Estrogen Receptor Alpha Signaling in Endothelial Cells Exacerbates Arterial Stiffening Via Upregulation of ENaC in Insulin Resistant Females
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 137
- 试验地点
- 1
- 主要终点
- Carotid Femoral Pulse Wave Velocity
研究概览
简要总结
To determine whether treatment with the ENaC inhibitor, amiloride, improves endothelial function and arterial stiffness in obese insulin resistant subjects in a randomized placebo-controlled trial examining pre and postmenopausal women and age-matched men.
详细描述
Overweight/obese males, pre- and post-menopausal females with insulin resistance, 30-70 years of age will be recruited. Following screening, eligible men and women will be randomly assigned to either amiloride (max dose 5mg) or placebo in a double-blinded design manner.
After randomization, subjects will be scheduled for an outpatient visit to the undergo baseline assessment of arterial stiffness (carotid femoral pulse wave velocity - cfPWV) and endothelial function (brachial popliteal artery flow mediated dilation). Subject assessment will be repeated at 12 weeks and at 24 weeks.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 30 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •30 to 70 years of age at randomization
- •Body mass index (BMI) 25.1-50 kg/m2 or waist circumference > 88 cm (> 35 in) in women and >102 cm (>40 in) in men. 3, 4
- •One other characteristic of metabolic syndrome (elevated triglycerides ≥150 mg/dl; HDL cholesterol <40 mg/dl in men and <50 mg/dl in women; blood pressure ≥130/85 mm Hg or treatment for hypertension; impaired fasting glucose (≥100 mg/dl)) or fasting insulin level >10 mU/L (correlates with insulin resistance).
排除标准
- •History of type 1 or type 2 diabetes
- •Known cardiovascular events within the last 12 months (stroke, acute coronary event, revascularization, heart failure hospitalization).
- •History of uncontrolled thyroid disease, chronic liver disease (cirrhosis) or GFR <50 ml/min.
- •Use of potassium sparing medications (angiotensin II receptor blockers, angiotensin converting enzymes inhibitors or mineralocorticoid receptor blockers) or use of potassium supplements.
- •Active cancer (This criterion does not apply to those subjects with basal cell carcinoma or stage 1 squamous cell carcinoma of the skin)
- •Excessive alcohol consumption (>14 drinks/week for men, >7 drinks/week for women)
- •Current tobacco use
- •Non controlled hypertension
- •Participation in regular exercise > 3 days/wk per week at a moderate or vigorous intensity
- •Pregnancy or lactation in women (or women not using contraceptives)
- •Women who plan to become pregnant during the duration of the trial
- •Chronic use of NSAIDs
- •Potassium level > 5.0 mqE/L at time of screening
- •Blood pressure at screening <110/70
研究组 & 干预措施
Placebo
6 months of daily placebo
干预措施: Placebo - Cap (Drug)
Amiloride
6 months of amiloride (max dose 5 mg) treatment
干预措施: Amiloride Pill (Drug)
结局指标
主要结局
Carotid Femoral Pulse Wave Velocity
时间窗: baseline, 3 and 6 mo
cfPWV is the gold standard of arterial stiffness. It was assessd during experimental visits, under the same conditions in a blinded manner
次要结局
未报告次要终点
研究者
Camila Manrique, MD
Associate Professor, Endocrinology
University of Missouri-Columbia