Nitrite in Hypertrophic Cardiomyopathy (HCM) Study

University of East Anglia18 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

QUADRUPLE

Enrollment

Conditions

Cardiomyopathy, Hypertrophic

Interventions

Exercise Stress Transthoracic EchocardiogramDIAGNOSTIC_TEST

On the second visit day of this arm, participants will be asked to lie, semi-erect, on an exercise bed for up to 90 minutes. The echocardiogram will be performed at rest and during peak exercise. The exercise will be in the form of a pedal bike. The exercise levels will be worked out from an upright bicycle exercise test completed by the participants prior to randomization.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Cardiac Energetic Status

Change in cardiac PCr/ATP ratio on phosphorus MRS between inorganic sodium nitrate and placebo

Time frame: 3 hours post dose of drug or placebo

Secondary Outcomes

Skeletal Muscle Mitochondrial Oxidative Capacity/Energetic Status

Change in PCr recovery half-time on dynamic phosphorus MRS between inorganic sodium nitrate and placebo

Time frame: 3.5 hours post dose of drug or placebo

Cardiac Diastolic and Systolic Function on exercise

Change in measures of diastolic and systolic function on transthoracic echocardiogram at submaximal exercise between inorganic sodium nitrate and placebo

Time frame: 3 hours post dose of drug or placebo

Cardiac Diastolic and Systolic Function at rest

Change in measures of diastolic and systolic function on transthoracic echocardiogram at rest between inorganic sodium nitrate and placebo

Time frame: 3 hours post dose of drug or placebo

Plasma levels of Nitrate/Nitrite/NOx

Change in blood plasma levels of Nitrate/Nitrite/NOx between inorganic sodium nitrate and placebo

Time frame: 3 hours post dose of drug or placebo

Nitrite in Hypertrophic Cardiomyopathy (HCM) Study

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts