Effect of Upper Airway Stimulation on Vascular Function in Obstructive Sleep Apnea

This study will evaluate the effect of hypoglossal nerve stimulation (HGNS) on different measures of cardiovascular function in patients with obstructive sleep apnea (OSA). People with OSA who have undergone implantation of the hypoglossal nerve stimulator at the study site will be told about the study at their 2-week post-operative appointment. Those who decide to participate will have blood drawn and vascular function measurements taken before HGNS activation, during treatment, and after a temporary treatment withdrawal period. Following the 30-day period of treatment withdrawal, the HGNS therapy will be reactivated.

Study Overview

• Status: Terminated
• Conditions: Obstructive Sleep Apnea
• Intervention / Treatment: Device: Hypoglossal Nerve Stimulation Treatment Withdrawal

Detailed Description

Obstructive sleep apnea (OSA), the repetitive collapse of the upper airway during sleep, represents a growing individual and public health concern. This disease negatively impacts patients' sleep quality and daytime function, including an increased risk of motor vehicle accidents. Several large, longitudinal cohorts have consistently demonstrated deleterious effects of OSA on cardiovascular health, including elevated rates of incident hypertension, myocardial infarction and cerebrovascular accidents. The link between OSA and cardiovascular consequences can be largely explained by autonomic imbalance during repeated episodes of nocturnal airway obstruction. Compared to those without OSA, people with OSA have increased sympathetic activity when awake, with further elevation of both sympathetic activity and blood pressure during sleep. Multiple physiologic mechanisms are responsible for these autonomic changes during obstructive episodes including the interaction of baroreceptors, chemoreceptors and respiratory afferent receptors.

Positive airway pressure (PAP) serves as a pneumatic stent for the airway, maintaining airway patency and normoxia. PAP therapy has demonstrated consistent, meaningful reductions in sympathetic overactivity during wake and sleep. Although PAP therapy is highly efficacious, fewer than 50% of patients are adequately treated due to adherence difficulty. In 2014, the Federal Drug Administration approved hypoglossal nerve stimulation (HGNS) for the treatment of patients with moderate-severe OSA who are unable to adequately use PAP. This therapy has demonstrated stable, marked improvement in key polysomnography indices, sleepiness measures and functional outcomes, however, no study has examined cardiovascular endpoints of HGNS therapy in OSA patients.

The aim of this study is to evaluate the effect of HGNS therapy on autonomic and vascular function before, during and after treatment for OSA with HGNS. People who have undergone implantation of the hypoglossal nerve stimulator at the study site will be told about the study at their 2-week post-operative appointment. Those who decide to participate in the study will have blood drawn and vascular function measurements taken before the HGNS device is activated, during treatment, and after a temporary treatment withdrawal period. The researchers hypothesize that all aforementioned measurements will be significantly improved following HGNS therapy and return to baseline values following a therapy withdrawal period.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Emory Sleep Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• English-speaking
• Able to give informed consent

• Have undergone implantation of hypoglossal nerve stimulator (HGNS) by the principal investigator of this study. HGNS inclusion criteria per FDA are as follows:

  • Apnea-hypopnea index (AHI) of 20 or more from recent sleep test
  • Unable to use positive airway pressure therapy
  • Body Mass Index (BMI) < 32 kg/m2
  • Without circumferential collapse on drug-induced sedated endoscopy

Exclusion Criteria:

• Active smokers
• Unstable and untreated coronary or peripheral artery disease
• Use of alpha-blockers
• Severe and inadequately controlled arterial hypertension

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Hypoglossal Nerve Stimulation Treatment Withdrawal; Recipients of hypoglossal nerve stimulation (HGNS) who agree to participate in the study will have additional tests done to monitor cardiovascular responses to HGNS therapy and the temporary withdrawal of treatment.	Device: Hypoglossal Nerve Stimulation Treatment Withdrawal; After 90 days of hypoglossal nerve stimulation (HGNS), therapy will be discontinued for 30 days before being reactivated.; Other Names: HGNS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Peripheral Arterial Tonometry (PAT)	Peripheral arterial tonometry (PAT) is a method for measuring endothelial dysfunction in a non-invasive way. Blood flow is measured in the fingertips following compression with an inflatable cuff on the upper arm. Participants will lay on their backs with a probe placed on the finger of each hand. The probes are attached to a computer that records finger blood flow. The finger probes will continuously record the blood flow in the fingertips for 10 minutes	Baseline, Day 105, Day 137

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Flow Mediated Dilation	Flow mediated dilation is a method to assess endothelial function using an ultrasound device to take measurements of the artery at the elbow. Blood vessel diameter is measured before and after blood pressure cuff release and flow mediated dilation is the percent of change between the baseline and post cuff release measurements. A lower measurement of dilation corresponds with an increased risk for cardiovascular events.	Baseline, Day 105, Day 137
Change in Peripheral Arterial Stiffness	Recordings of blood flow through the artery in the wrist will be obtained with application of a probe applied to the skin. Participants will be seated or lying down for this test which takes approximately 10 minutes. Increased arterial stiffness is associated with an increased risk of cardiovascular events.	Baseline, Day 105, Day 137
Change in 24-hour Ambulatory Blood Pressure	To measure 24-hour ambulatory blood pressure, participants wear a watch like device on one arm which records blood pressure throughout the day.	Baseline, Day 105, Day 137
Change in C-reactive Protein	To assess changes in the serum biomarker profile, blood will be collected from participants to be stored for future analyses of a variety of biochemical factors related to cardiovascular function. C-reactive protein is produced by the liver and increased concentrations are found when inflammation is present in the body.	Baseline, Day 105, Day 137
Change in Fibrin Degradation Products	To assess changes in the serum biomarker profile, blood will be collected from participants to be stored for future analyses of a variety of biochemical factors related to cardiovascular function. Fibrin degradation products are produced by of clot degeneration. Plasma fibrin degradation products increase following clot formation.	Baseline, Day 105, Day 137
Change in Heat Shock Protein 70 (HSP70)	To assess changes in the serum biomarker profile, blood will be collected from participants to be stored for future analyses of a variety of biochemical factors related to cardiovascular function. Heat shock protein 70 (HSP70) is a stress protein. Heat shock proteins increase in response to stress conditions such as inflammation and infection.	Baseline, Day 105, Day 137
Change in High Sensitivity Cardiac Troponin (HS-troponin)	To assess changes in the serum biomarker profile, blood will be collected from participants to be stored for future analyses of a variety of biochemical factors related to cardiovascular function. Elevated high sensitivity cardiac troponin (HS-troponin) indicates injury to the heart.	Baseline, Day 105, Day 137
Change in Soluble Urokinase-type Plasminogen Activator Receptor (suPAR)	To assess changes in the serum biomarker profile, blood will be collected from participants to be stored for future analyses of a variety of biochemical factors related to cardiovascular function. Soluble urokinase-type plasminogen activator receptor (suPAR) is a marker for disease status by indicating the degree of activation of the immune system. Higher concentrations indicate inflammation and are associated with an increased risk of mortality.	Baseline, Day 105, Day 137

Collaborators and Investigators

• Sponsor: Emory University
• Investigators: Principal Investigator: Raj Dedhia, MD, Emory University

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2016
• Primary Completion (Actual): December 14, 2017
• Study Completion (Actual): December 14, 2017

Study Registration Dates

• First Submitted: February 9, 2017
• First Submitted That Met QC Criteria: February 9, 2017
• First Posted (Actual): February 13, 2017

Study Record Updates

• Last Update Posted (Actual): December 11, 2018
• Last Update Submitted That Met QC Criteria: November 15, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Cardiovascular Disease; Pulmonary Medicine; Hypoglossal Nerve Stimulation
• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Apnea
• Other Study ID Numbers: IRB00088693

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