Role of Mineralocorticoid Receptor in Diabetic Cardiovascular Disease
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 69
- 试验地点
- 1
- 主要终点
- Change in Coronary Flow Reserve From Baseline to 6 Months
研究概览
简要总结
Aldosterone is a significant mediator of cardiovascular injury associated with heart failure and the cardiovascular benefits of mineralocorticoid receptor blockade are additive to those of angiotensin converting enzyme inhibitors or angiotensin II (ANGII) receptor blockers. This study will test the hypothesis that mineralocorticoid receptor (MR) antagonists exert beneficial cardiovascular effects, specifically by decreasing vascular injury and improving vascular function. A randomized, double-blind study will be conducted, in which participants with Type 2 Diabetes Mellitus will undergo a series of assessments to test heart, blood vessel, and kidney function at baseline, and after 2 and 6 months of treatment with one of the following drugs:
- spironolactone
- hydrochlorothiazide (HCTZ) plus potassium
- placebo
In the event of insufficient funds, randomization to the placebo arm will be stopped and primary assessment of outcomes will occur at baseline and after 6 months of treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 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
- •age 18-70 years
- •type 2 diabetes mellitus
- •with or without hypertension
排除标准
- •ischemic changes on resting electrocardiogram,
- •clinical evidence of heart disease (angina, heart failure, unstable angina),cerebrovascular or peripheral vascular disease,
- •significant cardiac arrhythmias,
- •aortic stenosis,
- •2nd or 3rd degree atrio-ventricular block, sinus node disease, or symptomatic bradycardia,
- •bronchospastic lung disease with active wheezing,
- •known hypersensitivity to adenosine,
- •hemoglobin A1C (HbA1c) > 8.5%, *
- •gout (If not already taking HCTZ),
- •the use of Rosiglitazone,**
- •estimated glomerular filtration rate (eGFR) < 60 ml/min,
- •serum potassium > 5.0 mmol/L,
- •use of potassium-sparing diuretics,**
- •current smoker,*
- •pregnancy,
- •renal disease not related to diabetes mellitus,
- •uncontrolled hypertension, systolic blood pressure (BP) >160 mm Hg and diastolic BP >100 mm Hg,*
- •use of cyclic hormone replacement therapy
- •past intolerance of angiotensin-converting enzyme (ACE) inhibitor therapy
- •other major medical illnesses. Participants with evidence of a previous myocardial infarction on the first adenosine-stimulated positron emission tomography (PET) study will be withdrawn from the study.
- •Screening systolic blood pressure < 105 mm Hg off of anti-hypertensive medications
- •Participants can enroll in study and proceed with in-patient evaluations if during the run-in period adjustments of medications, diet and habits lead to improved glucose control [equivalent to HbA1c <8.5%, controlled hypertension and cessation of smoking.
- •Participants who are currently taking these medications will not qualify for a screening visit. If medications were recently stopped by the participant's physician, he or she may be screened but the baseline assessment protocol must occur 3 months after stopping.
研究组 & 干预措施
Spironolactone (mineralocorticoid receptor [MR] blockade)
干预措施: Spironolactone (Drug)
Hydrochlorothiazide + potassium
干预措施: Hydrochlorothiazide + potassium (Drug)
Placebo capsule
干预措施: Placebo (Other)
结局指标
主要结局
Change in Coronary Flow Reserve From Baseline to 6 Months
时间窗: Baseline and six months
Coronary flow reserve (CFR), or myocardial perfusion reserve, was assessed via cardiac positron emission tomography (PET). CFR is the ratio of adenosine-stimulated blood flow through myocardium to resting blood flow through myocardium. An improvement in coronary flow reserve is beneficial.
次要结局
- Change in Renal Plasma Flow(Baseline and six months)
- Change in Mitral Annulus Velocities on Tissue Doppler (Delta E/e' Ratio), a Measure of Diastolic Function(Baseline and six months)
- Mitral Annulus Velocities on Tissue Doppler (Delta E/e' Ratio), a Measure of Diastolic Function (With Angiotensin II)(Baseline and six months)
研究者
Gail Kurr Adler
Associate Professor of Medicine
Brigham and Women's Hospital