Cardiovascular Effects of Angiotensin-(1-7) in Obesity Hypertension
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- Change in Muscle Sympathetic Nerve Burst Rate
研究概览
简要总结
Obesity is a global health concern that is associated with high blood pressure and an increased risk for developing cardiovascular disease. The purpose of this study is to find out if the investigational drug angiotensin-(1-7) can improve cardiovascular health in people with obesity and high blood pressure.
详细描述
A randomized, double blind, placebo controlled, crossover study will be conducted to determine if acute intravenous angiotensin-(1-7) infusion reduces cardiovascular sympathetic tone and blood pressure and improves the function of blood vessels in participants with obesity hypertension. This is an outpatient study that requires a screening visit, and if eligible, two study visits separated by at least one week in the Clinical Research Center within the Penn State Milton S. Hershey Medical Center. The study visits will include intravenous infusion of angiotensin-(1-7) or saline for approximately two hours, starting with increasing doses and holding at a steady-state dose. Endothelial function will be measured and blood samples collected at baseline and at the end of infusion. Blood pressure, heart rate, and muscle sympathetic nerve activity (via microneurography) will be measured continuously throughout the study. Each study visit will last approximately 4 hours.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women of all races
- •Age 18 to 65 years
- •Body mass index (BMI) between 30-45 kg/m2
- •Pre-hypertension (defined as two or more seated blood pressure readings >120/80 mmHg) or hypertension (defined as two or more seated blood pressure readings >130/80 mmHg or use of antihypertensive medications)
- •Capable of giving informed consent
- •Fluent in written and spoken English
- •Satisfactory history and physical exam
排除标准
- •Age ≤ 17 or ≥ 66 years
- •Taking more than two antihypertensive medications
- •Secondary causes of hypertension (e.g., pheochromocytoma, primary aldosteronism, aortic coarctation, adrenal disease)
- •Pregnant or nursing women
- •Women taking hormone replacement therapy within 6 months
- •Decisional impairment
- •Prisoners
- •Alcohol or drug abuse
- •Current smokers
- •Highly trained athletes
- •Subjects with >5% weight change in the past 3 months
- •BMI > 45 kg/m2
- •Evidence of type I or type II diabetes (fasting glucose > 126 mg/dL or use of anti-diabetic medications)
- •History of serious cardiovascular disease (e.g. myocardial infarction within 6 months, symptomatic coronary artery disease, presence of angina pectoris, significant arrhythmia, congestive heart failure, deep vein thrombosis, pulmonary embolism, second or third degree heart block, mitral valve stenosis, aortic stenosis, hypertrophic cardiomyopathy) or cerebrovascular disease (e.g. cerebral hemorrhage, stroke, transient Ischemic attack)
- •History or presence of immunological or hematological disorders
- •Impaired hepatic function [aspartate aminotransferase (AST) or alanine transaminase (ALT) levels >2 times upper limit of normal range]
- •Impaired renal function (serum creatinine >2.0 mg/dl)
- •Treatment with drugs increasing sympathetic activity [e.g., serotonin-norepinephrine reuptake inhibitors (SNRIs) or norepinephrine transporter (NET) inhibitors, stimulants]
- •Treatment with phosphodiesterase-5 inhibitors
- •Treatment with anticoagulants (e.g. warfarin)
- •Treatment with chronic systemic glucocorticoid therapy (>7 consecutive days in 1 month)
- •Treatment with any investigational drug in the 1-month preceding the study
- •Inability to give, or withdraw, informed consent
研究组 & 干预措施
Angiotensin-(1-7)
Participants will receive intravenous angiotensin-(1-7) at one study visit for a total of 120 minutes. Angiotensin-(1-7) will be given in escalating doses of 2 ng/kg/min, 4 ng/kg/min, and 8 ng/kg/min. Each of these doses will be infused for 10 minutes. Following this 30 minute dose escalation period, angiotensin-(1-7) will be given at 8 ng/kg/min for an additional 90 minutes. Infusion rates will be calculated for each patient based on body mass.
干预措施: Angiotensin-(1-7) (Drug)
Saline
Participants receive intravenous saline at one study visit for a total of 120 minutes. The volume of saline will match the volume of angiotensin-(1-7) infused. Infusion rates will be calculated for each patient based on body mass.
干预措施: Saline (Drug)
结局指标
主要结局
Change in Muscle Sympathetic Nerve Burst Rate
时间窗: 120 minutes
Muscle sympathetic nerve burst rate will be measured continuously using peroneal nerve microneurography during angiotensin-(1-7) versus saline infusion.
Change in Brachial Artery Diameter
时间窗: 120 minutes
A blood pressure cuff will be inflated to a suprasystolic pressure for 5 minutes then deflated. Brachial artery diameter will be measured continuously before, during, and after cuff inflation using duplex ultrasound at baseline and at the end of angiotensin-(1-7) versus saline infusion.
次要结局
- Change in Muscle Sympathetic Nerve Total Activity(120 minutes)
- Change in Systolic Blood Pressure(120 minutes)
- Change in Diastolic Blood Pressure(120 minutes)
- Change in Heart Rate(120 minutes)
- Change in Muscle Sympathetic Nerve Burst Incidence(120 minutes)
- Change in Muscle Sympathetic Nerve Amplitude(120 minutes)
- Change in Plasma Catecholamines(120 minutes)
研究者
Amy Arnold
Associate Professor
Milton S. Hershey Medical Center