Coronary Artery DiseasePhase 2NCT00090558
Effect of Nitric Oxide Donor on Endothelial Progenitor Cells in Patients With Coronary Artery Disease
A Phase 2 study testing nitroglycerin in people with Coronary Artery Disease, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Coronary Artery Disease
- What is being tested?
- nitroglycerin
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2004to Sep 2005
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
PATIENT INCLUSION CRITERIA
- 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.
- No associated medical, neurological or orthopedic condition that might prohibit safe performance of exercise.
- Subject understands protocol and provides written, informed consent in addition to willingness to comply with specified follow-up evaluations.
PATIENT EXCLUSION CRITERIA
- Significant structural heart disease (e.g. hypertrophic or dilated cardiomyopathy, valvular heart disease) as determined by echocardiography.
- History of recent (within 2 months) rest or nocturnal angina
- Organic nitrate (e.g., nitroglycerin) use other than study medication within 24 hours of exercise testing
- Hypersensitivity to organic nitrates.
- Women of childbearing age unless recent pregnancy test is negative.
- Lactating women.
ELIGIBILITY CRITERIA - HEALTHY SUBJECTS
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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Heart, Lung and Blood Institute (NHLBI)
Bethesda, Maryland, 20892
About this study
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.
Read the 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.
- Conditions
- Coronary Artery Disease
- Being tested
- nitroglycerin
- Keywords
- Atherosclerosis, Bone Marrow, Exercise, Endothelium, Nitroglycerin, Coronary Artery Disease, CAD
- Medical subject headings
- Coronary Artery Disease, Atherosclerosis, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
nitroglycerinDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2004 (estimated)
- Study startAug 2004
- Study completionSep 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Enrolment
- 30 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00090558
- Sponsor's protocol ID
- 040268
- Other IDs
- 04-H-0268
- Status last verified
- Sep 2005
- First submitted
- 27 Aug 2004
- Last updated
- 4 Mar 2008
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Nitric Oxide Donor on Endothelial Progenitor Cells in Patients With Coronary Artery Disease
- ClinicalTrials.gov ID
- NCT00090558
- Acronym / sponsor ID
- 040268
- Conditions
- Coronary Artery Disease
- Keywords
- Atherosclerosis, Bone Marrow, Exercise, Endothelium, Nitroglycerin, Coronary Artery Disease, CAD
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- Aug 2004
- Study completion
- Sep 2005
- First posted
- 27 Aug 2004 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| nitroglycerin | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing nitroglycerin in people with Coronary Artery Disease, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2008.