Vanderbilt University Medical Center
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Contrast Enhanced-Ultrasonography (CEU)
研究概览
简要总结
The purpose of this study is to better understand the contribution of sympathetic vasoconstriction to impaired insulin-mediated vasodilation and subsequently insulin-mediated glucose uptake. The investigators will test the hypothesis that removal of sympathetic vasoconstriction can result in improvement in insulin-mediated vasodilation and subsequently sensitivity to insulin-mediated glucose uptake.
详细描述
Several studies have shown that obese subjects have impaired Nitric Oxide (NO)-mediated dilation; and those who develop insulin resistance tend to be more obese, have higher insulin levels and greater sympathetic activity. Furthermore, we have made the novel observation that autonomic blockade improves glucose utilization in obese subjects with insulin resistance, providing a causal relation between sympathetic activation and insulin resistance. The autonomic blockade also improved NO-mediated dilation in obese subjects, which may improve glucose uptake by promoting glucose delivery.
The investigators will enroll obese insulin-resistant subjects and in parallel experiments two comparator groups: obese insulin sensitive subjects, and healthy lean control subjects. We will assess the effects of insulin (hyperinsulinemic euglycemic clamp) on microvascular recruitment, and forearm glucose uptake on two separate occasions randomly assigned and at least one month apart, during an intrabrachial infusion of the alpha-adrenergic blocker phentolamine (blocked day) or saline control (Control day).
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
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Males and females of all races between 18 and 60 years of age.
- •Obesity defined as body mass index between 30-40 kg/m2
- •Insulin resistance defined as homeostasis model assessment 2 insulin resistance (HOMA2-IR) score >1.6 (never diagnosed or treated type 2 diabetic), or being a well-controlled type 2 diabetic on metformin only.
- •Able and willing to provide informed consent
排除标准
- •Pregnancy or breastfeeding
- •Current smokers or history of heavy smoking (>2 packs/day)
- •History of alcohol or drug abuse
- •Morbid obesity (BMI > 40 kg/m2)
- •Previous allergic reaction to study medications
- •Evidence of type I diabetes.
- •Cardiovascular disease other than hypertension such as myocardial infarction within 6 months prior to enrollment, presence of angina pectoris, significant arrhythmia, congestive heart failure (LV hypertrophy acceptable), deep vein thrombosis, pulmonary embolism, second or third-degree heart block, mitral valve stenosis, aortic stenosis, or hypertrophic cardiomyopathy
- •History of serious cerebrovascular disease such as cerebral hemorrhage, stroke, or transient ischemic attack
- •History or presence of immunological or hematological disorders
- •Impaired hepatic function [aspartate amino transaminase (AST) and/or alanine amino transaminase (ALT) > 2.0 x upper limit of normal range]
- •Impaired renal function (serum creatinine >1.5 mg/dl)
- •Moderate to severe anemia (hemoglobin <11 g/dl)
- •Treatment with serotonin-norepinephrine reuptake inhibitors (SNRIs) or norepinephrine transporter (NET) inhibitors
- •Treatment with phosphodiesterase 5 inhibitors
- •Treatment with anticoagulants
- •Treatment with chronic systemic glucocorticoid therapy (more than 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
- •Other factors which in the investigator's opinion would prevent the subject from completing the protocol (i.e., clinically significant abnormalities on clinical, mental examination or laboratory testing or inability to comply with protocol)
研究组 & 干预措施
Intact Day
Saline
干预措施: Saline (Other)
Blocked Day
Phentolamine
干预措施: Phentolamine (Drug)
Vasodilator Comparison
Sodium Nitroprusside
干预措施: Sodium Nitroprusside (Drug)
结局指标
主要结局
Contrast Enhanced-Ultrasonography (CEU)
时间窗: Before clamp and 15 minutes after clamp
The Primary Outcome will be the change in CEU induced by insulin during hyperinsulinemic clamp compared to baseline. To test the null hypothesis that insulin will not produce any changes in microvascular blood volume using CEU in response to α-adrenergic blockade (phentolamine) in the isolated forearm model.
次要结局
未报告次要终点
研究者
Italo Biaggioni
Professor Medicine and Pharmacology
Vanderbilt University Medical Center