The Effect of Exercise on Stem Cell Mobilization and Heart Function in Patients Undergoing Cardiac Rehabilitation
|First Received Date ICMJE||January 30, 2003|
|Last Updated Date||March 3, 2008|
|Start Date ICMJE||January 2003|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00053456 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||The Effect of Exercise on Stem Cell Mobilization and Heart Function in Patients Undergoing Cardiac Rehabilitation|
|Official Title ICMJE||Stem Cell Mobilization For Improvement in Vascular Function and Myocardial Perfusion in Patients Undergoing Cardiac Rehabilitation|
This study will look at the effect of a cardiac rehabilitation exercise program on release of stem cells from the bone marrow and on heart function. Stem cells are primitive cells produced and released by the bone marrow, circulate in the bloodstream and develop into white blood cells, red blood cells and platelets. Some stem cells may also develop into other kinds of cells, including those that make up heart muscle, especially if the heart has been damaged or is not getting sufficient blood. Stem cells called endothelial progenitor cells (EPCs) are thought to form new blood vessels that can carry blood to areas of the heart muscle that are oxygen-deprived because of clogged arteries. Previous experiments have shown that some EPCs can be forced out of the bone marrow by exercise. This study will examine whether repeated exercise and lifestyle changes increase the number of EPCs released into the bloodstream and if these cells improve heart and blood vessel function.
Patients 21 years of age and older with coronary artery disease may be eligible for this study. Candidates will be screened with a medical history and physical examination, including a cardiovascular evaluation, and blood tests. The participants will be enrolled in a 2- to 3-month cardiac rehabilitation program that includes 24 to 36 60-minute sessions of exercise, plus instruction on lifestyle changes related to diet, stress management, and relaxation techniques. In addition, participants will undergo the following tests and procedures:
|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 bioactivity. Such an effect may augment blood flow to exercising skeletal muscle and to the myocardium. In this regard, studies in both animals and humans have shown that frequent exercise improves endothelial function as well as blood flow to ischemic myocardium. Exercise-induced improvement in endothelial function is believed to result from up-regulation of endothelial nitric oxide synthase (eNOS) transcription due to repetitive shear stress associated with exercise. However, not all patients show improved endothelial function or myocardial perfusion despite compliant participation in cardiac rehabilitation programs. We hypothesize that endothelial function before and following structured exercise programs may be determined by the presence and function of endothelial progenitor cells (EPCs) that are released from the bone marrow and circulate in the blood stream. Thus, patients who have low baseline or post-exercise EPC levels or function may have limited capacity to improve endothelial function, exercise duration, and myocardial perfusion and function following participation in cardiac rehabilitation programs with repetitive exercise. On the other hand, patients with higher levels of EPCs at baseline or following repetitive exercise, with preserved capacity of EPCs to form endothelial cells, may show improved endothelial function, exercise duration, and myocardial perfusion and function as a result of repetitive exercise. The primary endpoint of this study will be improvement in endothelial function as determined by flow-mediated dilator responsiveness of the brachial artery at 2-3 months of repetitive exercise in the program compared with baseline measurements. Secondary endpoints include treadmill exercise duration and magnetic resonance imaging (MRI)-determined regional cardiac perfusion by gadolinium distribution during pharmacologic stress at 2-3 months compared with baseline measurements. EPCs will be identified by characteristic cell surface markers and by colony-forming ability at specific time-points of the study, with correlations determined between EPCs at baseline or the increase in EPCs following repetitive exercise, and the primary and secondary endpoints. We propose that patients most likely, and least likely, to benefit from a cardiac rehabilitation program may be identified on the basis of circulating EPCs.|
|Study Type ICMJE||Observational|
|Study Design ICMJE||Not Provided|
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Not Provided|
|Study Population||Not Provided|
|Condition ICMJE||Coronary Arteriosclerosis|
|Intervention ICMJE||Not Provided|
|Study Groups/Cohorts||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Estimated Completion Date||January 2006|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
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 medical condition that might prohibit safe participation in cardiac rehabilitation.
Subject understands protocol and provides written, informed consent in addition to willingness to comply with specified follow-up evaluations.
Significant structural heart disease (e.g. hypertrophic or dilated cardiomyopathy, valvular heart disease) as determined by echocardiography.
Angina pectoris that is prolonged in duration (greater than 20 minutes), or does not respond to nitroglycerin (2 tablets).
Subject physically unable to perform cardiac rehabilitation protocol due to neurologic or orthopedic conditions.
Hypersensitivity to organic nitrates.
Women of childbearing age unless recent pregnancy test is negative.
Known hypersensitivity to dipyridamole or to gadolinium if patient eligible for MRI study.
|Ages||Child, Adult, Senior|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00053456|
|Other Study ID Numbers ICMJE||030086, 03-H-0086|
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|Plan to Share Data||Not Provided|
|IPD Description||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Heart, Lung, and Blood Institute (NHLBI)|
|Collaborators ICMJE||Not Provided|
|Investigators ICMJE||Not Provided|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||January 2006|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP