Obstructive Sleep Apnea and Glucose Metabolism

NCT03408613 | Suspended DMC

• 1 other identifier: 201710015
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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

Keywords

Obstructive Sleep Apnea; Glucose Metabolism

Outcome Measures

Primary Outcomes (1)

• Insulin mediated glucose disposal

  The hyperinsulinemic-euglycemic clamp technique combined with isotope-labelled tracer infusions will be used to assess insulin mediated glucose rate of disappearance before and after treatment of OSA with three months of night-time supplemental oxygen, PAP, or sham.

  3 months

Secondary Outcomes (3)

• β-cell function

  3 months

• Tissue oxygenation

  3 months

• Body composition analysis

  3 months

Study Arms (4)

Positive Airway Pressure (PAP)

EXPERIMENTAL

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.

Procedure: Positive Airway Pressure

Supplemental Oxygen (O2)

EXPERIMENTAL

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..

Procedure: Supplemental Oxygen

Sham

SHAM COMPARATOR

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.

Procedure: Sham

Controls

NO INTERVENTION

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

Interventions

Positive Airway Pressure PROCEDURE

See arm/group description

Positive Airway Pressure (PAP)

Supplemental Oxygen PROCEDURE

See arm/group description

Supplemental Oxygen (O2)

Sham PROCEDURE

See arm/group description

Sham

Eligibility Criteria

• Age: 30 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Missouri-Columbia: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (2)

• 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.

  PMID: 35577100 DERIVED

• 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.

  PMID: 32651241 DERIVED

MeSH Terms

Conditions

Sleep Apnea Syndromes; Glucose Metabolism Disorders; Sleep Apnea, Obstructive

Interventions

salicylhydroxamic acid

Condition Hierarchy (Ancestors)

Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Bettina Mittendorfer, PhD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Associate Dean for Research

Study Record Dates

• First Submitted: December 1, 2017
• First Posted: January 24, 2018
• Study Start: January 17, 2018
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2028
• Last Updated: March 25, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)