Clinical Research Trial Involves Injecting Patients' Own (Autologous) Stem Cells into Areas of Their Hearts with Poor Blood Flow
Mar 13, 2007
Columbia University Medical Center and NewYork-Presbyterian Hospital is one of the first medical centers in the country participating in a novel clinical trial investigating if a patient's own stem cells can treat a form of severe coronary artery disease. The Autologous Cellular Therapy CD34-Chronic Myocardial Ischemia (ACT34-CMI) trial is the first Phase II adult stem cell therapy study in the U.S. designed to investigate the efficacy, tolerability and safety of blood-derived selected CD34+ stem cells to improve symptoms and clinical outcomes in patients with chronic myocardial ischemia (CMI), a severe form of coronary artery disease.
Myocardial ischemia is a serious heart condition that involves narrowing of coronary arteries and results in limited blood flow to the heart, affecting hundreds of thousands of patients each year. A person who suffers from chronic myocardial ischemia continues to experience insufficient flow of oxygen-rich blood to the heart despite percutaneous (angioplasty, stenting) and/or surgical (coronary bypass) revascularization and optimal medical therapy.
"This promising stem cell therapy may be an alternative for patients without any other means to treat their chest pain," says Dr. Warren Sherman, site principal investigator, interventional cardiologist at NewYork-Presbyterian/Columbia and associate professor of medicine at Columbia University College of Physicians and Surgeons.
The stem cells are thought to work by promoting the growth of new vessels to create new pathways to the heart muscle, ensuring adequate nutrition and alleviating the pain associated with the myocardial ischemia.
ACT34-CMI is a prospective, randomized, double-blind, placebo-controlled study that involves adults with severe myocardial ischemia who are currently on maximal medical therapy and are not suitable candidates for conventional procedures to improve blood flow to the heart, such as angioplasty, stents or coronary artery bypass surgery.
NewYork-Presbyterian is one of what will be between 15 and 20 research sites nationwide participating in the study, which is sponsored by the Cellular Therapies business unit of Baxter Healthcare Corporation. Baxter technology is used to select the subject's own CD34+ stem cells that are under investigation in this trial.
The first step in the ACT34-CMI trial is to establish the baseline frequency and severity of anginal episodes for all study participants. Next, all patients receive a series of subcutaneous injections of a commercially produced protein. The protein helps to release blood-forming CD34+ cells from a subject's bone marrow into the bloodstream. Then, investigators use a cell separation system to collect from the patient's bloodstream, an enriched preparation of cells that contain CD34+ stem cells. When this process is complete, technologists further process the collected stem cells with Baxter's ISOLEX 300i Magnetic Cell Selection System to select the CD34+ stem cells for use in this investigational therapy.
NewYork-Presbyterian's interventional cardiologists then use a catheter-based, non-surgical system to identify ischemic but viable regions of the heart as targets for cell delivery. The researchers then use a special investigational catheter system, developed by Johnson & Johnson, to deliver CD34+ cells, or placebo, into the areas of the heart that have poor blood flow.
Patients are randomly selected to receive either one of two dosing levels of CD34+ stem cells, or placebo.
Researchers are encouraged by reports from the Phase I trial that the therapy appeared to be well-tolerated and no serious adverse events directly related to the stem cell therapy were reported. Through the duration of the 12-month study, there were no deaths or heart attacks. Fifteen of the 18 total Phase I study subjects who received the cells reported feeling better with reductions in chest pain and/or improved exercise capacity. Though not sufficiently powered to prove efficacy, these results did lead the way to the initiation of the Phase II ACT34-CMI trial.
NewYork-Presbyterian Hospital/Weill Cornell Medical Center will also be a participating study site.
The study is funded by the Cellular Therapies business unit of Baxter Healthcare Corporation, of Deerfield, Ill.
For more information, patients may call 866-NYP-NEWS.
Coronary Artery Disease
Coronary artery disease is the most common form of heart disease and is the leading cause of death in the United States. This condition occurs when the coronary arteries and the smaller vessels that supply oxygen-rich blood to the heart muscle become narrowed or blocked by plaque deposits and blood clots. Poor blood flow and blood clots "starve" and injure the heart muscle. The American Heart Association estimates that every year, between 125,000 and 250,000 individuals with coronary artery disease develop chronic myocardial ischemia (CMI), one of the most severe forms of coronary artery disease, which can cause unstable angina, heart attacks and progressive heart failure when adequate blood flow is not restored. CMI develops when the coronary arteries become so diseased that they limit the flow of blood to the heart and send small blood clots downstream, blocking the small blood vessels in the heart. These blockages can result in a series of minor heart attacks that, while they may be too small to notice at the time, in aggregate cause significant long-term damage to the heart muscle and disability to the patient. While cardiologists can restore blood flow in some cases, the heart muscle can be irreversibly damaged, leading to significant disability, progressive heart failure and often death.
Columbia University Medical Center
Columbia University Medical Center provides international leadership in pre-clinical and clinical research, in medical and health sciences education, and in patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, nurses, dentists, and public health professionals at the College of Physicians and Surgeons, the College of Dental Medicine, the School of Nursing, the Mailman School of Public Health, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions.
NewYork-Presbyterian Hospital – based in New York City – is the nation's largest not-for-profit, non-sectarian hospital, with 2,224 beds. It provides state-of-the-art inpatient, ambulatory and preventive care in all areas of medicine at five major centers: NewYork-Presbyterian Hospital/Weill Cornell Medical Center, NewYork-Presbyterian Hospital/Columbia University Medical Center, Morgan Stanley Children's Hospital of NewYork-Presbyterian, NewYork-Presbyterian Hospital/Allen Pavilion and NewYork-Presbyterian Hospital/Westchester Division. One of the largest and most comprehensive health-care institutions in the world, the Hospital is committed to excellence in patient care, research, education and community service. It ranks sixth on U.S.News & World Report's guide to "America's Best Hospitals," has the greatest number of physicians listed in New York magazine's "Best Doctors" issue, and is included among Solucient's top 15 major teaching hospitals. The Hospital has academic affiliations with two of the nation's leading medical colleges: Joan and Sanford I. Weill Medical College of Cornell University and Columbia University College of Physicians and Surgeons.