Metabolic Endpoints for Obstructive Sleep Apnea Following Twelfth Cranial Nerve Stimulation

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

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.

Study Overview

• Status: Recruiting
• Conditions: Obstructive Sleep Apnea
• Intervention / Treatment: Device: Hypoglossal Nerve Stimulation (HGNS)

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.

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: Carlisa Dixon; Phone Number: 773-834-4337; Email: cdixon520@bsd.uchicago.edu
• Study Contact Backup: Name: Phillip LoSavio, MD, MS; Phone Number: 773-702-5189; Email: Phillip.Losavio@bsd.uchicago.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • The University of Chicago
      • Contact: Leila Yazdanbakhsh; Phone Number: 773-834-5087; Email: leila.yazdanbakhsh@bsd.uchicago.edu
      • Contact: Phillip LoSavio, MD, MS; Phone Number: 773-702-5189; Email: Phillip.Losavio@bsd.uchicago.edu
      • Principal Investigator: Phillip LoSavio, MD, MS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The subjects will be recruited from the Sleep Surgery Clinic of the Duchossois Center for Advanced Medicine (DCAM) in Hyde Park and Sleep Surgery Clinic of UChicago Medicine - Orland Park and Hinsdale.. We will take advantage of the electronic medical records (EMR) to identify potential candidates using databases (EPIC-based) from the University of Chicago and Ingalls. Participants will be identified by an initial screening of patients scheduled in EPIC for drug induced sleep endoscopy (DISE).

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
HGNS Therapy Participants; Individuals with sleep apnea treated by HGNS therapy.	Device: Hypoglossal Nerve Stimulation (HGNS); Alternative therapy for Obstructive Sleep Apnea
patients with OSA and complete concentric airway collapse on DISE; By standard of care, patients undergoing evaluation for HGNS as an alternative therapy for OSA must undergo drug-induced sleep endoscopy (DISE) to confirm anterior-posterior airway collapse (APC) and rule out complete concentric airway collapse (CCC). Currently, no studies have described the cardiometabolic profiles of patients with OSA and CCC - a population that is both intolerant to PAP and ineligible for HGNS. participants with CCC on DISE will complete an identical set of measures as the APC group. Due to the presence of CCC, these participants will not undergo surgery and will only receive testing once. Data from these subjects will be compared against the baseline (pre-operative) data of the APC group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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	markers of glucose metabolism	at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op
Hemoglobin A1c	markers of glucose metabolism	at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op
Insulin levels	markers of glucose metabolism	at baseline and after HGNS implant, acclimation, and tuning
c-peptide levels	markers of glucose metabolism	at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op
fasting lipid profile (triglycerides)	testing for signs of cardiovascular disease	at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op
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
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
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)	testing for signs of cardiovascular disease	at baseline and after HGNS implant, acclimation, and tuning at 3 month Post-Op
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

Collaborators and Investigators

• Sponsor: University of Chicago
• Investigators: Principal Investigator: Phillip LoSavio, MD, MS, University of Chicago

Study record dates

Study Major Dates

• Study Start (Actual): April 4, 2024
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: February 28, 2024
• First Submitted That Met QC Criteria: March 11, 2024
• First Posted (Actual): March 19, 2024

Study Record Updates

• Last Update Posted (Actual): January 28, 2026
• Last Update Submitted That Met QC Criteria: January 26, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Wake Disorders; Apnea; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Apnea Syndromes; Sleep Apnea, Obstructive
• Other Study ID Numbers: IRB23-1801

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes