Obstructive Sleep Apnea and Glucose Metabolism

Sleep Apnea Clinical Trial

— OSAGM  

Official title:

Obstructive Sleep Apnea and Glucose Metabolism

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT03408613
• Other study ID #: 201710015
• Status: Suspended
• Phase: N/A
• Start date: January 17, 2018
• Est. completion date: February 2025

Study information

• Verified date: January 2024
• Source: University of Missouri-Columbia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 80
• Est. completion date: February 2025
• Est. primary completion date: February 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 30 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Apnea
• Glucose Metabolism Disorders
• Metabolic Diseases
• Sleep Apnea
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive

Intervention

Procedure:
• Positive Airway Pressure
See arm/group description
• Supplemental Oxygen
See arm/group description
• Sham
See arm/group description

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
University of Missouri-Columbia

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	ß-cell function	ß-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.	3 months
Secondary	Tissue oxygenation	Adipose and muscle tissue oxygenation, expressed as mmHg, will be evaluated in situ during the hyperinsulinemic-euglycemic clamp studies.	3 months
Secondary	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.	3 months