McGowan Institute for Regenerative Medicine
affiliated faculty member Joon Sup Lee, M.D. (pictured), clinical director of the UPMC Cardiovascular Institute, associate chief in the Division of Cardiology at the University of Pittsburgh School of Medicine, and associate professor in the Department of Medicine at the University of Pittsburgh, served as the principal investigator of the Pittsburgh clinical trial site for the Autologous Cellular Therapy CD34-Chronic Myocardial Ischemia (ACT34-CMI) Trial (March 2006-2009 and October 2007-June 2010, sponsored by Baxter Healthcare Corporation). The ACTC34-CMI trial was the first human Phase II adult stem cell therapy study in the United States 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.
The results of this Phase II adult stem cell therapy study indicated that an injection of stem cells into the heart could offer hope to many of the 850,000 Americans whose chest pain doesn't subside even with medicine, angioplasty, or surgery. Patients who received the new treatment reported half as many chest pain episodes and improved exercise capability compared to those who received a placebo.
The study was the first randomized, controlled trial of stem-cell therapy to show significant improvements in both chest pain and exercise tolerance – the two debilitating features of "refractory" angina, or chest pain that persists in spite of medication, surgery, or angioplasty.
Researchers used the patients' CD34+ stem cells, which circulate through the blood and are important in forming new blood vessels. The stem cell injection is meant to create new vessels in the diseased heart muscle, improving blood flow to the area and reducing episodes of chest pain.
In the study, 167 patients at 26 U.S. medical centers were randomized to one of three injection groups: low dose (100,000 CD34+ cells/kg body weight); high dose (500,000 CD34+ cells/kg body weight); or a placebo.
Normally, there are too few CD34+ cells to provide enough for therapy. So, researchers used a drug to increase the number of the cells in the body before collecting them. Using a catheter threaded into the heart, the researchers injected CD34+ cells into muscle identified as receiving insufficient blood.
Among the study's findings:
- At 6 months, low-dose patients had 6.8 angina attacks per week – significantly fewer than 10.9 per week for those receiving placebo. High-dose patients had fewer episodes than the placebo group, but the difference was not statistically significant, so the results could be due to chance.
- At 12 months, the low-dose group had 6.3 episodes per week and the placebo patients had 11 episodes per week; high-dose patients had fewer angina episodes than the control group, but the difference remained insignificant. "It is not rare in clinical trials for high doses to be less effective than low doses," Losordo said.
- The improvement in exercise tolerance at 6 months in low-dose patients was 139 seconds, which was significantly greater compared to the 69-second tolerance of the placebo patients. The high-dose group had a greater, but not significant, improvement than the placebo patients.
- At 6 and 12 months, both treated groups were using less nitroglycerine to treat angina than control patients, but the differences were not significant.
About a third of participants had minor elevations of troponin, an enzyme that signals a heart attack when accompanied by changes in an electrocardiogram (EKG), researchers said. However, patients felt no chest pain and experienced no EKG changes.
Later this year, the researchers will begin a phase III trial of the therapy, the level usually required before the Food and Drug Administration considers approving a drug.
Illustration: University of Pittsburgh Medical Center.
American Heart Association News Release (07/07/11)
Science Daily (07/08/11)
McGowan Institute for Regenerative Medicine Clinical Translation: Cell Therapy for Angina
Bio: Dr. Joon Sup Lee
Abstract (Circulation Research: American Heart Association; 111.245993, published online before print July 7, 2011.)