The Effect of Mandibular Advancement Devices on Markers of Cardiovascular Health in Mild to Moderate Obstructive Sleep Apnea Patients Who Are Non-Compliant With Continuous Positive Airway Pressure Therapy
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Fasted blood sample- Sex Hormones
研究概览
简要总结
Obstructive sleep apnea (OSA) is a type of disordered breathing defined by the repetitive obstruction of airflow during sleep due to upper airway collapse. Each obstructive event contributes to decreased blood oxygen, or hypoxia. OSA has been associated with various cardiovascular diseases, including hypertension, stroke, heart failure, and coronary artery disease. A factor in this association may be the decrease in blood vessel health and the marked over activation of the sympathetic nervous system that is observed in OSA due to nighttime hypoxia. The sympathetic nervous system is responsible for maintaining heart and blood vessel (cardiovascular) balance. Elevated sympathetic nervous activity (SNA) is a likely cause of hypertension and subsequent cardiovascular disease.
Continuous positive airway pressure (CPAP) therapy is the most accepted treatment for OSA and has been shown to improve high blood pressure and SNA in patients. An alternative therapy for OSA is a type of removable oral appliance known as a mandibular advancement device (MAD). Currently, there is no research directly measuring SNA in OSA patients using MADs. In addition to other cardiovascular markers, the investigators would like to directly assess SNA during a MAD intervention using the gold standard technique of microneurography. The investigators believe this will provide important information for the management of OSA, as levels of SNA are known to respond to both acute and chronic levels of hypoxia. Improved heart and blood vessel markers could further support MAD use, providing an important alternative therapy for those that can not tolerate CPAP.
详细描述
In OSA the obstruction of breathing can be either partial (hypopnea) or complete (apnea), and each obstructive event contributes to decreased blood oxygen, or hypoxia. Sleep disordered breathing and nighttime hypoxia have both been identified as independent risk factors of death. Specifically, OSA is estimated to affect 34% of men and 17% of women and when inadequately treated patients present with daytime sleepiness, depression, workplace accidents and cardiovascular disease.
The severity of OSA is determined by the apnea-hypopnea index (AHI) which is the average number of airway obstructions experienced per hour of sleep. CPAP therapy has been shown to improve high blood pressure, AHI and SNA in patients. However, benefits of CPAP therapy are dose-dependent and are largely affected by patient compliance. Unfortunately, due to various discomforts associated with the use of CPAP therapy, less than fifty percent of patients adhere to long-term therapy.
MADs have increased compliance in comparison to CPAP, and improve some patient's symptoms of sleepiness. Yet, MAD interventions have shown smaller improvements in AHI values when compared to CPAP. However, AHI has been criticized for being an overly simplistic measurement of nocturnal hypoxia. In contrast, SNA is known to respond both acutely and chronically to varying levels of blood oxygen. Therefore, MAD interventions may not produce changes in AHI equal to that of a CPAP intervention; however, they may change levels of SNA and other specific CV markers of blood vessel health. This would further support the use of MADs and provide additional insight into the underlying cardiovascular mechanisms involved in OSA therapy. Understanding and validating additional therapies for OSA is of great importance, due to the significant health consequences of the disease.
Objectives
The proposed investigation aims to determine the following in mild to moderate OSA patients who fail to comply with CPAP therapy:
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Between ages of 18-70
- •Diagnosed with Obstructive Sleep Apnea and prescribed with Mandibular Advancement Device
- •No medical history of cardiovascular, pulmonary, renal diseases
排除标准
- •Any known cardiovascular, respiratory or pulmonary disease
- •Have a history of smoking regularly in past 6 months
- •Pre-existing symptomatic non-respiratory sleep disorder (restless leg syndrome, chronic insomnia)
- •if more than 50% of their observed apneas are due to sleep apnea
结局指标
主要结局
Fasted blood sample- Sex Hormones
时间窗: 3 months
Fasted blood samples (\~30ml) will be analyzed for sex hormones (estrogen, progesterone, testosterone)
Difference in Sympathetic Nerve Activity
时间窗: 3 months
Muscle sympathetic nerve activity. Direct multi-unit postganglionic muscle sympathetic nerve activity (MSNA) will be obtained via microneurography. A sterile Tungsten recording microelectrode (35 mm long, 200 μm in diameter, tapered to a 1- to 5-μm uninsulated tip) will be inserted into a muscle nerve fascicle of a sympathetic nerve bundle, of the peroneal nerve. A reference electrode will also be inserted subcutaneously 1-3 cm from the recording electrode. MSNA will be obtained by manually manipulating the microelectrode until a characteristic bursting pattern is observed A trained researcher will record and analyze to quantify sympathetic activity as: burst frequency (bursts/min), burst incidence (bursts/ 100 heart beats), burst amplitude (normalized to largest resting amplitude), and total activity (burst frequency multiplied by mean normalized burst amplitude)
Difference in Cardiovascular markers - Heart Rate
时间窗: 3 months
All cardiovascular parameters will be acquired using an analog-to-digital converter (Powerlab/16SP ML 880; ADInstruments, Colorado Springs, CO, USA) interfaced with a personal computer. Commercially available software will be used to analyze ventilatory and cardiovascular variables (LabChart V7.1, ADinstruments, Colorado Springs, CO, USA). Throughout all procedures, heart rate will be determined from a standard lead III electrocardiogram (ML 132, ADInstruments, Colorado Springs, CO, USA). Heart Rate will be recorded in beats/ minute
Fasted blood sample- Neurotransmitters
时间窗: 3 months
Fasted blood samples (\~30ml) will be analyzed for sympathetic nervous system neurotransmitters (Norepinephrine, Epinephrine,)
Difference in Cardiovascular markers- Blood Pressure
时间窗: 3 months
All cardiovascular parameters will be acquired using an analog-to-digital converter (Powerlab/16SP ML 880; ADInstruments, Colorado Springs, CO, USA) interfaced with a personal computer. Commercially available software will be used to analyze ventilatory and cardiovascular variables (LabChart V7.1, ADinstruments, Colorado Springs, CO, USA). Throughout all procedures, Blood pressure will be recorded beat-by-beat by finger pulse photoplethysmograph; mmHg.
Endothelial function- time to peak dilation
时间窗: 3 months
Flow Mediated Dilation: This will be assessed in the brachial artery, using an ultrasound system. A sphygmomanometer cuff will be placed and inflated around the forearm to a supra-systolic pressure (250 mmHg) to occlude forearm blood flow for 5 min. After this time period, the cuff will be rapidly deflated (\~1 s). Baseline brachial artery blood flow velocity and diameter will be recorded for 1 minute before cuff inflation, and for 3.5 min beginning 30 s prior to cuff release. (FMD, time to maximal dilation; s)
Endothelial function- Flow mediated dilation
时间窗: 3 months
Flow Mediated Dilation: This will be assessed in the brachial artery, using an ultrasound system. A sphygmomanometer cuff will be placed and inflated around the forearm to a supra-systolic pressure (250 mmHg) to occlude forearm blood flow for 5 min. After this time period, the cuff will be rapidly deflated (\~1 s). Baseline brachial artery blood flow velocity and diameter will be recorded for 1 minute before cuff inflation, and for 3.5 min beginning 30 s prior to cuff release. Percent change in artery diameter will be calculated.
次要结局
未报告次要终点