Obstructive Sleep Apnea
Conditions
Brief summary
The purpose of this study is to determine if the treatment of Obstructive sleep apnea (OSA) by hypoglossal nerve stimulation (HGNS) will alter glucose metabolism. The study team will also determine if the treatment of Obstructive sleep apnea (OSA) by (hypoglossal nerve stimulation) HGNS will alter predictors of cardiovascular outcomes.
Detailed description
Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder in the general population. It is estimated that 80 percent of those who have OSA remain undiagnosed, and thus do not receive therapy. Strong evidence from epidemiologic and clinical studies suggests that untreated OSA is an independent risk factor for cardiometabolic disease, particularly among those with moderate-to-severe OSA. Animal and human models have revealed that intermittent hypoxia and sleep fragmentation (i.e., main features of OSA) result in insulin resistance, glucose intolerance and pancreatic beta-cell dysfunction, hypertension and dyslipidemia. Continuous positive airway pressure (CPAP) is the established first-line treatment for OSA. However, only 50% of patients with OSA are adherent to CPAP therapy. Notably, a key limitation of prior CPAP trials on cardiometabolic outcomes is low treatment adherence. A randomized controlled trial conducted at the University of Chicago demonstrated that 8 hours of nightly CPAP reduces glucose response during oral glucose tolerance testing and improves insulin sensitivity in individuals with OSA and prediabetes. In 2014, following the pivotal Safe and Timely Antithrombotic Removal - Ticagrelor trial (STAR), the Food and Drug Administration (FDA) approved hypoglossal nerve stimulation (HNS) as an alternative therapy for OSA. Five-year outcomes from STAR have confirmed durable efficacy, tolerance, and safety for HNS. From improved tolerance and adherence, it is theorized that HNS may be more effective than CPAP at ameliorating cardiovascular and diabetes risk. Yet, there is no literature on the cardiometabolic outcomes of treating OSA with HNS. The study team's long-term goal is to understand the metabolic and cardiovascular effects of OSA and how current therapies can mitigate risk and improve outcomes. The overall objective of this study is to determine the cardiometabolic impact of HNS therapy in patients with moderate-to-severe OSA who are intolerant to CPAP. It is hypothesized by the investigator that effective HNS treatment will improve glucose metabolism and markers of cardiovascular disease.
Interventions
DEVICEHypoglossal Nerve Stimulation (HGNS)
Alternative therapy for Obstructive Sleep Apnea
Sponsors
University of Chicago
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Overweight or obese males and females BMI 25 kg/m2 to 40 kg/m2 * Age 18 years and older * Diagnosed with obstructive sleep apnea by Apnea-Hypopnea Index \>15 events/hr using 4% oxygen desaturation criteria and \< 25% central events/hr on prior sleep testing Data can be derived from home sleep testing or in-lab polysomnogram * Not able to use positive airway pressure \>4 hours for 5 nights/week or unwilling to use positive airway pressure
Exclusion criteria
* Insulin-dependent Diabetes * Inability to undergo in-lab polysomnography or home sleep testing * Central Nervous System (CNS) disease with impairment of cognitive function (dementia) and/or muscle paresis, such as stroke * Currently pregnant, trying to get pregnant or nursing * age \< 18 years * Regular and adherent CPAP use per clinical guidelines * Current night shift or rotating shift work * Diagnosis of another sleep disorder (e.g. periodic limb movement disorder) * Current systemic steroid use * Predominantly central sleep apnea or requiring oxygen or bi-level positive airway pressure or advanced positive airway pressure modalities * Protected patient: under guardianship, curatorship or other legal protection, deprived of liberty by judicial or administrative decision, including hospitalized without consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Glycemic variability | at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-op | measured by standard deviation (SD) of average blood glucose or % coefficient of variation (SD / mean glucose) on two-week continuous glucose monitor |
| Mean systolic BP (daytime and nocturnal) | 24 hrs at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-op | important mediators of cardiovascular outcomes |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| mean blood glucose levels | at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op | other glycemic metrics for the clinical care of diabetes to be followed. |
| mean ambulatory glucose excursions | at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op | glycemic metrics for the clinical care of diabetes will be followed |
| time blocks | 24-h, day, night at baseline and after HGNS implant, acclimation, and tuning | glycemic metrics for the clinical care of diabetes will be followed |
| Morning fasting insulin, including calculated insulin resistance (HOMA-IR) | at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op | — |
| Mean norepinephrine levels | at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op | — |
| Morning fasting blood glucose | at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op | markers of glucose metabolism |
| Hemoglobin A1c | at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op | markers of glucose metabolism |
| Insulin levels | at baseline and after HGNS implant, acclimation, and tuning | markers of glucose metabolism |
| c-peptide levels | at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op | markers of glucose metabolism |
| fasting lipid profile (triglycerides) | at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op | testing for signs of cardiovascular disease |
| heart rate indices by activity monitor | at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op | testing for signs of cardiovascular disease |
| sympathetic activity by plasma norepinephrine | at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op | to investigate its role as a mediator in cardiometabolic response to treatment |
| Morning fasting insulin of c-peptide level | at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op | — |
| fasting lipid profile (HDL- cholesterol) | at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op | testing for signs of cardiovascular disease |
| fasting lipid profile ( LDL-cholesterol) | at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op | testing for signs of cardiovascular disease |
Countries
United States
Contacts
CONTACTPhillip LoSavio, MD, MS
CONTACTCarlisa Dixon
PRINCIPAL_INVESTIGATORPhillip LoSavio, MD, MS
University of Chicago
Outcome results
None listed