Obstructive Sleep Apnea and Glucose Metabolism (OSAGM)

University of Missouri (MU)

Status: Suspended

Conditions: Glucose Metabolism Disorders; Sleep Apnea

Treatments: Procedure: Sham; Procedure: Positive Airway Pressure; Procedure: Supplemental Oxygen

Study type: Interventional

Funder types: Other

Identifiers

NCT03408613

201710015

Details and patient eligibility

About

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.

Enrollment: 80 estimated patients

Sex: All

Ages: 30 to 70 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

---

80 participants in 4 patient groups

Positive Airway Pressure (PAP)

Experimental group

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.

Treatment:

Procedure: Positive Airway Pressure

Supplemental Oxygen (O2)

Experimental group

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..

Treatment:

Procedure: Supplemental Oxygen

Sham

Sham Comparator group

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.

Treatment:

Procedure: Sham

Controls

No Intervention group

Description:

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