Stem Cell Mobilization to Treat Chest Pain and Shortness of Breath in Patients With Coronary Artery Disease

NCT00043628 | Completed Phase 2

• 2 other identifiers: 02026402-H-0264
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Coronary Artery Disease

Keywords

Progenitor Cells; MRI; Coronary Blood Flow; Hematopoiesis; Myocardial Contractility; Coronary Artery Disease; CAD; Heart Disease

Interventions

Stem Cell Mobilization PROCEDURE

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Heart, Lung and Blood Institute (NHLBI)

Bethesda, Maryland, 20892, United States

Location

MeSH Terms

Conditions

Coronary Artery Disease; Heart Diseases

Interventions

Hematopoietic Stem Cell Mobilization

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 2
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: August 9, 2002
• First Posted: August 12, 2002
• Study Start: August 1, 2002
• Study Completion: February 1, 2005
• Last Updated: March 4, 2008

Record last verified: 2005-02

Locations

US (1)