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Effects of Dietary Nitrate Supplementation on Cardiorespiratory Control in Chronic Heart Failure

Phase 4
Completed
Conditions
Heart Failure, Systolic
Interventions
Dietary Supplement: Nitrate supplementation
Dietary Supplement: Placebo
Registration Number
NCT02401126
Lead Sponsor
Queen's University
Brief Summary

The main purpose of this study is to determine whether dietary nitrate supplementation via concentrated beetroot juice improves central and peripheral cardiovascular control and physical capacity in patients with systolic heart failure.

Detailed Description

Chronic heart failure (CHF) is a leading cause of morbidity and mortality worldwide. Although affecting the heart at first, it is now recognized that disability is largely due to impaired cerebral and skeletal muscle blood flow and consequently microvascular oxygenation. Reduced muscle oxygenation compromises oxidative metabolism and thus contractile performance. Impaired cerebral oxygenation not only reduces motor output (thus exacerbating muscle fatigue) but also constitutes a predictor of cerebral ischemic events and an independent prognostic risk factor.

Reduced levels of the vasodilator nitric oxide (NO) contribute to impaired blood flow and oxygenation in CHF. Development of new effective therapeutic strategies is therefore crucial given that current pharmacological treatment has failed to abrogate oxygenation deficits in CHF patients. Emerging evidence shows that nitrate serves as an alternative source for NO and improves muscle blood flow and oxygenation in health. Another striking feature of nitrate is that it can improve muscle work efficiency, a tenet of physiology that was once considered immutable.

Objective: To investigate systematically the role of dietary nitrate supplementation on central and peripheral cardiovascular function in CHF patients.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
13
Inclusion Criteria
  • previous diagnosis of systolic heart failure (left ventricular ejection fraction <40%) under optimized clinical treatment as judged by the accompanying physician.
Exclusion Criteria
  • hospital admission in the previous 6 weeks;
  • exercise training program in the previous 6 months;
  • nitrate therapy (e.g., isosorbide dinitrate);
  • tabagism;
  • any condition that could interfere with the ability to exercise;
  • diagnosed psychiatric or cognitive disorders;
  • type I insulin-dependent diabetes mellitus;
  • excessively over-weight (BMI>35kg/m²);
  • other diagnosed cardiorespiratory disorders (e.g., chronic obstructive pulmonary disease, peripheral artery disease).

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Nitrate supplementationNitrate supplementationConcentrated nitrate-rich beetroot juice
PlaceboPlaceboNitrate-depleted beetroot juice
Primary Outcome Measures
NameTimeMethod
Exercise tolerance8 days

Cycle ergometer exercise test to the limit of tolerance

Secondary Outcome Measures
NameTimeMethod
Plasma nitrate and nitrite concentrations8 days

Assessed by chemiluminescence

Central and peripheral fatigue8 days

Assessed by transcutaneous femoral nerve magnetic stimulation

Skeletal muscle and cerebral blood flow and oxygenation8 days

Assessed by near-infrared spectroscopy and the rate of appearance of the optically-dense indocyanine green dye

Neuromuscular activity8 days

Assessed by electromyography

Dyspnea and leg effort scores8 days

Evaluated via a 10-point Borg scale

Cognitive performance8 days

Assessed by computer-based tests

Cardiorespiratory responses to exercise8 days

Non-invasive evaluation of cardiac (mean arterial pressure, cardiac output, stroke volume and heart rate) and pulmonary gas exchange (e.g., minute ventilation and oxygen uptake) responses during the transition from rest to exercise

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