Assessment of Renin Inhibition on Insulin Sensitivity, Diastolic Function and Aortic Compliance
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Change in Insulin Sensitivity by HOMA at 12 Weeks
研究概览
简要总结
This study is an investigation of the effect of commonly prescribed anti-hypertensive agents on insulin sensitivity, diastolic function and aortic compliance. The aims of the study are as follows:
Specific Aim 1: To determine in insulin resistant, hypertensive subjects if renin inhibition for 12 weeks modifies glucose homeostasis and insulin sensitivity.
To accomplish this specific aim, we will use three approaches: a fasting HOMA Index; and a three hour glucose tolerance test. Only hypertensive subjects with insulin resistance, as assessed by HOMA index will be enrolled in the study. Insulin resistance will be assessed basally and after twelve weeks of treatment with either a calcium channel blocker with placebo, or calcium channel blocker with a renin inhibitor, or a calcium channel blocker with a renin inhibitor and an angiotensin receptor antagonist.
Specific Aim 2: To determine in insulin resistant, hypertensive subjects if renin inhibition for 12 weeks modifies diastolic function and aortic compliance response to dietary sodium intake.
The same protocol and subjects will be used as defined in Specific Aim 1. Myocardial relaxation velocity (tissue Doppler imaging at the mitral annulus) and aortic compliance (characteristic aortic impedance) will be measured at baseline and then after acute and chronic renin inhibition:
- Acute effect of renin inhibition: Hemodynamic measurements will be obtained on both high and low dietary sodium intake conditions (~1 week each) before and after a single dose of a renin inhibitor.
- Chronic effect of renin inhibition: Hemodynamic measurements will be obtained at baseline and after 12 weeks of each of the three drug treatment arms above.
The study lasts 12 weeks and plans to study 45 hypertensive adults over the next two years.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- 否
入选标准
- •Men and women, 18-70 years old
- •BMI =/< 35
- •BP: BP > 145/95 on no BP medication or on 3 or less BP medications
- •HOMA =>2.5
排除标准
- •4 or more BP medications
- •Intolerance or known prior adverse history from taking the medications amlodipine, aliskiren or valsartan
- •BP >170/110 on screening exam
- •Alcohol intake >12 oz per week
- •Current smoking
- •Recreational drug use
- •Known or suspected secondary hypertension
- •Known history of coronary artery disease, cerebrovascular disease or congestive heart failure
- •History or known kidney disease (eGFR <50cc/min)
- •Diabetes or current metformin use, or HbA1c >=6.5% on screen
- •Steroid use (oral or inhaled, chronic or within the past 6 months)
- •Clinically significant screening lab abnormalities (See attached "Screening Labs Acceptable Ranges")
- •Evidence of ischemia or heart block on screening electrocardiogram (greater than type I-second degree heart block, left bundle branch block, or ST-T wave changes in 2 or more contiguous leads).
- •Acute hospitalizations including surgery in the past 6 months
- •Chronic use of non-steroidal anti-inflammatory or narcotic medications
- •Women who are pregnant or nursing, or wish to become pregnant and/or who can not agree or tolerate two forms of birth control during the study period:
- •Acceptable birth control methods for use in this study are:
- •hormonal methods, such as birth control pills, patches, injections, vaginal ring, or implants
- •barrier methods (such as a condom or diaphragm) used with a spermicide (a foam, cream, or gel that kills sperm)
- •intrauterine device (IUD)
- •abstinence (no sex)
- •Significant concomitant medical illnesses (cancer, chronic active immunological conditions, etc.)
研究组 & 干预措施
Valsartan and Aliskiren
Valsartan 150 mg and Aliskiren (150 mg followed by force titration to 300 mg)
干预措施: Valsartan and Aliskiren (Drug)
Aliskiren
干预措施: Aliskiren (Drug)
Placebo Group
Only taking Amlodipine
干预措施: Amlodipine (Drug)
结局指标
主要结局
Change in Insulin Sensitivity by HOMA at 12 Weeks
时间窗: 12 weeks
The difference (change) in HOMA calculated as Baseline HOMA minus 12-week HOMA value
次要结局
- Aortic Compliance(12 weeks)
研究者
Jonathan S. Williams, MD, MMSc
Jonathan Williams, MD
Brigham and Women's Hospital