Angiotensin-(1-7) and Energy Expenditure in Human Obesity
试验速览
- 阶段
- 早期 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Resting energy expenditure
研究概览
简要总结
The objective of this study is to better define the role of the hormone angiotensin-(1-7) in energy balance. We will test the overall hypothesis that angiotensin-(1-7) increases resting energy expenditure and promotes markers of heat production (thermogenesis) in white adipose tissue in human obesity.
详细描述
Angiotensin-(1-7) is a beneficial hormone of the renin-angiotensin system known to produce positive cardiovascular and metabolic effects in animal models. In this study, the investigators will determine if angiotensin-(1-7) can increase resting energy expenditure and promote white adipose tissue heat production (thermogenesis) in obese human subjects. The investigators will perform a randomized, double-blind, two-arm parallel group study to determine effects of acute intravenous angiotensin-(1-7) versus saline infusion on resting energy expenditure measured by indirect calorimetry in obese human participants. In addition, blood pressure and heart rate will be measured and blood samples obtained to measure for changes in circulating renin-angiotensin system and metabolic hormones. Abdominal subcutaneous white adipose biopsies will also be obtained from obese human participants during acute angiotensin-(1-7) versus saline infusions to examine for changes in gene expression for markers of thermogenesis. The findings from these studies will advance understanding of hormonal mechanisms involved in the etiology of obesity, and provide new insight into the potential for targeting angiotensin-(1-7) to improve energy balance in human obesity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women of all races
- •Capable of giving informed consent
- •Age 18-60 years
- •Body mass index (BMI) between 30-40 kg/m2
- •Satisfactory history and physical exam
排除标准
- •Age ≤ 17 or ≥ 61 years
- •Pregnant, nursing, or postmenopausal women
- •Decisional impairment
- •Prisoners
- •Alcohol or drug abuse
- •Current smokers
- •Highly trained athletes
- •Claustrophobia
- •Subjects with >5% weight change in the past 3 months
- •Evidence of type I or type II diabetes (fasting glucose > 126 mg/dL or use of anti-diabetic medications)
- •History of serious cardiovascular disease other than hypertension (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 or alanine aminotransferase levels >2 times upper limit of normal range)
- •Impaired renal function (serum creatinine >2.0 mg/dl)
- •Treatment with anticoagulants (e.g. warfarin)
- •Treatment with chronic systemic glucocorticoid therapy (>7 consecutive days in 1 month)
- •Treatment with medications influencing energy expenditure (e.g. psychostimulants)
- •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)
Subjects will receive intravenous infusion of three ascending doses of angiotensin-(1-7). The doses are: 2, 4, and 8 ng/kg/min. Each dose will be maintained for 10 minutes, with the highest dose maintained for an additional 90 minutes. The total infusion period is 120 minutes.
干预措施: Angiotensin-(1-7) (Drug)
Placebo
Subjects will receive intravenous infusion of saline that is matched in volume to the angiotensin-(1-7). The total infusion period is 120 minutes.
干预措施: Saline (Drug)
结局指标
主要结局
Resting energy expenditure
时间窗: 120 minutes
Change in resting energy expenditure measured by indirect calorimetry at baseline and at end of angiotensin-(1-7) versus saline infusion.
Uncoupling protein 1
时间窗: 120 minutes
White adipose tissue biopsies will be taken at end of angiotensin-(1-7) versus saline infusion to assess gene expression of the heat producing (thermogenic) marker uncoupling protein 1.
次要结局
- Heart rate(120 minutes)
- Blood pressure(120 minutes)
研究者
Amy Arnold
Associate Professor
Milton S. Hershey Medical Center