Nitrite in Hypertrophic Cardiomyopathy (HCM) Study

University of East Anglia

Status and phase: Unknown; Phase 1

Conditions: Cardiomyopathy, Hypertrophic

Treatments: Diagnostic Test: Exercise Stress Transthoracic Echocardiogram; Drug: Sodium Nitrate; Drug: Placebo; Diagnostic Test: Phosphorous Magnetic Resonance Spectroscopy

Study type: Interventional

Funder types: Other

Identifiers

NCT03251287

201323

Details and patient eligibility

About

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.

Enrollment: 18 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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18 participants in 2 patient groups, including a placebo group

Sodium Nitrate

Active Comparator group

Description:

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.

Treatment:

Diagnostic Test: Phosphorous Magnetic Resonance Spectroscopy

Diagnostic Test: Exercise Stress Transthoracic Echocardiogram

Drug: Sodium Nitrate

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Diagnostic Test: Phosphorous Magnetic Resonance Spectroscopy

Diagnostic Test: Exercise Stress Transthoracic Echocardiogram

Drug: Placebo