Metabolic Endpoints for Obstructive Sleep Apnea Following Twelfth Cranial Nerve Stimulation

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.

• mean blood glucose levels [Срок оценки: at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op]
• mean ambulatory glucose excursions [Срок оценки: at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op]
• time blocks [Срок оценки: 24-h, day, night at baseline and after HGNS implant, acclimation, and tuning]
• Morning fasting insulin, including calculated insulin resistance (HOMA-IR) [Срок оценки: at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op]
• Mean norepinephrine levels [Срок оценки: at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op]
• Morning fasting blood glucose [Срок оценки: at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op]
• Hemoglobin A1c [Срок оценки: at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op]
• Insulin levels [Срок оценки: at baseline and after HGNS implant, acclimation, and tuning]
• c-peptide levels [Срок оценки: at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op]
• fasting lipid profile (triglycerides) [Срок оценки: at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op]
• heart rate indices by activity monitor [Срок оценки: at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op]
• sympathetic activity by plasma norepinephrine [Срок оценки: at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op]