Dietary Nitrate and Nitrite to Increase Nitric Oxide in Patients With Coronary Artery Disease

NCT00069654 | Completed Phase 2

• 2 other identifiers: 03031203-H-0312
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

This study will determine whether dietary nitrates and nitrites can produce nitric oxide in the body and dilate blood vessels in patients with coronary artery disease. Nitric oxide is normally made by endothelial cells that line blood vessels. It plays an important role in maintaining the normal function of arteries by keeping them open and preventing damage from substances such as cholesterol in the blood stream. Coronary artery disease is caused by atherosclerosis (hardening of the arteries or build-up of cholesterol and scar tissue within the walls of the arteries). Once arteries become clogged, the ability of the endothelium to produce nitric oxide diminishes considerably and may speed up the disease process, leading to shortness of breath, chest pain, and an increased risk of heart attack or stroke. Patients 21 years of age and older with coronary artery disease may be eligible for this study. Participants will have a medical history and physical examination, electrocardiogram (recording of the electrical activity of the heart), echocardiogram (ultrasound test of the heart), treadmill exercise stress test (see below), and will meet with a dietitian. They will be hospitalized at the NIH Clinical Center on two occasions. For 1 week before each admission, they will follow a diet prescribed by an NIH nutritionist. The diet before one admission will be high in nitrates and nitrites, and the diet before the other admission will be low in nitrates and nitrites. Each admission will last 4 days, during which participants will undergo the following tests:

• Forearm blood flow study: Small tubes are placed in the artery and vein at the inside of the elbow of the dominant arm (right- or left-handed) and a small tube is placed in a vein of the other arm. The tubes are used for infusing saline (salt water) and for drawing blood samples. A pressure cuff is placed around the upper part of the dominant arm, and a rubber band device called a strain gauge is also placed around the arm to measure blood flow. When the cuff is inflated, blood flows into the arm, stretching the strain gauge at a rate proportional to the flow. Maximum grip-strength of the dominant arm is measured with a dynamometer. Forearm blood flow is measured and blood samples are drawn at the following times: 20 minutes after the tubes are placed; during a hand-grip exercise; and 4 minutes after the exercise is completed.
• Brachial artery reactivity study: This test measures h...

Conditions

Coronary Arteriosclerosis

Keywords

Endothelium; Atherosclerosis; Vasodilation; Ischemia; Exercise; Coronary Artery Disease; CAD

Outcome Measures

Primary Outcomes (1)

• Comparison of forearm blood flow during exercise after 3 days of the nitrate-nitrite-enriched diet to forearm blood flow during exercise after 3 days of the nitrate/nitrite-restricted diet.

  Measured on day 4 of the nitrite/nitrate enriched and restricted diet

Secondary Outcomes (1)

• Comparison of effects of high versus low nitrate/nitrite diets on exercise forearm blood flow between the two cohorts of patients.

  Measured on day 4 of the nitrite/nitrate enriched and restricted diet.

Interventions

Forearm blood flow study PROCEDURE

Brachial artery reactivity study PROCEDURE

Treadmill exercise test PROCEDURE

Eligibility Criteria

• Age: 22 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults older than 21 years.
• Coronary artery disease established by angiography.
• No myocardial infarction within 1 month.
• Left ventricular ejection fraction greater than 30%.
• No congestive heart failure symptoms within 2 months.
• Subject provides written, informed consent.

You may not qualify if:

• Significant structural heart disease (e.g. hypertrophic or dilated cardiomyopathy, valvular heart disease) as determined by echocardiography.
• Subject physically unable to perform treadmill exercise due to neurologic or orthopedic conditions.
• Hypersensitivity to organ nitrates.
• Insulin-dependant diabetes mellitus.
• Coumadin therapy (because of vitamin K content of green leafy vegetables).
• Women of childbearing age unless recent pregnancy test is negative.
• Lactating women.
• Unwillingness to adhere to dietary requirements or allergy to necessary components of diets, as determined during interview by the dietician.
• Surgical or disease-related diminished acid secretion.
• Significant non-cardiac disease.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980 Nov 27;288(5789):373-6. doi: 10.1038/288373a0.

  PMID: 6253831 BACKGROUND

• Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987 Jun 11-17;327(6122):524-6. doi: 10.1038/327524a0.

  PMID: 3495737 BACKGROUND

• Palmer RM, Ashton DS, Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature. 1988 Jun 16;333(6174):664-6. doi: 10.1038/333664a0.

  PMID: 3131684 BACKGROUND

MeSH Terms

Conditions

Coronary Artery Disease; Atherosclerosis; Aneurysm; Ischemia; Motor Activity

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Behavior

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: NIH

Study Record Dates

• First Submitted: September 29, 2003
• First Posted: September 30, 2003
• Study Start: September 25, 2003
• Primary Completion: May 18, 2009
• Last Updated: July 2, 2017

Record last verified: 2009-05-18

Locations

US (1)