mechanisms responsible for the OSA-associated metabolic abnormalities could help develop potentially novel therapeutic strategies to provide treatment for adults in improving OSA and associated comorbidities.

Conditions

Sleep Apnea; Glucose Metabolism Disorders

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Positive Airway Pressure (PAP)

A registered polysomnographic technologist will perform a titration starting at 4 cm water (H2O) and adjust this value as needed to identify the optimal pressure to achieve an Apnea Hypopnea Index (AHI) \<5 (including rapid eye movement sleep in the supine position). After PAP titration, subjects will be instructed to use the machine at the optimal pressure every night for 3 months. Compliance will be defined as: ≥4 hours use on 70% of nights and average use ≥6 hours per night.

Group Type: EXPERIMENTAL

Positive Airway Pressure

Intervention Type: PROCEDURE

See arm/group description

Supplemental Oxygen (O2)

Subjects randomized to night-time supplemental oxygen will complete an overnight oxygen titration protocol in the clinical research unit. Initially, subjects will receive 0.5 liters oxygen (O2)/min; the delivery rate will then be increased by 0.5 l/min until oxygen saturation (SaO2) is ≥88%. The optimal O2 delivery rate determined during this study will be used for the intervention. The oxygen concentrators used at home will record cumulative hours of use to provide an objective measure of adherence (monitored weekly). Compliance will be defined as ≥6 h average use per night..

Group Type: EXPERIMENTAL

Supplemental Oxygen

Intervention Type: PROCEDURE

See arm/group description

Sham

Subjects in the sham treatment group will complete the oxygen titration protocol described for the night-time supplemental oxygen group, except that their oxygen concentrator will have been covertly modified to deliver room air at a rate of 0.5 l/min.

Group Type: SHAM_COMPARATOR

Sham

Intervention Type: PROCEDURE

See arm/group description

Controls

Subjects without OSA will be recruited and complete all testing for primary outcome measures, but will not undergo any intervention.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Positive Airway Pressure

See arm/group description

Intervention Type: PROCEDURE

Supplemental Oxygen

See arm/group description

Intervention Type: PROCEDURE

Sham

See arm/group description

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Age: ≥30 and ≤70 years,
• BMI: ≥30 and ≤45 kg/m2 or body fat ≥ 30 % for women and ≥ 25 % for men,
• Maximum body circumference <170 cm
• Weight stable (≤2% change)
• Untrained (≤1 h of structured exercise/wk) for at least 3 months before entering the study
• No diabetes (fasting blood glucose <126 mg/dl, 2h oral glucose tolerance test (OGTT) glucose <200 mg/dl, HbA1c ≤6.5%)

Subjects without OSA:

• AHI <5/h of sleep;
• Oxygen desaturation index <3/h
• No known sleep disorders and periodic limb movement arousal index <15/h during polysomnography
• Reported sleep duration ≥6 h per night
• Regular sleep schedules (i.e. bedtime between 8 pm and 12 am and wake-time between 4 am and 8 am on all days of the week)

Subjects with OSA

• AHI ≥10/h of sleep (i.e., moderate to severe OSA)
• Oxygen desaturation index ≥4/h;
• No polysomnogram finding that would trigger immediate PAP treatment as per standard operating protocol in our sleep medicine center (a single SaO2 <50%, SaO2 <70% for >2 minutes, electrocardiogram pause >5 sec, or ventricular tachycardia >30 sec), because of the risk of a potentially adverse outcome if they are not randomized to the PAP group
• Periodic limb movement arousal index <15/h during polysomnography,
• Reported sleep duration ≥6 h per night,
• Regular night-time sleep schedules, defined as bedtime between 8 pm and 12 am and wake-time between 4 am and 8 am on all days of the week.

Exclusion Criteria

• Current treatment for previously diagnosed OSA;
• Self-reported severe difficulty sleeping in unfamiliar environments;
• Metal implants that are incompatible with magnetic resonance imaging;
• Controlled substances, tobacco products, dietary supplements, or medications known or suspected to affect sleep, breathing, upper airway muscle physiology, or glucose metabolism
• Evidence of disease (e.g., diabetes, congestive heart failure; chronic obstructive pulmonary disease; hypoventilation, defined as daytime partial pressure of carbon dioxide (pCO2) >45 mm Hg; major neurological or neuromuscular disorders; cancer; uncontrolled hypertension; etc.);
• Contraindications to supplemental oxygen or PAP (e.g., recent trans-sphenoidal surgery).
• Unwillingness or inability to provide informed consent
• Study physician considers subject to be unable to safely complete the study protocol

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Missouri-Columbia

OTHER

Sponsor Role: lead

Responsible Party

Bettina Mittendorfer

Senior Associate Dean for Research

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Bettina Mittendorfer, PhD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Countries

United States

References

Cao C, Koh HE, Van Vliet S, Patterson BW, Reeds DN, Laforest R, Gropler RJ, Mittendorfer B. Increased plasma fatty acid clearance, not fatty acid concentration, is associated with muscle insulin resistance in people with obesity. Metabolism. 2022 Jul;132:155216. doi: 10.1016/j.metabol.2022.155216. Epub 2022 May 13.

Reference Type: DERIVED

PMID: 35577100 (View on PubMed)

van Vliet S, Koh HE, Patterson BW, Yoshino M, LaForest R, Gropler RJ, Klein S, Mittendorfer B. Obesity Is Associated With Increased Basal and Postprandial beta-Cell Insulin Secretion Even in the Absence of Insulin Resistance. Diabetes. 2020 Oct;69(10):2112-2119. doi: 10.2337/db20-0377. Epub 2020 Jul 10.

Reference Type: DERIVED

PMID: 32651241 (View on PubMed)

Other Identifiers

201710015

Identifier Type: -

Identifier Source: org_study_id