The Effects of Inorganic Nitrate on Cardiac Muscle in Angina

Study Overview
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Brief Summary
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Previous studies have shown that interventions which modestly increase blood nitrite_ improve skeletal muscle function on exercise while sparing oxygen, and have been also shown to open up the blood flow during periods of oxygen deprivation. Inorganic nitrate in the diet is absorbed into the bloodstream, concentrated and reduced by bacteria in the mouth to nitrite, which is then absorbed into the bloodstream. . The purpose of this study is to look at the effects of oral inorganic nitrate supplementation on clinical markers of heart ischaemia and the frequency of angina.

Official Title
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The Effects of Inorganic Nitrate on Cardiac Muscle: Physiology, Pharmacology and Therapeutic Potential in Patients Suffering From Angina

Conditions
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Chronic Stable Angina

Intervention / Treatment
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* Drug: Sodium Nitrate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 18 and over with chronic stable angina (≥2 months duration). Inclusion Criteria Following screening visit: A positive exercise ECG (1mmSTD at J+0.08 seconds) on a modified Bruce protocol treadmill exercise test. A positive dobutamine stress echocardiogram, and/or a positive myocardial perfusion scan (MPI), and/or a positive coronary angiogram. Exclusion Criteria: Unable to do exercise test Women of child bearing potential If of a racial origin at risk of glucose-6-phosphate dehydrogenase (G6PD) deficiency, G6PD will be excluded prior to inclusion in the study Resting STD>=1mm NYHA 3 or 4 HF or LVEF<45% Myocardial infarction or revascularisation within the last two months Left bundle branch block (LBBB)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>Inorganic Nitrate | Drug: Sodium Nitrate<br> <br> |
| Placebo Comparator: placebo<br>Placebo | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to 1mm ST depression | The primary outcome is to assess whether oral nitrate treatment increase the time to 1mm ST depression on a modified Bruce protocol exercise test | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Onset of chest pain | Time to onset of chest pain on a modified Bruce protocol exercise test | 12 weeks | 
| Change in TDI systolic peak velocity | Change in Tissue Doppler Imaging (TDI) systolic peak velocity in ischaemic wall segments | 12 weeks | 
| Angina frequency | Angina frequency | 12 weeks | 
| GTN use frequency | GTN use frequency | 12 weeks | 
| Questionnaire Score | Modified Seattle Angina Questionnaire Score | 12 weeks | 
| Nitrate/Nitrite | Measurements of Nitrate and Nitrite in plasma | 12 weeks | 
| Metabolic, inflammatory and angiogenic plasma markers | Measurements of metabolic, inflammatory and angiogenic markers in plasma | 12 weeks |