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

Status

Terminated

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03051165

Enrollment

Registered

2017-02-13

Start date

2016-11-21

Completion date

2017-12-14

Last updated

2018-12-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Obstructive Sleep Apnea

Keywords

Cardiovascular Disease, Pulmonary Medicine, Hypoglossal Nerve Stimulation

Brief summary

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.

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.

Interventions

DEVICEHypoglossal Nerve Stimulation Treatment Withdrawal

After 90 days of hypoglossal nerve stimulation (HGNS), therapy will be discontinued for 30 days before being reactivated.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Masking description

Interpretation of all tests (sleep tests, ambulatory blood pressure monitoring, vascular test and blood tests) will be done by an outcomes assessor who is blinded to whether treatment is active or withheld at the time of testing.

Intervention model description

All participants will undergo the intervention of temporary treatment withdrawal to examine cardiac measurements before treatment, during treatment, and after cessation.

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Change in Peripheral Arterial Tonometry (PAT)	Baseline, Day 105, Day 137	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

Secondary

Measure	Time frame	Description
Change in Peripheral Arterial Stiffness	Baseline, Day 105, Day 137	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.
Change in 24-hour Ambulatory Blood Pressure	Baseline, Day 105, Day 137	To measure 24-hour ambulatory blood pressure, participants wear a watch like device on one arm which records blood pressure throughout the day.
Change in C-reactive Protein	Baseline, Day 105, Day 137	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.
Change in Flow Mediated Dilation	Baseline, Day 105, Day 137	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.
Change in Heat Shock Protein 70 (HSP70)	Baseline, Day 105, Day 137	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.
Change in High Sensitivity Cardiac Troponin (HS-troponin)	Baseline, Day 105, Day 137	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.
Change in Soluble Urokinase-type Plasminogen Activator Receptor (suPAR)	Baseline, Day 105, Day 137	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.
Change in Fibrin Degradation Products	Baseline, Day 105, Day 137	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.

Countries

United States

Participant flow

Recruitment details

Participants were recruited from the Emory Sleep Center in Atlanta, Georgia. Enrollment began on 11/21/2016 and the study was terminated early on 12/14/2017.

Participants by arm

Arm	Count
Hypoglossal Nerve Stimulation Treatment Withdrawal Recipients of hypoglossal nerve stimulation (HGNS) who consented to have temporary withdrawal of treatment.	13
Total	13

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Early termination of study	12
Overall Study	Withdrawal by Subject	1

Baseline characteristics

Characteristic	Hypoglossal Nerve Stimulation Treatment Withdrawal
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	11 Participants
Age, Categorical Between 18 and 65 years	2 Participants
Age, Continuous	67 years STANDARD_DEVIATION 10.5
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	2 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	11 Participants
Region of Enrollment United States	13 Participants
Sex: Female, Male Female	8 Participants
Sex: Female, Male Male	5 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 13
other Total, other adverse events	0 / 13
serious Total, serious adverse events	0 / 13

Outcome results

Primary

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