Effect of Inorganic Nitrates (Beetroot Juice) on Arterial Hemodynamics and Exercise Capacity

NCT01919177 | Completed Phase 2

• 1 other identifier: 01415
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

The main objective is to test the hypothesis that inorganic nitrate supplementation will: (1) Improve exercise efficiency and performance; (2) Enhance the systemic vasodilator reserve during exercise and specifically, the vasodilator response in exercising muscle; (3) Reduce arterial wave reflections and arterial load; (4) Improve skeletal muscle mitochondrial function in subjects with heart failure with preserved ejection fraction.

Conditions

Heart Failure With Normal Ejection Fraction

Keywords

Heart Failure; Arterial hemodynamics; Exercise capacity; Mitochondrial oxidative capacity

Outcome Measures

Primary Outcomes (1)

• Change in Peak exercise efficiency during maximal effort supine-bicycle exercise and peak oxygen consumption (VO2) during a maximal effort supine-bicycle exercise test

  We will assess the relationship between total power output and total O2 consumption (VO2, assessed via expired gas analysis) during a maximal-effort supine bicycle exercise test.

  Baseline study, repeat study 4-7 days later

Secondary Outcomes (7)

• Change in Arterial wave reflection magnitude

  Baseline study, repeat study 4-7 days later

• Change in Peripheral vascular resistance, total arterial compliance and reflection magnitude during supine bicycle peak exercise

  Baseline study, repeat study 4-7 days later

• Change in lower extremity exercise vasodilator reserve (change in femoral vascular resistance between rest and maximal effort supine-bicycle exercise)

  Baseline study, repeat study 4-7 days later

• Change in lower extremity blood flow reserve (change in femoral artery blood flow between rest and maximal effort supine-bicycle exercise)

  Baseline study, repeat study 4-7 days later

• Change in submaximal exercise efficiency (O2 consumption per power output during submaximal exercise and standardized handgrip exercise)

  Baseline study, repeat study 4-7 days later

Study Arms (2)

Nitrate rich beetroot juice

ACTIVE COMPARATOR

Subjects with heart failure with preserved ejection fraction will receive 140 mL of Nitrate-rich concentrated beetroot juice (containing 12 mmol of NO-3). This will be a cross-over study. Therefore all subjects will receive both interventions, but the order of the interventions will be randomized.

Dietary Supplement: Nitrate rich beetroot juice

Nitrate depleted beetroot juice

PLACEBO COMPARATOR

Subjects with heart failure with preserved ejection fraction will receive 140 mL of nitrate-depleted beetroot juice (containing \<0.01 mmol of NO-3).This will be a cross-over study. Therefore all subjects will receive both interventions, but the order of the interventions will be randomized.

Dietary Supplement: Nitrate depleted beetroot juice

Interventions

Nitrate rich beetroot juice DIETARY_SUPPLEMENT

Subjects will receive 140 mL of Nitrate-rich concentrated beetroot juice.

Also known as: Beet It Stamina Sports shots

Nitrate rich beetroot juice

Nitrate depleted beetroot juice DIETARY_SUPPLEMENT

Subjects will receive 140 mL of nitrate-depleted beetroot juice.

Also known as: Beet It nitrate extracted (depleted) placebo shots

Nitrate depleted beetroot juice

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The investigators will enroll 20 subjects \>18 years of age who have a diagnosis of heart failure with preserved ejection fraction (\>50%) by 2d echocardiography, with current New York Heart Association Class II-IV symptoms.
• Chronic treatment with a loop diuretic for control of HF symptoms.
• If EF is normal, subjects must demonstrate elevated filling pressures as evidenced by at least one of the following: a) left atrial enlargement (LAVI \> 32 mL/m2); b) at least stage II diastolic dysfunction; c) Documentation of elevated NT-pro BNP levels or other natriuretic peptide marker (BNP, ANP) according to the laboratory and assay upper limit of normal in the previous year.
• Stable medical therapy as defined by: (I) No addition or removal of ACE, ARB, beta-blockers, or calcium channel blockers (CCBs) for 30 days. (II) No change in dosage of ACE, ARBs, beta-blockers or CCBs of more than 100% for 30 days. (III) No change in diuretic dose for 10 days.

You may not qualify if:

• Rhythm other than sinus rhythm (i.e., atrial fibrillation).
• Neuromuscular, orthopedic or other non-cardiac condition that prevents patient from exercising.
• Valve disease (\> mild aortic or mitral stenosis; \> moderate aortic or mitral regurgitation).
• Hypertrophic cardiomyopathy.
• Known infiltrative or inflammatory myocardial disease (amyloid, sarcoid).
• Pericardial disease.
• Primary pulmonary arteriopathy.
• Have experienced a myocardial infarction or unstable angina, or have undergone percutaneous transluminal coronary angiography (PTCA) or coronary artery bypass grafting (CABG) within 60 days prior to consent, or requires either PTCA or CABG at the time of consent.
• Other clinically important causes of dyspnea such as morbid obesity or significant lung disease defined by clinical judgment or use of steroids or oxygen for lung disease within the past 6 months.
• Systolic blood pressure \< 110 mmHg or \> 180 mm Hg.
• Diastolic blood pressure \< 40 mmHg or \> 100 mmHg.
• Resting heart rate (HR) \> 100 bpm.
• Hemoglobin \<10 g/dL.
• Patients with known severe liver disease (AST \> 3x normal, alkaline phosphatase or bilirubin \> 2x normal).
• Patients with a clinically indicated stress test demonstrating significant ischemia within a year of enrollment which was not followed by percutaneous or surgical revascularization.

Sponsors & Collaborators

• Corporal Michael J. Crescenz VA Medical Center: lead

Study Sites (1)

Philadelphia Veterans Affairs Medical Center

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (3)

• American Thoracic Society; American College of Chest Physicians. ATS/ACCP Statement on cardiopulmonary exercise testing. Am J Respir Crit Care Med. 2003 Jan 15;167(2):211-77. doi: 10.1164/rccm.167.2.211. No abstract available.

  PMID: 12524257 BACKGROUND

• Manetos C, Dimopoulos S, Tzanis G, Vakrou S, Tasoulis A, Kapelios C, Agapitou V, Ntalianis A, Terrovitis J, Nanas S. Skeletal muscle microcirculatory abnormalities are associated with exercise intolerance, ventilatory inefficiency, and impaired autonomic control in heart failure. J Heart Lung Transplant. 2011 Dec;30(12):1403-8. doi: 10.1016/j.healun.2011.08.020. Epub 2011 Oct 7.

  PMID: 21982360 BACKGROUND

• Zamani P, Rawat D, Shiva-Kumar P, Geraci S, Bhuva R, Konda P, Doulias PT, Ischiropoulos H, Townsend RR, Margulies KB, Cappola TP, Poole DC, Chirinos JA. Effect of inorganic nitrate on exercise capacity in heart failure with preserved ejection fraction. Circulation. 2015 Jan 27;131(4):371-80; discussion 380. doi: 10.1161/CIRCULATIONAHA.114.012957. Epub 2014 Dec 22.

  PMID: 25533966 RESULT

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Julio A Chirinos, MD, PhD

  Philadelphia VA Medical Center & University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of non-invasive imaging & Assistant Professor of Medicine

Study Record Dates

• First Submitted: July 22, 2013
• First Posted: August 8, 2013
• Study Start: January 1, 2013
• Primary Completion: September 1, 2014
• Study Completion: November 1, 2014
• Last Updated: April 28, 2015

Record last verified: 2015-04

Locations

US (1)