Clinical trial NCT03051165: Effect of Upper Airway Stimulation on Vascular Function in Obstructive Sleep Apnea
Official title: Effect of Upper Airway Stimulation on Vascular Function in Obstructive Sleep Apnea
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Obstructive Sleep Apnea
Keywords: Cardiovascular Disease
Pulmonary Medicine
Hypoglossal Nerve Stimulation
Lead sponsor: Emory University
Sponsor class: OTHER
First posted: 2017-02-13
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All participants will undergo the intervention of temporary treatment withdrawal to examine cardiac measurements before treatment, during treatment, and after cessation.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Peripheral Arterial Tonometry (PAT)
timeFrame: Baseline, Day 105, Day 137
Secondary outcomes:
measure: Change in Flow Mediated Dilation
timeFrame: Baseline, Day 105, Day 137
measure: Change in Peripheral Arterial Stiffness
timeFrame: Baseline, Day 105, Day 137
measure: Change in 24-hour Ambulatory Blood Pressure
timeFrame: Baseline, Day 105, Day 137
measure: Change in C-reactive Protein
timeFrame: Baseline, Day 105, Day 137
measure: Change in Fibrin Degradation Products
timeFrame: Baseline, Day 105, Day 137
measure: Change in Heat Shock Protein 70 (HSP70)
timeFrame: Baseline, Day 105, Day 137
measure: Change in High Sensitivity Cardiac Troponin (HS-troponin)
timeFrame: Baseline, Day 105, Day 137
measure: Change in Soluble Urokinase-type Plasminogen Activator Receptor (suPAR)
timeFrame: Baseline, Day 105, Day 137
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory Sleep Center
state: Georgia
Study officials:
affiliation: Emory University
name: Raj Dedhia, MD
role: PRINCIPAL_INVESTIGATOR
References: