The Role of Aldosterone on Sympathetic Nerve Activity and Insulin Sensitivity
试验速览
- 阶段
- 4 期
- 状态
- 撤回
- 发起方
- 试验地点
- 1
- 主要终点
- Increase in muscle sympathetic nerve activity during hyperinsulinemic euglycemic clamp
研究概览
简要总结
Patients with high aldosterone hormone have higher blood glucose than normal people. This study is being done to understand how aldosterone hormone affects the nerve activity that controls blood flow in the muscles and blood glucose. The information may be helpful in selecting blood pressure medications which can improve not only blood pressure but also improve blood sugar.
详细描述
Patients with primary aldosteronism are known to have impaired insulin sensitivity, which is improved after removal of aldosterone-producing adenoma. In patients with essential hypertension, plasma aldosterone levels have been also shown to positively correlate with indices of insulin resistance.
Mechanism underlying aldosterone-induced insulin resistance is unknown. Aldosterone has been shown to interfere with insulin signaling the vascular cells by increasing production of reactive oxygen species via activation of NADPH oxidase, resulting in decreased availability of nitric oxide (NO), the key mediator for insulin-mediated vasodilation. Treatment with mineralocorticoid receptor antagonists has been shown to improve insulin sensitivity in mice with obesity and metabolic syndrome. Aldosterone has also been shown to increase resting sympathetic vasoconstrictor activity to the peripheral circulation. However, effects of aldosterone and mineralocorticoid receptor antagonists on insulin-mediated skeletal muscle vasodilation, sympathetic activation, and vascular oxidative stress have not been assessed in humans.
The investigators will collect venous endothelial cells, and measure skeletal muscle microvascular perfusion using Octafluoropropane microbubble contrast agents, and measure sympathetic nerve activity in normotensive controls (NT), stage 1 essential hypertensive subjects (ET), and patients with primary aldosteronism (PA) during hyperinsulinemic euglycemic clamp.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Normotensive controls
- •Stage I (140-159/90-99 mmHg) untreated subjects with essential hypertension
- •Patients with PA and stage I (140-159/90-99 mmHg) hypertension
排除标准
- •Congestive heart failure or coronary artery disease
- •Blood pressure averaging > 159/99 mmHg
- •Serum creatinine > 1.5 mg/dL
- •Diabetes mellitus or other systemic illness
- •Left ventricular hypertrophy by echocardiography or ECG
- •Hypersensitivity to spironolactone, chlorthalidone, amlodipine, human recombinant insulin or Definity
- •Any history of substance abuse (other than tobacco)
- •History of gouty arthritis
- •Patients with right-to-left, bi-directional, or transient right-to-left cardiac shunts
- •Hypersensitivity to perflutren, blood, blood products or albumin
研究组 & 干预措施
Hyperinsulinemic euglycemic clamp
We will perform following procedures:
DEFINITY® infusion Flow mediated vasodilation Endothelial cell collection Microvascular perfusion assessment using Definity Microneurography
干预措施: DEFINITY® infusion (Drug)
Hyperinsulinemic euglycemic clamp
We will perform following procedures:
DEFINITY® infusion Flow mediated vasodilation Endothelial cell collection Microvascular perfusion assessment using Definity Microneurography
干预措施: Human Recombinant Regular Insulin infusion (Drug)
Hyperinsulinemic euglycemic clamp
We will perform following procedures:
DEFINITY® infusion Flow mediated vasodilation Endothelial cell collection Microvascular perfusion assessment using Definity Microneurography
干预措施: Dextrose infusion (Drug)
Hyperinsulinemic euglycemic clamp
We will perform following procedures:
DEFINITY® infusion Flow mediated vasodilation Endothelial cell collection Microvascular perfusion assessment using Definity Microneurography
干预措施: Flow mediated vasodilation (Procedure)
Hyperinsulinemic euglycemic clamp
We will perform following procedures:
DEFINITY® infusion Flow mediated vasodilation Endothelial cell collection Microvascular perfusion assessment using Definity Microneurography
干预措施: Endothelial cell collection (Procedure)
Hyperinsulinemic euglycemic clamp
We will perform following procedures:
DEFINITY® infusion Flow mediated vasodilation Endothelial cell collection Microvascular perfusion assessment using Definity Microneurography
干预措施: Microvascular perfusion assessment using Definity (Procedure)
Hyperinsulinemic euglycemic clamp
We will perform following procedures:
DEFINITY® infusion Flow mediated vasodilation Endothelial cell collection Microvascular perfusion assessment using Definity Microneurography
干预措施: Microneurography (Procedure)
Initial Saline Infusion
We will perform the following procedures:
DEFINITY® infusion Human Recombinant Regular Insulin infusion Dextrose infusion Flow mediated vasodilation Endothelial cell collection Microvascular perfusion assessment using Definity Microneurography
干预措施: DEFINITY® infusion (Drug)
Initial Saline Infusion
We will perform the following procedures:
DEFINITY® infusion Human Recombinant Regular Insulin infusion Dextrose infusion Flow mediated vasodilation Endothelial cell collection Microvascular perfusion assessment using Definity Microneurography
干预措施: Flow mediated vasodilation (Procedure)
Initial Saline Infusion
We will perform the following procedures:
DEFINITY® infusion Human Recombinant Regular Insulin infusion Dextrose infusion Flow mediated vasodilation Endothelial cell collection Microvascular perfusion assessment using Definity Microneurography
干预措施: Endothelial cell collection (Procedure)
Initial Saline Infusion
We will perform the following procedures:
DEFINITY® infusion Human Recombinant Regular Insulin infusion Dextrose infusion Flow mediated vasodilation Endothelial cell collection Microvascular perfusion assessment using Definity Microneurography
干预措施: Microvascular perfusion assessment using Definity (Procedure)
Initial Saline Infusion
We will perform the following procedures:
DEFINITY® infusion Human Recombinant Regular Insulin infusion Dextrose infusion Flow mediated vasodilation Endothelial cell collection Microvascular perfusion assessment using Definity Microneurography
干预措施: Microneurography (Procedure)
结局指标
主要结局
Increase in muscle sympathetic nerve activity during hyperinsulinemic euglycemic clamp
时间窗: 1 day
次要结局
- Change in microvascular blood flow during saline infusion.(1 day)
- Change in endothelial cell protein expression after saline infusion(1 day)
- Change in endothelial cell protein expression after hyperinsulinemic euglycemic clamp(1 day)
- Increase in muscle sympathetic nerve activity during saline infusion(1 day)
- Change in microvascular blood flow during hyperinsulinemic euglycemic clamp.(1 day)
研究者
Wanpen Vongpatanasin
PROFESSOR
University of Texas Southwestern Medical Center