Nitrite in Hypertrophic Cardiomyopathy (HCM) Study
- Conditions
- Cardiomyopathy, Hypertrophic
- Interventions
- Drug: PlaceboDiagnostic Test: Phosphorous Magnetic Resonance SpectroscopyDiagnostic Test: Exercise Stress Transthoracic Echocardiogram
- Registration Number
- NCT03251287
- Lead Sponsor
- University of East Anglia
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 18
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Sodium Nitrate Phosphorous Magnetic Resonance Spectroscopy 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. Sodium Nitrate Exercise Stress Transthoracic Echocardiogram 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. Placebo 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. Placebo Phosphorous Magnetic Resonance Spectroscopy 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. Placebo Exercise Stress Transthoracic Echocardiogram 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. Sodium Nitrate 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.
- Primary Outcome Measures
Name Time Method Cardiac Energetic Status 3 hours post dose of drug or placebo Change in cardiac PCr/ATP ratio on phosphorus MRS between inorganic sodium nitrate and placebo
- Secondary Outcome Measures
Name Time Method Skeletal Muscle Mitochondrial Oxidative Capacity/Energetic Status 3.5 hours post dose of drug or placebo Change in PCr recovery half-time on dynamic phosphorus MRS between inorganic sodium nitrate and placebo
Cardiac Diastolic and Systolic Function on exercise 3 hours post dose of drug or placebo Change in measures of diastolic and systolic function on transthoracic echocardiogram at submaximal exercise between inorganic sodium nitrate and placebo
Cardiac Diastolic and Systolic Function at rest 3 hours post dose of drug or placebo Change in measures of diastolic and systolic function on transthoracic echocardiogram at rest between inorganic sodium nitrate and placebo
Plasma levels of Nitrate/Nitrite/NOx 3 hours post dose of drug or placebo Change in blood plasma levels of Nitrate/Nitrite/NOx between inorganic sodium nitrate and placebo
Trial Locations
- Locations (1)
Norfolk and Norwich University Hospitals NHS Foundation Trust
🇬🇧Norwich, Norfolk, United Kingdom