Effect of Nitric Oxide Donor on Endothelial Progenitor Cells in Patients With Coronary Artery Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00090558
Recruitment Status : Completed
First Posted : August 27, 2004
Last Update Posted : March 4, 2008
Information provided by:
National Institutes of Health Clinical Center (CC)

Brief Summary:

Regular exercise reduces the risk of heart problems, in part because it improves the work of the endothelium (the cells that line blood vessels). Exercise appears to release precursor cells from the bone marrow that will later become endothelial cells. A molecule called nitric oxide (NO) appears to be involved in this release. However, some heart patients do not improve their endothelial function despite regular exercise. The researchers believe that the heart disease in these patients may interfere with the normal relationship between exercise and endothelial function. This study is designed to test whether giving a patient nitroglycerin (which is converted to NO in the bloodstream) will increase the release of endothelial precursor cells from the bone marrow. If the study succeeds, it may lead to improved healing of arteries in heart disease patients.

Adults may be eligible for this study if they have coronary artery disease and do not take nitroglycerin or nitroglycerin-like medication on a daily basis.

Volunteers will be admitted to the Clinical Center on 2 separate nights at least 1 week apart. On the morning after each admission, volunteers will have blood drawn from an arm vein for laboratory tests, and then walk on a treadmill until fatigue or discomfort prevents further exercise, or until asked to stop. On one of their admissions, volunteers will receive 1 tablet of nitroglycerin under the tongue shortly before the treadmill test. Volunteers will be monitored by EKGs and blood pressure tests during the treadmill tests, and will have more blood drawn at about 15 minutes and 24 hours after each treadmill test. Researchers will examine the levels of endothelial precursor cells and nitric oxide in the blood samples taken before and after exercise.

Condition or disease Intervention/treatment Phase
Coronary Artery Disease Drug: nitroglycerin Phase 2

Detailed Description:
Exercise training has long been recommended as a means of improving cardiac function and reducing morbidity and mortality in patients with coronary artery disease (CAD). One mechanism of benefit may be through improved endothelial function and enhanced nitric oxide (NO) bioactivity, which may improve blood flow to exercising skeletal muscle and to the myocardium. We have recently determined in a collaborative study with the Suburban Hospital, however, that many CAD patients do not show improved endothelial function despite compliant participation in a three month cardiac rehabilitation program with exercise three times weekly. The initial data from this study suggest that improvement in endothelial function may be dependent on the release of endothelial progenitor cells (EPCs) from the bone marrow into the circulation in response to the stimulus of repetitive exercise, with the potential of repairing damaged endothelium and improving endothelial function and NO release. Thus, patients who have poor EPC mobilization responses to exercise may have limited capacity to improve endothelial function over time and, conversely, patients with higher EPC mobilization responses to exercise may show improved endothelial function as a result of vascular repair. Animal models indicate that NO is necessary for EPC mobilization during exercise, likely through nitrosation reactions with key signaling proteins within bone marrow. In many CAD patients, NO release from endothelium and transport in blood to bone marrow may be compromised because of atherosclerotic vascular disease, and thus limit EPC mobilization and vascular repair. We hypothesize that the exogenous administration of NO to CAD patients may enhance EPC mobilization from bone marrow in response to exercise. If successful, administration of an NO donor (such as nitroglycerin) prior to exercise may extend the benefit of exercise to endothelial function-and thus cardiovascular risk-in a larger segment of CAD patients participating in cardiac rehabilitation programs.

Study Type : Interventional  (Clinical Trial)
Enrollment : 30 participants
Primary Purpose: Treatment
Official Title: Effect of Nitric Oxide Donor on Endothelial Progenitor Cells in Patients With Coronary Artery Disease
Study Start Date : August 2004
Study Completion Date : September 2005

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  1. Adults older than 21 years.
  2. Coronary artery disease established by angiography.
  3. No myocardial infarction within 1 month.
  4. Left ventricular ejection fraction greater than 30%.
  5. No congestive heart failure symptoms within 2 months.
  6. No associated medical, neurological or orthopedic condition that might prohibit safe performance of exercise.
  7. Subject understands protocol and provides written, informed consent in addition to willingness to comply with specified follow-up evaluations.


  1. Significant structural heart disease (e.g. hypertrophic or dilated cardiomyopathy, valvular heart disease) as determined by echocardiography.
  2. History of recent (within 2 months) rest or nocturnal angina
  3. Organic nitrate (e.g., nitroglycerin) use other than study medication within 24 hours of exercise testing
  4. Hypersensitivity to organic nitrates.
  5. Women of childbearing age unless recent pregnancy test is negative.
  6. Lactating women.


Healthy subjects must be older than 50 years of age (to approximate the anticipated age of CAD patients), without known CAD, and be free of the following risk factors: blood pressure greater than 140/90 mmHg, fasting glucose greater than 110 mg/dL, smoking, total cholesterol greater than 250 mg/dL. Healthy subjects taking chronic prescription medications will be excluded.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00090558

United States, Maryland
National Heart, Lung and Blood Institute (NHLBI)
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Heart, Lung, and Blood Institute (NHLBI) Identifier: NCT00090558     History of Changes
Other Study ID Numbers: 040268
First Posted: August 27, 2004    Key Record Dates
Last Update Posted: March 4, 2008
Last Verified: September 2005

Keywords provided by National Institutes of Health Clinical Center (CC):
Bone Marrow
Coronary Artery Disease

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arterial Occlusive Diseases
Vascular Diseases
Nitric Oxide
Nitric Oxide Donors
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Free Radical Scavengers
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Protective Agents