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

Dietary Nitrate Supplementation and Cardiorespiratory Control in Chronic Heart Failure: a Randomized, Placebo-controlled Trial

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.

Study Overview

• Status: Completed
• Conditions: Heart Failure, Systolic
• Intervention / Treatment: Dietary supplement: Nitrate supplementation; Dietary supplement: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Nitrate supplementation; Concentrated nitrate-rich beetroot juice	Dietary supplement: Nitrate supplementation; Nitrate supplementation: concentrated nitrate-rich beetroot juice (2 x 70 ml/day; approximately 10 mmol nitrate/day; Beet It, James White Drinks, Ipswich, UK) for 8 consecutive days.; Other Names: Concentrated nitrate-rich beetroot juice
Placebo Comparator: Placebo; Nitrate-depleted beetroot juice	Dietary supplement: Placebo; Placebo: nitrate-depleted beetroot juice (2 x 70 ml/day; approximately 0.01 mmol nitrate/day; Beet It, James White Drinks, Ipswich, UK) for 8 consecutive days. The placebo juice is similar to the concentrated beetroot juice in appearance, texture, smell and taste and is obtained by removing nitrate ions from the latter.; Other Names: Nitrate-depleted beetroot juice

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exercise tolerance	Cycle ergometer exercise test to the limit of tolerance	8 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma nitrate and nitrite concentrations	Assessed by chemiluminescence	8 days
Central and peripheral fatigue	Assessed by transcutaneous femoral nerve magnetic stimulation	8 days
Skeletal muscle and cerebral blood flow and oxygenation	Assessed by near-infrared spectroscopy and the rate of appearance of the optically-dense indocyanine green dye	8 days
Neuromuscular activity	Assessed by electromyography	8 days
Dyspnea and leg effort scores	Evaluated via a 10-point Borg scale	8 days
Cognitive performance	Assessed by computer-based tests	8 days
Cardiorespiratory responses to exercise	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	8 days

Collaborators and Investigators

• Sponsor: Queen's University
• Investigators: Principal Investigator: J. Alberto Neder, MD, PhD, Queen's University

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: March 24, 2015
• First Submitted That Met QC Criteria: March 24, 2015
• First Posted (Estimate): March 27, 2015

Study Record Updates

• Last Update Posted (Estimate): May 2, 2016
• Last Update Submitted That Met QC Criteria: April 29, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Heart Failure, Systolic
• Other Study ID Numbers: 6012610