Pharmacologic Interventions for Cardiovascular Disease in Obstructive Sleep Apnea
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 87
- 试验地点
- 4
- 主要终点
- Change in Muscle Sympathetic Nerve Activity Responses During Hypoxia
研究概览
简要总结
The purpose of this study is to determine if two medicines (allopurinol and losartan) can influence heart and blood vessel health compared to placebo in patients with sleep apnea who are using continuous positive airway pressure (CPAP).
详细描述
The specific aims of this research project are: 1) Determine if treatment with losartan, an angiotensin type I receptor (AT1R) antagonist, or allopurinol, a XO inhibitor, normalize chemoreflex control of sympathetic outflow and ventilation and improve local vascular regulation and stiffness; and 2) Determine if these interventions reduce the severity of sleep disordered breathing and lower diurnal blood pressure.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 21 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females between ages of 21 and 65 years
- •Apnea hypopnea index or respiratory disturbance index greater than or equal to 25 events per hour
- •Subjects eligible for CPAP or BiPAP therapy
- •Hypertension by clinical history/diagnosis (may be controlled with non- exclusionary medications) or average blood pressure > 140/90 mm Hg (using last two measurements in prior 12 months - or 1 prior blood pressure and 1 blood pressure at screening)
排除标准
- •If subject not using CPAP, having AHI > 60 events/hour or oxygen saturation ≤ 65% during sleep
- •Presence of clinical CV disease (coronary artery disease, angina, arrhythmias (subjects with sinus arrhythmias will be reviewed by PI for enrollment), stroke, TIA, cor pulmonale, etc.), heart failure, bruits, or diabetes mellitus by clinical diagnosis/history
- •Presence of pulmonary disease that results in significant hypoxemia (resting SaO2 < 88%)
- •Hypertriglyceridemia (triglycerides >300 mg/dL), diabetes or impaired glucose tolerance (fasting plasma glucose > 125 mg/dL)
- •Patients taking angiotensin converting enzyme inhibitors, angiotensin receptor antagonists, potassium-sparing diuretics (without accompanying loop/thiazide diuretic), allopurinol, oxypurinol, febuxostat, amoxicillin, ampicillin, azathioprine or mercaptopurine.
- •Patients with chronic kidney disease (Serum creatinine >1.5 mg/dL) or history of significant hyperkalemia (Serum potassium > 5.2 mEq/L) with ARB therapy
- •Patients with history of angioedema
- •Patients with bilateral,modified radical or radical mastectomies
- •Patients who have a Serum potassium > 5.0 mEq/L at the screening visit
- •Female patients who are pregnant (determined by urine pregnancy test) or breastfeeding
- •Patients with active MRSA or VRE (vancomycin resistant enterococcus) infection
- •History of adverse reaction to allopurinol,losartan, or zolpidem**
- •Patients who cannot swallow oral capsules
- •Patients who are hospitalized or who have been recently hospitalized (last 2 weeks)
- •Inability to comply with or complete the protocol or other reasons at the discretion of the investigators
研究组 & 干预措施
Losartan
Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic and blood pressure within range.
干预措施: Losartan (Drug)
Allopurinol
Allopurinol 300 mg daily for 6 weeks
干预措施: Allopurinol (Drug)
Placebo
Placebo capsule daily for 6 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Muscle Sympathetic Nerve Activity Responses During Hypoxia
时间窗: baseline and 6 weeks
The primary outcome variable is the change in the individual slope of the MSNA - SaO2 response curve at 6 weeks and baseline between treatment groups.
次要结局
- Change in Minute Ventilation During Hypoxia(baseline and 6 weeks)
- Change in Aortic Pulse Wave Velocity(baseline and 6 weeks)
- Cerebrovascular Conductance(baseline and 6 weeks)
- Forearm Vascular Conductance(baseline and 6 weeks)
- Change in Minute Ventilation at Normoxia(baseline and 6 weeks)
- Aortic Augmentation Index(baseline and 6 weeks)
- Mean Change in PERCENT Vasodilation(baseline and 6 weeks)
- Apnea-Hypopnea Index(baseline and 6 weeks)
- PERCENT Time Spent Below 88 PERCENT Oxygen Saturation(baseline and 6 weeks)
- Change in Mean 24-Hour Blood Pressure (Mean Arterial Pressure)(baseline and 6 weeks)