Coronary ArteriosclerosisNCT00053456
The Effect of Exercise on Stem Cell Mobilization and Heart Function in Patients Undergoing Cardiac Rehabilitation
An observational study of Coronary Arteriosclerosis, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Coronary Arteriosclerosis
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2003to Jan 2006
- Phase
- Observational
- 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
Who may be able to join
- 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.
Who cannot join
- 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.
- Lactating women.
- Known hypersensitivity to dipyridamole or to gadolinium if patient eligible for MRI study.
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
Official title: 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:
- Brachial reactivity study: This test measures how well the arteries widen. The patients rest for 30 minutes, and then an ultrasound device is placed over the artery just above the elbow. The device measures the size of the artery and blood flow through it before and after the patient is given a spray of nitroglycerin under the tongue.
- Blood tests for EPC levels and genetic testing: These measure EPCs and determine whether certain genes that may regulate EPC function are turned on or off. Genes are made up of DNA, the molecules that lead to the production of proteins by cells. Some of these proteins may be important in releasing EPCs from the bone marrow to travel in the bloodstream to the heart and repair blood vessels and muscle cells.
- Treadmill exercise testing: Patients exercise on a treadmill with continuous monitoring of the heartbeat and frequent measurements of oxygen saturation, using a finger clip device. The patient continues to exercise until moderate chest pain, shortness of breath, or fatigue develops.
- Questionnaire: Patients fill out a 15-minute questionnaire about their general physical and mental health status at the first and last visits to the clinic.
- Magnetic resonance imaging (MRI) of the heart: Patients who are eligible to undergo MRI have this test twice during the study, once before beginning the rehabilitation program and again after completing the program. The MRI shows heart function and blood flow in the heart. For this test, the patient lies on a stretcher inside a long narrow cylinder (the scanner). During the scan, the drug dipyridamole, which increases blood flow to the heart, is infused into a vein of the hand or arm. Another drug, gadolinium, is also infused to brighten the images produced.
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 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.
- Conditions
- Coronary Arteriosclerosis
- Keywords
- Endothelium, Nitric Oxide, Myocardial Ischemia, Exercise, Endothelial Progenitor Cells
- Medical subject headings
- Coronary Artery Disease, Myocardial Ischemia, Motor Activity
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2003 (estimated)
- Study startJan 2003
- Study completionJan 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Coronary ArteriosclerosisStudies 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
- Observational
- Enrolment
- 50 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00053456
- Sponsor's protocol ID
- 030086
- Other IDs
- 03-H-0086
- Status last verified
- Jan 2006
- First submitted
- 30 Jan 2003
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Ades PA. Cardiac rehabilitation and secondary prevention of coronary heart disease. N Engl J Med. 2001 Sep 20;345(12):892-902. doi: 10.1056/NEJMra001529. No abstract available.
PubMed 11565523Belardinelli R, Georgiou D, Ginzton L, Cianci G, Purcaro A. Effects of moderate exercise training on thallium uptake and contractile response to low-dose dobutamine of dysfunctional myocardium in patients with ischemic cardiomyopathy. Circulation. 1998 Feb 17;97(6):553-61. doi: 10.1161/01.cir.97.6.553.
PubMed 9494025Bogle RG, Baydoun AR, Pearson JD, Mann GE. Regulation of L-arginine transport and nitric oxide release in superfused porcine aortic endothelial cells. J Physiol. 1996 Jan 1;490 ( Pt 1)(Pt 1):229-41. doi: 10.1113/jphysiol.1996.sp021138.
PubMed 8745290
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
- Stem Cell Mobilization For Improvement in Vascular Function and Myocardial Perfusion in Patients Undergoing Cardiac Rehabilitation
- ClinicalTrials.gov ID
- NCT00053456
- Acronym / sponsor ID
- 030086
- Conditions
- Coronary Arteriosclerosis
- Keywords
- Endothelium, Nitric Oxide, Myocardial Ischemia, Exercise, Endothelial Progenitor Cells
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 50 participants
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- Jan 2003
- Study completion
- Jan 2006
- First posted
- 30 Jan 2003 (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.
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:
- Brachial reactivity study: This test measures how well the arteries widen. The patients rest for 30 minutes, and then an ultrasound device is placed over the artery just above the elbow. The device measures the size of the artery and blood flow through it before and after the patient is given a spray of nitroglycerin under the tongue.
- Blood tests for EPC levels and genetic testing: These measure EPCs and determine whether certain genes that may regulate EPC function are turned on or off. Genes are made up of DNA, the molecules that lead to the production of proteins by cells. Some of these proteins may be important in releasing EPCs from the bone marrow to travel in the bloodstream to the heart and repair blood vessels and muscle cells.
- Treadmill exercise testing: Patients exercise on a treadmill with continuous monitoring of the heartbeat and frequent measurements of oxygen saturation, using a finger clip device. The patient continues to exercise until moderate chest pain, shortness of breath, or fatigue develops.
- Questionnaire: Patients fill out a 15-minute questionnaire about their general physical and mental health status at the first and last visits to the clinic.
- Magnetic resonance imaging (MRI) of the heart: Patients who are eligible to undergo MRI have this test twice during the study, once before beginning the rehabilitation program and again after completing the program. The MRI shows heart function and blood flow in the heart. For this test, the patient lies on a stretcher inside a long narrow cylinder (the scanner). During the scan, the drug dipyridamole, which increases blood flow to the heart, is infused into a vein of the hand or arm. Another drug, gadolinium, is also infused to brighten the images produced.
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 design
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
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.
- Background: PubMed 11565523Ades PA. Cardiac rehabilitation and secondary prevention of coronary heart disease. N Engl J Med. 2001 Sep 20;345(12):892-902. doi: 10.1056/NEJMra001529. No abstract available.
- Background: PubMed 9494025Belardinelli R, Georgiou D, Ginzton L, Cianci G, Purcaro A. Effects of moderate exercise training on thallium uptake and contractile response to low-dose dobutamine of dysfunctional myocardium in patients with ischemic cardiomyopathy. Circulation. 1998 Feb 17;97(6):553-61. doi: 10.1161/01.cir.97.6.553.
- Background: PubMed 8745290Bogle RG, Baydoun AR, Pearson JD, Mann GE. Regulation of L-arginine transport and nitric oxide release in superfused porcine aortic endothelial cells. J Physiol. 1996 Jan 1;490 ( Pt 1)(Pt 1):229-41. doi: 10.1113/jphysiol.1996.sp021138.
Related trials for Coronary Arteriosclerosis
Not yet recruitingPhase 4
Roxadustat and Myocardial Injury After Off-Pump Coronary Artery Bypass Surgery
Coronary Artery Disease, Coronary Artery Bypass Grafting
RecruitingObservational study
Preoperative Gastric Ultrasound and Left Ventricular Function in Coronary Artery Bypass Surgery
Coronary Artery Disease, Left Ventricular Systolic Dysfunction
Active, not recruiting
The OCTOBER Trial - European Trial on Optical Coherence Tomography Optimized Bifurcation Event Reduction (OCTOBER)
Ischaemic Heart Disease, Ischemic Heart Disease
RecruitingEarly Phase 1
Thiamine Intervention and Coronary Artery Bypass Grafting
Coronary Heart Disease, Coronary Artery Bypass Grafting
Active, not recruitingObservational study
A Longitudinal Cohort Study to Evaluate Cardiovascular Risk Factors and Disease in Haiti
Hypertension, Diabetes
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?
An observational study of Coronary Arteriosclerosis, 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.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
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.
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?
On the ClinicalTrials.gov record for NCT00053456, which also lists 3 linked publications.
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.