Mechanistic Study of the Effect of Inorganic Sodium Nitrate on Cardiac and Skeletal Muscle Metabolic Efficiency in Patients With Hypertrophic Cardiomyopathy
试验速览
- 阶段
- 1 期
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Cardiac Energetic Status
研究概览
简要总结
Inorganic nitrate, which is found at high levels in green leafy vegetables, is reduced to nitrite by bacteria in the mouth, swallowed, and absorbed in the stomach into the blood. Studies have shown that increasing the blood levels of nitrite improves the way that muscles use oxygen and energy during exercise, and potentially blood flow.
Some people (~1 in 500) suffer from a type of genetic heart condition known as hypertrophic cardiomyopathy (HCM). This condition means that the muscle in the heart does not use energy well and becomes larger than average, meaning that they have to tap into the heart's 'energy reserves'. It is not known if nitrite has the same beneficial effects on heart muscle as on other muscles in the body. Our study will explore the mechanism by which nitrite may improve the function and energy status of the heart in HCM.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
This will be a double blind study. The placebo and active treatments will appear identical and will be dispensed in identical containers. All trial patients, care providers, outcome assessors and data analysts will remain blind throughout the study.
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, aged between 18 and 80 years.
- •Able to provide informed consent.
- •Able to understand basic instructions in English.
- •A diagnosis of hypertrophic cardiomyopathy based on conventional transthoracic echocardiogram guidelines: left ventricular wall thickness >1.5cm in the absence of sufficient alternative cause.
- •Exercise limited by symptoms on exertion (NYHA Class II symptoms or greater).
- •PeakVO2 <80% on baseline CPEX.
- •The absence of resting LV outflow tract obstruction (peak gradient <30 mm Hg) on TTE.
排除标准
- •Significant medical, surgical or psychiatric disease that in the opinion of the patient's attending physician would affect subject safety or influence the study outcome.
- •Contraindications for undergoing MRI.
- •Hypotension with a systolic blood pressure <90mmHg.
- •Severe anaemia with a plasma haemoglobin level <8.0g/dL.
- •Known glucose-6-phosphate dehydrogenase (G6PD) deficiency or G6PD deficiency measured at screening in males of African, Asian or Mediterranean decent.
- •Female subjects of childbearing potential.
- •Haemodynamically significant valve disease.
- •Predisposed to acute on chronic limb ischemia evident from a history of claudication or known peripheral arterial disease.
研究组 & 干预措施
Sodium Nitrate
Following entry into the study, patients will receive a single dose of oral inorganic sodium nitrate (14mmol) on two separate visits, or matching placebo, in random order (i.e. 2x nitrate visits first or 2x placebo visits first) in a cross-over fashion.
干预措施: Sodium Nitrate (Drug)
Sodium Nitrate
Following entry into the study, patients will receive a single dose of oral inorganic sodium nitrate (14mmol) on two separate visits, or matching placebo, in random order (i.e. 2x nitrate visits first or 2x placebo visits first) in a cross-over fashion.
干预措施: Phosphorous Magnetic Resonance Spectroscopy (Diagnostic Test)
Sodium Nitrate
Following entry into the study, patients will receive a single dose of oral inorganic sodium nitrate (14mmol) on two separate visits, or matching placebo, in random order (i.e. 2x nitrate visits first or 2x placebo visits first) in a cross-over fashion.
干预措施: Exercise Stress Transthoracic Echocardiogram (Diagnostic Test)
Placebo
Following entry into the study, patients will receive a single dose of oral inorganic sodium nitrate (14mmol) on two separate visits, or matching placebo, in random order (i.e. 2x nitrate visits first or 2x placebo visits first) in a cross-over fashion.
干预措施: Placebo (Drug)
Placebo
Following entry into the study, patients will receive a single dose of oral inorganic sodium nitrate (14mmol) on two separate visits, or matching placebo, in random order (i.e. 2x nitrate visits first or 2x placebo visits first) in a cross-over fashion.
干预措施: Phosphorous Magnetic Resonance Spectroscopy (Diagnostic Test)
Placebo
Following entry into the study, patients will receive a single dose of oral inorganic sodium nitrate (14mmol) on two separate visits, or matching placebo, in random order (i.e. 2x nitrate visits first or 2x placebo visits first) in a cross-over fashion.
干预措施: Exercise Stress Transthoracic Echocardiogram (Diagnostic Test)
结局指标
主要结局
Cardiac Energetic Status
时间窗: 3 hours post dose of drug or placebo
Change in cardiac PCr/ATP ratio on phosphorus MRS between inorganic sodium nitrate and placebo
次要结局
- Skeletal Muscle Mitochondrial Oxidative Capacity/Energetic Status(3.5 hours post dose of drug or placebo)
- Cardiac Diastolic and Systolic Function on exercise(3 hours post dose of drug or placebo)
- Cardiac Diastolic and Systolic Function at rest(3 hours post dose of drug or placebo)
- Plasma levels of Nitrate/Nitrite/NOx(3 hours post dose of drug or placebo)