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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Julio A.Chirinos, Philadelphia Veterans Affairs Medical Center
ClinicalTrials.gov Identifier:
NCT01919177
First received: July 22, 2013
Last updated: April 27, 2015
Last verified: April 2015
  Purpose

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.


Condition Intervention Phase
Heart Failure With Normal Ejection Fraction
Dietary Supplement: Nitrate rich beetroot juice
Dietary Supplement: Nitrate depleted beetroot juice
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of Inorganic Nitrates on Arterial Hemodynamics and Exercise Capacity

Resource links provided by NLM:


Further study details as provided by Philadelphia Veterans Affairs Medical Center:

Primary Outcome Measures:
  • Change in Peak exercise efficiency during maximal effort supine-bicycle exercise and peak oxygen consumption (VO2) during a maximal effort supine-bicycle exercise test [ Time Frame: Baseline study, repeat study 4-7 days later ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change in Arterial wave reflection magnitude [ Time Frame: Baseline study, repeat study 4-7 days later ] [ Designated as safety issue: No ]
    Reflection wave magnitude will be assessed using arterial tonometry to arrive at the augmentation index. The data will also be processed using custom designed software for wave separation analysis to quantify the magnitude and timing of the reflected waves.

  • Change in Peripheral vascular resistance, total arterial compliance and reflection magnitude during supine bicycle peak exercise [ Time Frame: Baseline study, repeat study 4-7 days later ] [ Designated as safety issue: No ]
  • Change in lower extremity exercise vasodilator reserve (change in femoral vascular resistance between rest and maximal effort supine-bicycle exercise) [ Time Frame: Baseline study, repeat study 4-7 days later ] [ Designated as safety issue: No ]
  • Change in lower extremity blood flow reserve (change in femoral artery blood flow between rest and maximal effort supine-bicycle exercise) [ Time Frame: Baseline study, repeat study 4-7 days later ] [ Designated as safety issue: No ]
  • Change in submaximal exercise efficiency (O2 consumption per power output during submaximal exercise and standardized handgrip exercise) [ Time Frame: Baseline study, repeat study 4-7 days later ] [ Designated as safety issue: No ]
  • Change in Skeletal Muscle Mitochondrial Oxidative Capacity [ Time Frame: Baseline study, repeat study 4-7 days later ] [ Designated as safety issue: No ]
    The investigators will assess the oxygen consumption recovery kinetics after moderate forearm exercise, using repeated cuff brachial artery occlusions and near-infrared spectroscopy.

  • Change in post-ischemic vasodilatory response [ Time Frame: Baseline study, repeat study 4-7 days later ] [ Designated as safety issue: No ]
    The investigators will assess the post-ischemic vasodilatory response in the forearm using brachial artery pulsed wave Doppler interrogations before and after inflation of a brachial cuff at 200 mmHg for 5 minutes. The investigators will also assess forearm microvascular skeletal muscle flow with near-infrared spectroscopy and forearm skin microvascular flow using laser Doppler.


Enrollment: 17
Study Start Date: January 2013
Study Completion Date: November 2014
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Nitrate rich beetroot juice
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
Subjects will receive 140 mL of Nitrate-rich concentrated beetroot juice.
Other Name: Beet It Stamina Sports shots
Placebo Comparator: Nitrate depleted beetroot juice
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
Subjects will receive 140 mL of nitrate-depleted beetroot juice.
Other Name: Beet It nitrate extracted (depleted) placebo shots

Detailed Description:

This represents a series of double-blind, controlled pilot randomized studies in which the effects of nitrate-rich beetroot juice and nitrate-depleted beetroot juice will be assessed in patients with heart failure and preserved ejection fraction (n=20). A total of 20 subjects will be enrolled over a 1.5 year period and randomized in a cross-over design to a single dose of nitrate-rich beetroot juice and nitrate-depleted beetroot juice. The order of the interventions will be randomized; thus, all subjects will receive the nitrate-rich and nitrate-depleted juice, with a 4-7 day washout period in-between studies.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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.

In addition, subjects with heart failure must meet the following inclusion criteria:

  1. Chronic treatment with a loop diuretic for control of HF symptoms.
  2. 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.
  3. 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.

Exclusion Criteria:

  1. Rhythm other than sinus rhythm (i.e., atrial fibrillation).
  2. Neuromuscular, orthopedic or other non-cardiac condition that prevents patient from exercising.
  3. Valve disease (> mild aortic or mitral stenosis; > moderate aortic or mitral regurgitation).
  4. Hypertrophic cardiomyopathy.
  5. Known infiltrative or inflammatory myocardial disease (amyloid, sarcoid).
  6. Pericardial disease.
  7. Primary pulmonary arteriopathy.
  8. 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.
  9. 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.
  10. Systolic blood pressure < 110 mmHg or > 180 mm Hg.
  11. Diastolic blood pressure < 40 mmHg or > 100 mmHg.
  12. Resting heart rate (HR) > 100 bpm.
  13. Hemoglobin <10 g/dL.
  14. Patients with known severe liver disease (AST > 3x normal, alkaline phosphatase or bilirubin > 2x normal).
  15. Patients with a clinically indicated stress test demonstrating significant ischemia within a year of enrollment which was not followed by percutaneous or surgical revascularization.
  16. Current therapy with phosphodiesterase inhibitors, such as sildenafil, vardanafil or tadalafil.
  17. Known allergies to beetroot or lemon juice.
  18. Current use of organic nitrates or phosphodiesterase inhibitors.
  19. Pregnancy. Although beetroot juice has not knows teratogenic effects, we feel that not enough data exist in this regard. Therefore, all females patients of reproductive age will be required to undergo a pregnancy test prior to enrollment.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01919177

Locations
United States, Pennsylvania
Philadelphia Veterans Affairs Medical Center
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Philadelphia Veterans Affairs Medical Center
Investigators
Principal Investigator: Julio A Chirinos, MD, PhD Philadelphia VA Medical Center & University of Pennsylvania
  More Information

Publications:
Responsible Party: Julio A.Chirinos, Director of non-invasive imaging & Assistant Professor of Medicine, Philadelphia Veterans Affairs Medical Center
ClinicalTrials.gov Identifier: NCT01919177     History of Changes
Other Study ID Numbers: 01415
Study First Received: July 22, 2013
Last Updated: April 27, 2015
Health Authority: United States: Federal Government
United States: Institutional Review Board

Keywords provided by Philadelphia Veterans Affairs Medical Center:
Heart Failure
Arterial hemodynamics
Exercise capacity
Mitochondrial oxidative capacity

Additional relevant MeSH terms:
Heart Failure
Cardiovascular Diseases
Heart Diseases

ClinicalTrials.gov processed this record on July 01, 2015