Endothelial Progenitor Cells and Nitric Oxide in Cardiac Rehabilitation Program Participants

Coronary Artery Disease (CAD) Clinical Trial

Official title:

Mechanism and Vascular Effects of Endothelial Progenitor Cell Mobilization in Patients With Coronary Artery Disease Undergoing Cardiac Rehabilitation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00308633
• Other study ID #: 060122
• Secondary ID: 06-H-0122
• Status: Completed
• Phase: N/A
• First received: March 28, 2006
• Last updated: June 30, 2017
• Start date: March 23, 2006

Study information

• Verified date: October 30, 2009
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study will measure blood levels of endothelial progenitor cells (EPCs) and nitric oxide (NO) in patients with coronary artery disease (CAD) who are participating in a 3-month cardiac rehabilitation program at Suburban Hospital in Bethesda, MD. EPCs are a kind of stem cell produced by the bone marrow that can develop into cells found in arteries and in the heart and, therefore, can repair diseased vessels. The study will examine whether the EPCs are affected by exercise and will look at how they may contribute to repair of cells lining the diseased arteries as a result of participation in the rehabilitation program.

People with coronary artery disease may be eligible for this study. Candidates are screened with a medical history, physical examination, electrocardiogram, and blood tests. CAD patients also to a treadmill exercise test.

Volunteers' participation ends at the screening visit. The blood drawn at screening is used to identify EPC specific genes to compare with the EPC genes from patients with CAD.

CAD patients participate in Suburban Hospital's cardiac rehabilitation program. The exercise portion of the program includes 36 sessions of about 60 minutes each, spaced over approximately 3 months. Patients have a baseline blood test at screening and repeat blood tests at the end of each month of participation in the rehabilitation program. Some of the blood will be used for genetic tests to see how genes of the EPCs are changed by the patient's participation in the rehabilitation program.

Description:

Exercise training has long been recommended as a means of improving effort tolerance and reducing morbidity and mortality in patients with coronary artery disease (CAD). One mechanism of benefit may be through improved endothelial function with enhanced nitric oxide (NO) bioactivity. Such an effect may augment blood flow to exercising skeletal muscle and to the myocardium, and reduce vascular inflammation, platelet activation and adherence which could diminish the risk of thrombosis. In 46 patients with CAD, participating in the Suburban Hospital cardiac rehabilitation program (Protocol 03-H-0086), we detected increases in circulating endothelial progenitor cells (EPCs), which may have the capacity to repair diseased or dysfunctional endothelium. In the last 23 participants (following amendment of the protocol) a subset showed increase in whole blood nitrite - a marker of intravascular NO - at completion of program. However, not all patients showed EPC mobilization or increased intravascular NO despite compliant program participation and improved effort tolerance. One possibility is that EPCs from patients who fail to derive vascular benefit as evidenced by increased intravascular NO may have different EPC gene expression profiles at baseline or in response to repetitive exercise, resulting in diminished protection of EPCs against oxidant stress with initiation of apoptosis, compared with EPC gene expression in patients who show evidence of EPC mobilization and endothelial repair. The purpose of our study is to 1) Prospectively demonstrate a relationship between EPC mobilization and increased whole blood nitrite as a marker of improved vascular NO bioactivity due to EPC mobilization, and 2) Determine EPC gene expression profiles, with a focus on activation or suppression of genes whose products regulate intravascular redox potential, apoptosis and growth factor and cytokine secretion. We hypothesize that activation or suppression of critical genes in EPCs at baseline or during exercise may determine EPC mobilization, endothelial differentiation and vascular repair potential as evidenced by increased intravascular NO.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. primary completion date: December 28, 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years and older

Eligibility

• INCLUSION CRITERIA:

Adults older than 21 years.

Coronary artery disease established by angiography.

At least two months interval since myocardial infarction or coronary artery bypass surgery.

At least one month interval since percutaneous coronary intervention or congestive heart failure symptoms.

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.

EXCLUSION CRITERIA:

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) within 2 weeks of referral to the program.

Subjects physically unable to perform cardiac rehabilitation protocol due to neurologic or orthopedic conditions.

Women of childbearing age unless recent pregnancy test is negative.

Lactating women.

Implantable cardioverter-defibrillator (ICD)

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Artery Disease (CAD)
• Coronary Disease
• Myocardial Ischemia

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland
United States	Suburban Hospital	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997 Feb 14;275(5302):964-7. — View Citation

Dimmeler S, Aicher A, Vasa M, Mildner-Rihm C, Adler K, Tiemann M, Rütten H, Fichtlscherer S, Martin H, Zeiher AM. HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway. J Clin Invest. 2001 Aug;108(3):391-7. — View Citation

Kalka C, Masuda H, Takahashi T, Kalka-Moll WM, Silver M, Kearney M, Li T, Isner JM, Asahara T. Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3422-7. — View Citation