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| Name | Class |
|---|---|
| Norfolk and Norwich University Hospitals NHS Foundation Trust | OTHER |
| British Medical Research Council | OTHER_GOV |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sodium Nitrate | Active Comparator | 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 Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sodium Nitrate | Drug | Single dose of 14mmol oral inorganic sodium nitrate |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Cardiac Energetic Status | Change in cardiac PCr/ATP ratio on phosphorus MRS between inorganic sodium nitrate and placebo | 3 hours post dose of drug or placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Skeletal Muscle Mitochondrial Oxidative Capacity/Energetic Status | Change in PCr recovery half-time on dynamic phosphorus MRS between inorganic sodium nitrate and placebo | 3.5 hours post dose of drug or placebo |
| Cardiac Diastolic and Systolic Function on exercise |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Brodie L Loudon, MBBS | Contact | 44(0) 1603 591 216 | b.loudon@uea.ac.uk | |
| Michael P Frenneaux, MD | Contact | 44(0) 1603 593 061 | m.frenneaux@uea.ac.uk |
| Name | Affiliation | Role |
|---|---|---|
| Michael P Frenneaux, MD | University of East Anglia | Study Chair |
| Sunil V Nair, MD | Norfolk and Norwich University Hospitals NHS Foundation Trust | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Norfolk and Norwich University Hospitals NHS Foundation Trust | Recruiting | Norwich | Norfolk | NR4 7UY | United Kingdom |
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| ID | Term |
|---|---|
| D002312 | Cardiomyopathy, Hypertrophic |
| ID | Term |
|---|---|
| D009202 | Cardiomyopathies |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D001020 | Aortic Stenosis, Subvalvular |
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| ID | Term |
|---|---|
| C031618 | sodium nitrate |
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This is a placebo-controlled, random-order mechanistic study of oral inorganic sodium nitrate versus placebo in cross-over fashion in patients with non obstructive hypertrophic cardiomyopathy and exercise limitation.
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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.
| Placebo |
| Drug |
Single dose of oral matching placebo |
|
| Phosphorous Magnetic Resonance Spectroscopy | Diagnostic Test | On the first visit day of this arm, participants will be lie inside an MRI scanner to take pictures of the heart. The thigh muscle will then be imaged before, during, and after kicking exercises. |
|
| Exercise Stress Transthoracic Echocardiogram | Diagnostic 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. |
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Change in measures of diastolic and systolic function on transthoracic echocardiogram at submaximal exercise between inorganic sodium nitrate and placebo |
| 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 | 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 | 3 hours post dose of drug or placebo |
| D001024 |
| Aortic Valve Stenosis |
| D000082862 | Aortic Valve Disease |
| D006349 | Heart Valve Diseases |