Metabolic Endpoints for Obstructive Sleep Apnea Following Twelfth Cranial Nerve Stimulation

Obstructive Sleep Apnea Clinical Trial

Official title:

Hgns: Metabolic Endpoints For Obstructive Sleep Apnea Following Twelfth Cranial Nerve Stimulation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06317701
• Other study ID #: IRB23-1801
• Status: Recruiting
• Start date: April 4, 2024
• Est. completion date: April 2028

Study information

• Verified date: April 2024
• Source: University of Chicago
• Contact: Phillip LoSavio, MD, MS
• Phone: 773-702-5189
• Email: Phillip.Losavio[@]bsd.uchicago.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: April 2028
• Est. primary completion date: April 2028
• Gender: All
• Age group: 18 Years and older

Eligibility

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
• Absent circumferential collapse on Drug-Induced Sleep Endoscopy (DISE)
• Not able to use positive airway pressure >4 hours for 5 nights/week or unwilling to use positive airway pressure
• Weight stable (no change >25 lbs in the past 3 months)

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)
• Enrolled in a formal weight loss program or following an incompatible dietary regimen
• Current systemic steroid use
• Taking prescription medication or herbal remedy for weight loss
• 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

Related Conditions & MeSH terms

• Apnea
• Obstructive Sleep Apnea
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive

Intervention

Device:
• Hypoglossal Nerve Stimulation (HGNS)
Alternative therapy for Obstructive Sleep Apnea

Locations

Country	Name	City	State
United States	The University of Chicago	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
University of Chicago

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Glycemic variability	measured by standard deviation (SD) of average blood glucose or % coefficient of variation (SD / mean glucose) on two-week continuous glucose monitor	at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-op
Primary	Mean systolic BP (daytime and nocturnal)	important mediators of cardiovascular outcomes	24 hrs at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-op
Primary	Glycemic variability	measured by standard deviation (SD) of % coefficient of variation (SD / mean glucose) on two-week continuous glucose monitor	at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-op
Secondary	mean blood glucose levels	other glycemic metrics for the clinical care of diabetes to be followed.	at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op
Secondary	mean ambulatory glucose excursions	glycemic metrics for the clinical care of diabetes will be followed	at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op
Secondary	time blocks	glycemic metrics for the clinical care of diabetes will be followed	24-h, day, night at baseline and after HGNS implant, acclimation, and tuning
Secondary	Morning fasting insulin, including calculated insulin resistance (HOMA-IR)		at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op
Secondary	Mean norepinephrine levels		at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op
Secondary	Morning fasting blood glucose	markers of glucose metabolism	at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op
Secondary	Hemoglobin A1c	markers of glucose metabolism	at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op
Secondary	Insulin levels	markers of glucose metabolism	at baseline and after HGNS implant, acclimation, and tuning
Secondary	c-peptide levels	markers of glucose metabolism	at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op
Secondary	fasting lipid profile (triglycerides)	testing for signs of cardiovascular disease	at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op
Secondary	heart rate indices by activity monitor	testing for signs of cardiovascular disease	at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op
Secondary	sympathetic activity by plasma norepinephrine	to investigate its role as a mediator in cardiometabolic response to treatment	at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op
Secondary	Morning fasting insulin of c-peptide level		at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op
Secondary	fasting lipid profile (HDL- cholesterol)	testing for signs of cardiovascular disease	at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op
Secondary	fasting lipid profile ( LDL-cholesterol)	testing for signs of cardiovascular disease	at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op