Coronary Artery DiseasePhase 2NCT00043628
Stem Cell Mobilization to Treat Chest Pain and Shortness of Breath in Patients With Coronary Artery Disease
A Phase 2 study testing Stem Cell Mobilization in people with Coronary Artery Disease, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
This two-part study will determine whether stem cells (primitive cells produced by the bone marrow that can develop into blood cells or other types of cells) can be pushed out into the bloodstream, relocate in the heart, and grow new heart muscle and blood vessels in patients with chest pain caused by narrowing of… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Coronary Artery Disease
- What is being tested?
- Stem Cell Mobilization
- Type of treatment
- Surgery or procedure
- How many people
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2002to Feb 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
Who may be able to join
- Adults older than 21 years.
- Functional class (CCS) 3 or 4 angina attributable to atherosclerotic CAD, despite medical management, not optimal for mechanical revascularization due to coronary anatomy, co-morbidity, or patient preference.
- Left ventricular ejection fraction greater than 30 percent.
- Inducible myocardial ischemia by dobutamine stress MRI.
- No congestive heart failure symptoms within 2 months.
- No active infection.
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- Normal renal function:creatinine less than 1.5 mg/dl, proteinuria less than 1plus
- Normal liver function: bilirubin less than 1.5 mg/dl, transaminases within normal limits.
- Normal blood count: WBC 3000-10000/microliter, granulocytes greater than 1500/microliter; platelet count greater than 150,000/microliter, Hgb greater than 12.5 g/dl.
- Subject understands protocol and provides written, informed consent in addition to willingness to comply with specified follow-up evaluations.
Who cannot join
- Myocardial infarction within 2 months.
- Crescendo angina: Angina pectoris that is prolonged in duration (greater than 30 minutes), does not respond to nitroglycerin (3 tablets), or is occurring with increasing frequency over the previous two weeks.
- Significant structural heart disease (e.g. hypertrophic or dilated cardiomyopathy, valvular heart disease) as determined by echocardiography.
- Patients who are HIV positive, have chronic inflammatory diseases, or are on chronic immunosuppressive medications.
- Women of childbearing age unless recent pregnancy test is negative.
- Lactating women.
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- Known active malignancy or prior history of hematologic malignancy.
- Participation in unrelated research involving an investigational pharmacological agent 30 days before planned G-CSF dosing.
- Contraindication for MRI.
- Known hypersensitivity to E. coli-derived proteins or to gadolinium.
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 as Therapy for Chronic Myocardial Ischemia in Patients With Coronary Artery Disease
This two-part study will determine whether stem cells (primitive cells produced by the bone marrow that can develop into blood cells or other types of cells) can be pushed out into the bloodstream, relocate in the heart, and grow new heart muscle and blood vessels in patients with chest pain caused by narrowing of their coronary (heart) arteries. The new blood vessels may enable patients to do more activities before experiencing chest pain. Part 1 of the study will evaluate in a small number of patients whether an increase in white blood cells following administration of G-CSF (a drug used to move stem cells from the bone marrow to the bloodstream) is safe in people with coronary heart disease. Part 2 will evaluate the effects of the circulating stem cells on heart function.
Patients 21 years of age and older with coronary artery blockage that limits blood flow to the heart (as shown by coronary angiography within 6 months of entering the study) and causes chest pain that interferes with the ability to carry out daily living activities may be eligible for this study. Candidates will be screened with blood tests, an exercise test, magnetic resonance imaging (MRI), and 24-hour Holter monitoring of heart rate and rhythm. Participants will undergo the following tests and procedures:
Read more
Part 1: Patients will be hospitalized at the NIH Clinical Center for 5 days. On the first day after admission, an indwelling catheter (short plastic tube) will be placed in an arm vein to avoid multiple needle sticks for blood sampling. Patients will then exercise on a treadmill. Blood samples will be drawn before the exercise test and 2 hours after the test. The next 2 days, patients will receive a daily injection of G-CSF under the skin. Blood samples will be drawn every day for 5 days to monitor the effect of G-CSF on moving cells into the bloodstream. Additional samples will be drawn to determine the effects of G-CSF on the number of stem cells that become heart cells, as well as any effects on blood clotting ability. After discharge for the hospital, patients will return to the clinic 2 weeks after the initiation of G-CSF treatment for a physical examination, blood tests, and a treadmill exercise test. One month after the initiation of treatment, patients will return to the clinic for a physical examination, blood tests, treadmill exercise test, an MRI study, and fitting with a Holter monitor for 24-hour heart monitoring.
Part 2: Patients will be hospitalized at the NIH Clinical Center for 5 days, undergoing the same procedures as in Part 1, except they will receive G-CSF for 5 days instead of 2. They will also undergo the same procedures detailed for the 2-week and 1-month follow-up visits. Then, at 3 months they will again return to the clinic for a physical examination, routine blood tests, and a treadmill exercise test. This concludes formal participation in the study. However, patients are requested to return to the outpatient clinic once a year for follow-up.
Read the detailed description
Percutaneous transluminal coronary angioplasty or stenting and coronary artery bypass surgery are effective therapies for relief of angina caused by coronary artery disease (CAD). However many patients with CAD have failed attempts at conventional revascularization or remain symptomatic despite optimized anti-ischemic medical therapy. For this growing number of patients, there is a need for novel therapeutic approaches. Experimental studies in animal models indicate that primitive pluripotential cells (or 'stem' cells) from bone marrow may localize to ischemic myocardium, differentiate along endothelial, smooth muscle, and cardiomyocyte lineages, and improve cardiac performance. A recent report has suggested that granulocyte-macrophage colony stimulating factor, which mobilizes stem cells from bone marrow into the circulation, may improve collateral blood flow to ischemic myocardium in patients with CAD. The purpose of this protocol is to test the effectiveness of a related cytokine, granulocyte colony stimulating factor (G-CSF), that more potently mobilizes stem cells from bone marrow, for the relief of myocardial ischemia and improvement in myocardial contractility during stress in patients with CAD who are not good candidates for conventional revascularization, or who do not want further attempts at conventional revascularization, and who remain symptomatic on medical therapy.
Our hypothesis is that G-CSF will improve blood flow to the myocardium and the left ventricular contractile response to stress by mobilizing pluripotential cells from bone marrow with localization to ischemic regions of the heart, resulting in development of new arteries and regeneration of contractile cardiomyocytes. The primary end-point of the Phase I (safety) component of this study is absence of cardiovascular adverse events associated with increased white blood cell counts following G-CSF administration in patients with CAD. The secondary end-point for Phase I is determination of platelet aggregation and coagulation activation before and during G-CSF administration. The primary endpoint of the Phase II (efficacy) component of this study is improvement in magnetic resonance imaging (MRI)-determined regional left ventricular contractility and gadolinium distribution (as an index of blood flow) during stress at 1 month following G-CSF administration compared with pretreatment baseline measurements. Secondary Phase II end-points will include determinations of 1) efficacy of stem and endothelial progenitor cell (EPC) mobilization by G-CSF, and 2) changes in treadmill exercise duration associated with G-CSF treatment. Demonstration of safe and effective cytokine-induced mobilization of stem cells with cardiac benefit could result in an important therapeutic option for CAD patients who have few alternatives for the relief of myocardial ischemia and angina pectoris.
- Conditions
- Coronary Artery Disease
- Being tested
- Stem Cell Mobilization
- Keywords
- Progenitor Cells, MRI, Coronary Blood Flow, Hematopoiesis, Myocardial Contractility, Coronary Artery Disease, CAD, Heart Disease
- Medical subject headings
- Coronary Artery Disease, Heart Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stem Cell MobilizationProcedure or surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2002 (estimated)
- Study startAug 2002
- Study completionFeb 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
- 35 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00043628
- Sponsor's protocol ID
- 020264
- Other IDs
- 02-H-0264
- Status last verified
- Feb 2005
- First submitted
- 9 Aug 2002
- 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
- Stem Cell Mobilization as Therapy for Chronic Myocardial Ischemia in Patients With Coronary Artery Disease
- ClinicalTrials.gov ID
- NCT00043628
- Acronym / sponsor ID
- 020264
- Conditions
- Coronary Artery Disease
- Keywords
- Progenitor Cells, MRI, Coronary Blood Flow, Hematopoiesis, Myocardial Contractility, Coronary Artery Disease, CAD, Heart Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- Aug 2002
- Study completion
- Feb 2005
- First posted
- 12 Aug 2002 (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 two-part study will determine whether stem cells (primitive cells produced by the bone marrow that can develop into blood cells or other types of cells) can be pushed out into the bloodstream, relocate in the heart, and grow new heart muscle and blood vessels in patients with chest pain caused by narrowing of their coronary (heart) arteries. The new blood vessels may enable patients to do more activities before experiencing chest pain. Part 1 of the study will evaluate in a small number of patients whether an increase in white blood cells following administration of G-CSF (a drug used to move stem cells from the bone marrow to the bloodstream) is safe in people with coronary heart disease. Part 2 will evaluate the effects of the circulating stem cells on heart function.
Patients 21 years of age and older with coronary artery blockage that limits blood flow to the heart (as shown by coronary angiography within 6 months of entering the study) and causes chest pain that interferes with the ability to carry out daily living activities may be eligible for this study. Candidates will be screened with blood tests, an exercise test, magnetic resonance imaging (MRI), and 24-hour Holter monitoring of heart rate and rhythm. Participants will undergo the following tests and procedures:
Part 1: Patients will be hospitalized at the NIH Clinical Center for 5 days. On the first day after admission, an indwelling catheter (short plastic tube) will be placed in an arm vein to avoid multiple needle sticks for blood sampling. Patients will then exercise on a treadmill. Blood samples will be drawn before the exercise test and 2 hours after the test. The next 2 days, patients will receive a daily injection of G-CSF under the skin. Blood samples will be drawn every day for 5 days to monitor the effect of G-CSF on moving cells into the bloodstream. Additional samples will be drawn to determine the effects of G-CSF on the number of stem cells that become heart cells, as well as any effects on blood clotting ability. After discharge for the hospital, patients will return to the clinic 2 weeks after the initiation of G-CSF treatment for a physical examination, blood tests, and a treadmill exercise test. One month after the initiation of treatment, patients will return to the clinic for a physical examination, blood tests, treadmill exercise test, an MRI study, and fitting with a Holter monitor for 24-hour heart monitoring.
Part 2: Patients will be hospitalized at the NIH Clinical Center for 5 days, undergoing the same procedures as in Part 1, except they will receive G-CSF for 5 days instead of 2. They will also undergo the same procedures detailed for the 2-week and 1-month follow-up visits. Then, at 3 months they will again return to the clinic for a physical examination, routine blood tests, and a treadmill exercise test. This concludes formal participation in the study. However, patients are requested to return to the outpatient clinic once a year for follow-up.
Detailed description
Percutaneous transluminal coronary angioplasty or stenting and coronary artery bypass surgery are effective therapies for relief of angina caused by coronary artery disease (CAD). However many patients with CAD have failed attempts at conventional revascularization or remain symptomatic despite optimized anti-ischemic medical therapy. For this growing number of patients, there is a need for novel therapeutic approaches. Experimental studies in animal models indicate that primitive pluripotential cells (or 'stem' cells) from bone marrow may localize to ischemic myocardium, differentiate along endothelial, smooth muscle, and cardiomyocyte lineages, and improve cardiac performance. A recent report has suggested that granulocyte-macrophage colony stimulating factor, which mobilizes stem cells from bone marrow into the circulation, may improve collateral blood flow to ischemic myocardium in patients with CAD. The purpose of this protocol is to test the effectiveness of a related cytokine, granulocyte colony stimulating factor (G-CSF), that more potently mobilizes stem cells from bone marrow, for the relief of myocardial ischemia and improvement in myocardial contractility during stress in patients with CAD who are not good candidates for conventional revascularization, or who do not want further attempts at conventional revascularization, and who remain symptomatic on medical therapy.
Our hypothesis is that G-CSF will improve blood flow to the myocardium and the left ventricular contractile response to stress by mobilizing pluripotential cells from bone marrow with localization to ischemic regions of the heart, resulting in development of new arteries and regeneration of contractile cardiomyocytes. The primary end-point of the Phase I (safety) component of this study is absence of cardiovascular adverse events associated with increased white blood cell counts following G-CSF administration in patients with CAD. The secondary end-point for Phase I is determination of platelet aggregation and coagulation activation before and during G-CSF administration. The primary endpoint of the Phase II (efficacy) component of this study is improvement in magnetic resonance imaging (MRI)-determined regional left ventricular contractility and gadolinium distribution (as an index of blood flow) during stress at 1 month following G-CSF administration compared with pretreatment baseline measurements. Secondary Phase II end-points will include determinations of 1) efficacy of stem and endothelial progenitor cell (EPC) mobilization by G-CSF, and 2) changes in treadmill exercise duration associated with G-CSF treatment. Demonstration of safe and effective cytokine-induced mobilization of stem cells with cardiac benefit could result in an important therapeutic option for CAD patients who have few alternatives for the relief of myocardial ischemia and angina pectoris.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- Adults older than 21 years.
- Functional class (CCS) 3 or 4 angina attributable to atherosclerotic CAD, despite medical management, not optimal for mechanical revascularization due to coronary anatomy, co-morbidity, or patient preference.
- Left ventricular ejection fraction greater than 30 percent.
- Inducible myocardial ischemia by dobutamine stress MRI.
- No congestive heart failure symptoms within 2 months.
Key exclusion criteria (10 listed)
- Myocardial infarction within 2 months.
- Crescendo angina: Angina pectoris that is prolonged in duration (greater than 30 minutes), does not respond to nitroglycerin (3 tablets), or is occurring with increasing frequency over the previous two weeks.
- Significant structural heart disease (e.g. hypertrophic or dilated cardiomyopathy, valvular heart disease) as determined by echocardiography.
- Patients who are HIV positive, have chronic inflammatory diseases, or are on chronic immunosuppressive medications.
- 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.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Stem Cell Mobilization | Procedure or surgery | – |
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 Stem Cell Mobilization 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.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 10 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.
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.