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

April 27, 2015 updated by: Julio A.Chirinos, Corporal Michael J. Crescenz VA Medical Center

Effect of Inorganic Nitrates on Arterial Hemodynamics and Exercise Capacity

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
17

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Philadelphia Veterans Affairs Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 Names:
  • 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 Names:
  • Beet It nitrate extracted (depleted) placebo shots

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in Arterial wave reflection magnitude
Time Frame: Baseline study, repeat study 4-7 days later
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.
Baseline study, repeat study 4-7 days later
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
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)
Time Frame: Baseline study, repeat study 4-7 days later
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)
Time Frame: Baseline study, repeat study 4-7 days later
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)
Time Frame: Baseline study, repeat study 4-7 days later
Baseline study, repeat study 4-7 days later
Change in Skeletal Muscle Mitochondrial Oxidative Capacity
Time Frame: Baseline study, repeat study 4-7 days later
The investigators will assess the oxygen consumption recovery kinetics after moderate forearm exercise, using repeated cuff brachial artery occlusions and near-infrared spectroscopy.
Baseline study, repeat study 4-7 days later
Change in post-ischemic vasodilatory response
Time Frame: Baseline study, repeat study 4-7 days later
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.
Baseline study, repeat study 4-7 days later

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Corporal Michael J. Crescenz VA Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2014

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 22, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 6, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 8, 2013

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 28, 2015

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 27, 2015

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 01415

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