The trial, just underway at UW Hospital and Clinics, is enrolling subjects in the Autologous Cellular Therapy CD34-Chronic Myocardial Ischemia (ACT34-CMI) Trial. The first patient underwent the procedure March 7. Because the study is randomized and "double-blinded," however, neither the patient nor the research physician knows if he received his own stem cells or a placebo substance.
This trial is the first human Phase II adult stem cell therapy study in the U.S. Its goal is to investigate the efficacy, tolerability, and safety of blood-derived selected stem cells to improve symptoms and clinical outcomes in patients with chronic myocardial ischemia (CMI), a severe form of coronary artery disease.
Myocardial ischemia, which affects hundreds of thousands of people, is a serious heart condition that involves narrowing of coronary arteries and results in limited blood flow to the heart. A person who suffers from chronic myocardial ischemia continues to experience insufficient flow of oxygen-rich blood to the heart despite optimum medical intervention.
This type of therapy - regenerative medicine - treats diseases by using growth factors, genes or stem cells to promote blood vessel or tissue growth," explains Amish Raval, head of cardiovascular regenerative medicine at UW Health.
The goal with this approach, he says, is to promote either angiogenesis, which is the growth of new capillaries; arteriogenesis, or the maturation and enlargement of existing arteries and arterioles; or vasculogenesis, the sprouting of new arteries and arterioles.
The stem-cell study is considered the "gold standard" of research design: a prospective, randomized, double-blind, placebo-controlled study that involves adult subjects who have severe coronary artery disease, are currently on maximal medical therapy and are not suitable candidates for conventional procedures (such as angioplasty, stents, or coronary artery bypass surgery) to improve blood flow to the heart.
UW Hospital and Clinics is one of 15-20 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 of how often the study subjects have chest pain related to their heart disease and the severity of the pain. Next, all subjects receive a series of needle shots, typically delivered under the skin in the arm, thigh or abdomen of a commercially produced protein (granulocyte colony stimulating factor). 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 remove from the subject's bloodstream a mix of cells containing the stem cells. When this process, known as apheresis, is complete, technologists further process the collected stem cells to select the CD34+ stem cells for use in this investigational therapy.
UW Health interventional cardiologists then "map" the heart with a catheter-based, non-surgical system to identify regions of the heart as targets for cell delivery. The researchers then use a special investigational catheter system to deliver either CD34+ cells or placebo into areas of the heart that have poor blood flow. Subjects are randomly selected to receive either one of two dosing levels of CD34+ stem cells, or placebo. Subjects will receive follow-up examinations for 12 months following the investigative procedure.
"The initial results from Phase I of the trial we re encouraging," Raval says. "Subjects reported feeling better with reductions in chest pain and improved exercise capacity during the early stage of the trial. That's encouraging to us."
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 mini-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.