Effect of Inorganic Nitrates on Arterial Hemodynamics and Exercise Capacity
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 17
- 试验地点
- 2
- 主要终点
- Change in Peak exercise efficiency during maximal effort supine-bicycle exercise and peak oxygen consumption (VO2) during a maximal effort supine-bicycle exercise test
研究概览
简要总结
The main objective is to test the hypothesis that inorganic nitrate supplementation will: (1) Improve exercise efficiency and performance; (2) Enhance the systemic vasodilator reserve during exercise and specifically, the vasodilator response in exercising muscle; (3) Reduce arterial wave reflections and arterial load; (4) Improve skeletal muscle mitochondrial function in subjects with heart failure with preserved ejection fraction.
详细描述
This represents a series of double-blind, controlled pilot randomized studies in which the effects of nitrate-rich beetroot juice and nitrate-depleted beetroot juice will be assessed in patients with heart failure and preserved ejection fraction (n=20). A total of 20 subjects will be enrolled over a 1.5 year period and randomized in a cross-over design to a single dose of nitrate-rich beetroot juice and nitrate-depleted beetroot juice. The order of the interventions will be randomized; thus, all subjects will receive the nitrate-rich and nitrate-depleted juice, with a 4-7 day washout period in-between studies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The investigators will enroll 20 subjects >18 years of age who have a diagnosis of heart failure with preserved ejection fraction (>50%) by 2d echocardiography, with current New York Heart Association Class II-IV symptoms.
- •In addition, subjects with heart failure must meet the following inclusion criteria:
- •Chronic treatment with a loop diuretic for control of HF symptoms.
- •If EF is normal, subjects must demonstrate elevated filling pressures as evidenced by at least one of the following: a) left atrial enlargement (LAVI > 32 mL/m2); b) at least stage II diastolic dysfunction; c) Documentation of elevated NT-pro BNP levels or other natriuretic peptide marker (BNP, ANP) according to the laboratory and assay upper limit of normal in the previous year.
- •Stable medical therapy as defined by: (I) No addition or removal of ACE, ARB, beta-blockers, or calcium channel blockers (CCBs) for 30 days. (II) No change in dosage of ACE, ARBs, beta-blockers or CCBs of more than 100% for 30 days. (III) No change in diuretic dose for 10 days.
排除标准
- •Rhythm other than sinus rhythm (i.e., atrial fibrillation).
- •Neuromuscular, orthopedic or other non-cardiac condition that prevents patient from exercising.
- •Valve disease (> mild aortic or mitral stenosis; > moderate aortic or mitral regurgitation).
- •Hypertrophic cardiomyopathy.
- •Known infiltrative or inflammatory myocardial disease (amyloid, sarcoid).
- •Pericardial disease.
- •Primary pulmonary arteriopathy.
- •Have experienced a myocardial infarction or unstable angina, or have undergone percutaneous transluminal coronary angiography (PTCA) or coronary artery bypass grafting (CABG) within 60 days prior to consent, or requires either PTCA or CABG at the time of consent.
- •Other clinically important causes of dyspnea such as morbid obesity or significant lung disease defined by clinical judgment or use of steroids or oxygen for lung disease within the past 6 months.
- •Systolic blood pressure < 110 mmHg or > 180 mm Hg.
- •Diastolic blood pressure < 40 mmHg or > 100 mmHg.
- •Resting heart rate (HR) > 100 bpm.
- •Hemoglobin <10 g/dL.
- •Patients with known severe liver disease (AST > 3x normal, alkaline phosphatase or bilirubin > 2x normal).
- •Patients with a clinically indicated stress test demonstrating significant ischemia within a year of enrollment which was not followed by percutaneous or surgical revascularization.
- •Current therapy with phosphodiesterase inhibitors, such as sildenafil, vardanafil or tadalafil.
- •Known allergies to beetroot or lemon juice.
- •Current use of organic nitrates or phosphodiesterase inhibitors.
- •Pregnancy. Although beetroot juice has not knows teratogenic effects, we feel that not enough data exist in this regard. Therefore, all females patients of reproductive age will be required to undergo a pregnancy test prior to enrollment.
研究组 & 干预措施
Nitrate rich beetroot juice
Subjects with heart failure with preserved ejection fraction will receive 140 mL of Nitrate-rich concentrated beetroot juice (containing 12 mmol of NO-3). This will be a cross-over study. Therefore all subjects will receive both interventions, but the order of the interventions will be randomized.
干预措施: Nitrate rich beetroot juice (Dietary Supplement)
Nitrate depleted beetroot juice
Subjects with heart failure with preserved ejection fraction will receive 140 mL of nitrate-depleted beetroot juice (containing <0.01 mmol of NO-3).This will be a cross-over study. Therefore all subjects will receive both interventions, but the order of the interventions will be randomized.
干预措施: Nitrate depleted beetroot juice (Dietary Supplement)
结局指标
主要结局
Change in Peak exercise efficiency during maximal effort supine-bicycle exercise and peak oxygen consumption (VO2) during a maximal effort supine-bicycle exercise test
时间窗: Baseline study, repeat study 4-7 days later
We will assess the relationship between total power output and total O2 consumption (VO2, assessed via expired gas analysis) during a maximal-effort supine bicycle exercise test.
次要结局
- Change in lower extremity exercise vasodilator reserve (change in femoral vascular resistance between rest and maximal effort supine-bicycle exercise)(Baseline study, repeat study 4-7 days later)
- Change in lower extremity blood flow reserve (change in femoral artery blood flow between rest and maximal effort supine-bicycle exercise)(Baseline study, repeat study 4-7 days later)
- Change in Skeletal Muscle Mitochondrial Oxidative Capacity(Baseline study, repeat study 4-7 days later)
- Change in Arterial wave reflection magnitude(Baseline study, repeat study 4-7 days later)
- Change in Peripheral vascular resistance, total arterial compliance and reflection magnitude during supine bicycle peak exercise(Baseline study, repeat study 4-7 days later)
- Change in submaximal exercise efficiency (O2 consumption per power output during submaximal exercise and standardized handgrip exercise)(Baseline study, repeat study 4-7 days later)
- Change in post-ischemic vasodilatory response(Baseline study, repeat study 4-7 days later)
研究者
Julio A.Chirinos
Director of non-invasive imaging & Assistant Professor of Medicine
Corporal Michael J. Crescenz VA Medical Center