search
Back to results

Obstructive Sleep Apnea and Glucose Metabolism (OSAGM)

Primary Purpose

Sleep Apnea, Glucose Metabolism Disorders

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Positive Airway Pressure
Supplemental Oxygen
Sham
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sleep Apnea focused on measuring Obstructive Sleep Apnea, Glucose Metabolism

Eligibility Criteria

30 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

General Inclusion Criteria (for all subjects):

  • 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%)

Sleep-related inclusion criteria:

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.

General Exclusion Criteria (for all subjects):

  • 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

Sites / Locations

  • Washington University School of MedicineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Sham Comparator

No Intervention

Arm Label

Positive Airway Pressure (PAP)

Supplemental Oxygen (O2)

Sham

Controls

Arm Description

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.

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..

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.

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

β-cell function
β-cell responsivity to glucose and the disposition index will be determined to characterize the insulin secretory response to glucose infusion and the relationship between insulin secretion and insulin sensitivity. This outcome will be determined by using an insulin-modified intravenous glucose tolerance test in conjunction with mathematical modelling and insulin sensitivity data from the hyperinsulinemic clamp.
Tissue oxygenation
Adipose and muscle tissue oxygenation, expressed as mmHg, will be evaluated in situ during the hyperinsulinemic-euglycemic clamp studies.
Body composition analysis
Detailed body composition analysis using dual energy x-ray absorptiometry (DXA) will provide the researchers with total and appendicular lean body and fat mass, expressed in grams of participants.

Full Information

First Posted
December 1, 2017
Last Updated
June 16, 2023
Sponsor
Washington University School of Medicine
search

1. Study Identification

Unique Protocol Identification Number
NCT03408613
Brief Title
Obstructive Sleep Apnea and Glucose Metabolism
Acronym
OSAGM
Official Title
Obstructive Sleep Apnea and Glucose Metabolism
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 17, 2018 (Actual)
Primary Completion Date
February 2024 (Anticipated)
Study Completion Date
February 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Washington University School of Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sleep Apnea, Glucose Metabolism Disorders
Keywords
Obstructive Sleep Apnea, Glucose Metabolism

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Positive Airway Pressure (PAP)
Arm Type
Experimental
Arm Description
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.
Arm Title
Supplemental Oxygen (O2)
Arm Type
Experimental
Arm Description
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..
Arm Title
Sham
Arm Type
Sham Comparator
Arm Description
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.
Arm Title
Controls
Arm Type
No Intervention
Arm Description
Subjects without OSA will be recruited and complete all testing for primary outcome measures, but will not undergo any intervention.
Intervention Type
Procedure
Intervention Name(s)
Positive Airway Pressure
Intervention Description
See arm/group description
Intervention Type
Procedure
Intervention Name(s)
Supplemental Oxygen
Intervention Description
See arm/group description
Intervention Type
Procedure
Intervention Name(s)
Sham
Intervention Description
See arm/group description
Primary Outcome Measure Information:
Title
Insulin mediated glucose disposal
Description
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.
Time Frame
3 months
Secondary Outcome Measure Information:
Title
β-cell function
Description
β-cell responsivity to glucose and the disposition index will be determined to characterize the insulin secretory response to glucose infusion and the relationship between insulin secretion and insulin sensitivity. This outcome will be determined by using an insulin-modified intravenous glucose tolerance test in conjunction with mathematical modelling and insulin sensitivity data from the hyperinsulinemic clamp.
Time Frame
3 months
Title
Tissue oxygenation
Description
Adipose and muscle tissue oxygenation, expressed as mmHg, will be evaluated in situ during the hyperinsulinemic-euglycemic clamp studies.
Time Frame
3 months
Title
Body composition analysis
Description
Detailed body composition analysis using dual energy x-ray absorptiometry (DXA) will provide the researchers with total and appendicular lean body and fat mass, expressed in grams of participants.
Time Frame
3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
General Inclusion Criteria (for all subjects): 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%) Sleep-related inclusion criteria: 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. General Exclusion Criteria (for all subjects): 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Bettina Mittendorfer, PhD
Phone
3143628450
Email
mittendb@wustl.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bettina Mittendorfer, PhD
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bettina Mittendorfer, PhD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35577100
Citation
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.
Results Reference
derived
PubMed Identifier
32651241
Citation
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.
Results Reference
derived

Learn more about this trial

Obstructive Sleep Apnea and Glucose Metabolism

We'll reach out to this number within 24 hrs