Endogenous Renin-Angiotensin-Aldosterone System and Glucose Metabolism
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Insulin Secretion
研究概览
简要总结
Aim 1.Test the hypothesis that activation of the endogenous renin-angiotensin-aldosterone system impairs glycemic control via effects on insulin sensitivity and insulin secretion.
Aim 2. Test the hypothesis that activation of the endogenous renin-angiotensin-aldosterone system impairs insulin secretion and insulin sensitivity via an mineralocorticoid-receptor dependent mechanism.
详细描述
In aim 1 subjects are randomized to cross over between an 8 day high salt and 8 day low salt diet and assessments are made.
In aim 2, subjects are randomized to a 2x2 cross over study with an 8 day low salt diet and either eplerenone 50mg or amlodipine 5mg.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ambulatory subjects, 18 to 70 years of age, inclusive
- •For female subjects, the following conditions must be met:
- •postmenopausal status for at least 1 year, or
- •status-post surgical sterilization, or
- •if of childbearing potential, utilization of adequate birth control and willingness to undergo urine beta-hcg testing prior to drug treatment and on every study day.
- •Metabolic Syndrome as defined by the presence of > 3 of the following:
- •Systolic Blood Pressure > 130 mm Hg OR Diastolic Blood Pressure > 85 mm Hg.
- •Glucose Intolerance (Fasting Plasma Glucose ≥ 100 mg/dL)
- •Increased triglyceride level > 150mg/dL (1.7mmol/L)
- •Decreased levels of HDL cholesterol (For males, less than 40 mg/dL; For females, less than 50 mg/dL)
- •Waist circumference (For males, greater than 40 inches; For females, greater than 35 inches)
排除标准
- •type 1 Diabetes
- •Type II Diabetes
- •Impaired renal function
- •Prior allergies to medications used in the study protocol
- •Screening plasma potassium >5.5 mmol/L or sodium <135 mmol/L
- •Cardiovascular disease
- •Use of hormone replacement therapy
- •Breast-feeding
- •Treatment with anticoagulants
- •History of serious neurologic disease
- •History or presence of immunological or hematological disorders
- •Diagnosis of asthma requiring use of inhaled beta agonist
- •Clinically significant gastrointestinal impairment
- •Impaired hepatic function
- •Hematocrit <35%
- •Any underlying or acute disease requiring regular medication which could possibly pose a threat to the subject or make implementation of the protocol or interpretation of the study results difficult, such as arthritis treated with non-steroidal antiinflammatory drugs
- •Treatment with chronic systemic glucocorticoid therapy
- •Treatment with lithium salts
- •History of alcohol or drug abuse
- •Treatment with any investigational drug in the 1 month preceding
- •Mental conditions rendering the subject unable to understand the nature, scope and possible consequences of the study
- •Inability to comply with the protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study
研究组 & 干预措施
Aim1-Low Sodium then High Sodium
Subjects will be provided with a low sodium diet from the Vanderbilt Clinical Research Center that will be controlled for salt content.
Participants will be given low sodium diet (50mEq/d) and Placebo tablets for 8 days and assessments will be made, washout and then cross over to a low sodium diet (50mEq/d) plus Salt tables (150mEq) for 8days and assessments will be made.
干预措施: Low Salt diet plus Placebo tablet (Other)
Aim1-Low Sodium then High Sodium
Subjects will be provided with a low sodium diet from the Vanderbilt Clinical Research Center that will be controlled for salt content.
Participants will be given low sodium diet (50mEq/d) and Placebo tablets for 8 days and assessments will be made, washout and then cross over to a low sodium diet (50mEq/d) plus Salt tables (150mEq) for 8days and assessments will be made.
干预措施: Low Sodium diet plus Salt tablet (Other)
Aim 1-high salt diet then low salt diet
Subjects will be provided with a diet from the Vanderbilt Clinical Research Center that will be controlled for salt content.
Participants will be given low sodium diet (50mEq/d) and Salt tables (150mEq) for 8 days and assessments will be made, washout and then cross over to a low sodium diet (50mEq/d) plus Placebo tablets for 8days and assessments will be made.
干预措施: Low Salt diet plus Placebo tablet (Other)
Aim 1-high salt diet then low salt diet
Subjects will be provided with a diet from the Vanderbilt Clinical Research Center that will be controlled for salt content.
Participants will be given low sodium diet (50mEq/d) and Salt tables (150mEq) for 8 days and assessments will be made, washout and then cross over to a low sodium diet (50mEq/d) plus Placebo tablets for 8days and assessments will be made.
干预措施: Low Sodium diet plus Salt tablet (Other)
Aim2- low salt diet and epleronone then amlodipine
Subjects on a low salt diet will receive Epleronone 50mg for 8 days and assessments will be made, then cross over to a low salt diet with Amlodipine 5mg for 8days and assessments will be made.
干预措施: Low Salt diet plus Placebo tablet (Other)
Aim2- low salt diet and epleronone then amlodipine
Subjects on a low salt diet will receive Epleronone 50mg for 8 days and assessments will be made, then cross over to a low salt diet with Amlodipine 5mg for 8days and assessments will be made.
干预措施: Epleronone (Drug)
Aim2- low salt diet and epleronone then amlodipine
Subjects on a low salt diet will receive Epleronone 50mg for 8 days and assessments will be made, then cross over to a low salt diet with Amlodipine 5mg for 8days and assessments will be made.
干预措施: Amlodipine (Drug)
aim2- low salt diet and amlodipine then epleronone
Subjects on a low salt diet will receive Amlodipine 5mg for 8 days and assessments will be made, then cross over to a low salt diet with Epleronone 50mg for 8days and assessments will be made.
干预措施: Low Salt diet plus Placebo tablet (Other)
aim2- low salt diet and amlodipine then epleronone
Subjects on a low salt diet will receive Amlodipine 5mg for 8 days and assessments will be made, then cross over to a low salt diet with Epleronone 50mg for 8days and assessments will be made.
干预措施: Epleronone (Drug)
aim2- low salt diet and amlodipine then epleronone
Subjects on a low salt diet will receive Amlodipine 5mg for 8 days and assessments will be made, then cross over to a low salt diet with Epleronone 50mg for 8days and assessments will be made.
干预措施: Amlodipine (Drug)
结局指标
主要结局
Insulin Secretion
时间窗: After 8 days of diet or drug
Hyperglycemic clamp- acute insulin response (AIR) during time 0-10 minutes
Insulin Sensitivity
时间窗: after 8 days of diet or medication
Hyperinsulinemic clamp- glucose infusion rate during insulin administration
次要结局
未报告次要终点
研究者
James Matt Luther
M.D., MSCI
Vanderbilt University Medical Center