A Phase 2A, Randomized, Double-Blind, Placebo-Controlled Study of Single or Repeated Intravenous Administration of UC-MSCs in Ischemic Cardiomyopathy (CATO)
Abstract
This proposal addresses the Fiscal Year 2022 (FY22) Peer Reviewed Medical Research Program (PRMRP) Topic Area of Cardiomyopathy and the Strategic Goal of treatment, including the Goal of developing less-invasive treatment technologies. We will study ischemic cardiomyopathy (ICM), which is a progressive deterioration of heart function caused by myocardial infarctions (heart attacks), resulting in heart failure. ICM is the most common form of cardiomyopathy and accounts for approximately half of all cases of heart failure. It is a common, lethal, disabling, and expensive condition. The number of patients with heart failure in the U.S. has reached epidemic proportions (~6 million) and continues to escalate as the population ages. The 5-year survival for those admitted to the hospital with heart failure is ~50%, worse than many cancers. These patients experience a high burden of morbidity and mortality and consume major health care resources, including frequent, recurrent hospitalizations. The burden of heart failure is disproportionately greater among minorities. There is, therefore, an unmet need to develop novel therapies for heart failure that are efficacious, safe, scalable, cost-effective, non-invasive, and thus widely applicable. This is the objective of the proposed project. Several studies have shown that cell-based therapy using mesenchymal stromal cells (MSCs) holds great promise as a new approach to produce improvements in heart function in patients with heart failure due to ICM. If these effects can be clinically established and optimized, there is enormous potential for improving clinical outcomes for millions of patients. There is substantial scientific and public interest in cardiac regenerative or reparative cell therapy strategies, based on preclinical and early phase 1/2 clinical studies. Although most studies to date have used MSCs isolated from adult tissues, recent evidence indicates that MSCs obtained from the umbilical cord (which is collected after caesarian delivery of a baby) are superior to MSCs from adult tissues, since they are obtained from a much younger organism. Accordingly, we will use umbilical cord-derived MSCs (UC-MSCs). Although cell therapy holds great promise, its development as a widely available clinical option is hindered by the invasive nature of current methods for cell delivery, which require a cardiac catheterization and make it very difficult or impossible to give repeated doses of cells. Giving repeated doses is important because cells disappear rapidly after they are transplanted and thus need to be replaced. To overcome this problem, we will use a less-invasive approach and inject the UC-MSCs by the intravenous route. Our approach is based on recent evidence suggesting that intravenous cell therapy is effective in patients with heart failure and that repeated doses are more effective than a single dose. Accordingly, the proposed clinical trial is a prospective test of these important therapeutic modalities. The study will be a phase 2a, randomized, double-blind, placebo-controlled, multicenter trial that will test whether intravenous injection of UC-MSCs produces beneficial effects in patients with heart failure caused by ICM, and whether four repeated doses have greater therapeutic efficacy than a single dose. The primary outcome will be assessed using cardiac magnetic resonance imaging to measure cardiac function at 12 months after the first treatment. We expect that patients receiving four doses of UC-MSCs will have better heart function than those receiving four doses of placebo, and that the improvement in heart function will be greater after four doses of UC-MSCs than after one dose. This outcome would demonstrate that intravenous delivery of cells is beneficial and that repeated cell doses are superior to a single dose. Such an outcome would have great importance because it would offer a new treatment option (intravenous injection of UC-MSCs) to millions of pati
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310109
Entities
People
- Roberto Bolli
Organizations
- United States Army
- University of Louisville