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Wednesday, November 16, 2016

Circulation Research, a Journal of the American Heart Association

Intravenous Allogeneic Mesenchymal Stem Cells for Non-Ischemic Cardiomyopathy: Safety and Efficacy Results of a Phase II-A Randomized Trial

Results from CardioCell’s Phase IIa chronic heart failure clinical trial are featured in a peer-reviewed article now available in the American Heart Association’s journal Circulation Research. Entitled “Intravenous Allogeneic Mesenchymal Stem Cells for Non-Ischemic Cardiomyopathy: Safety and Efficacy Results of a Phase II-A Randomized Trial,” the paper authors include CardioCell’s Scientific Advisory Board members Drs. Stephen E. Epstein, Arshed A. Quyyumi, Mihai Gheorghiade and Javed Butler, as well as board directors Sergey Sikora, Ph.D., and Nikolai I. Tankovich, M.D., Ph.D. Additional authors include Stephen J. Greene,  Raymond J. Kim, Allen S. Anderson, Jane E. Wilcox, Michael J. Lipinski, Yi-an Ko, Kenneth B. Margulies, Robert T. Cole and Hal A. Skopicki.

The full article is available online via subscription or for purchase at Circulation Research, or contact CardioCell for more detail.

Abstract

Intravenous Allogeneic Mesenchymal Stem Cells for Non-Ischemic Cardiomyopathy: Safety and Efficacy Results of a Phase II-A Randomized Trial

Authors: Javed Butler, Stephen E. Epstein, Stephen J. Greene, Arshed A. Quyyumi, Sergey Sikora, Raymond J. Kim, Allen S. Anderson, Jane E. Wilcox, Nikolai I. Tankovich, Michael J. Lipinski, Yi-an Ko, Kenneth B. Margulies, Robert T. Cole, Hal A. Skopicki and Mihai Gheorghiade

Rationale: Potential benefits of mesenchymal stem cell (MSC) therapy in heart failure (HF) may be related to paracrine properties and systemic effects, including anti-inflammatory activities. If this hypothesis is valid, intravenous administration of MSCs should improve outcomes in HF, an entity in which excessive chronic inflammation may play a pivotal role.

Objective: To assess the safety and preliminary efficacy of intravenously administered ischemia tolerant MSCs (itMSCs) in patients with non-ischemic cardiomyopathy.

Methods and Results: This is a single-blind, placebo-controlled, crossover, randomized phase II-a trial of non-ischemic cardiomyopathy patients with left ventricular ejection fraction (LVEF) ≤40% and absent hyper-enhancement on cardiac magnetic resonance (CMR) imaging. Patients were randomized to intravenously administered itMSCs (1.5×106cells/kg) or placebo; at 90 days each group received the alternative treatment. Overall, 22 patients were randomized to itMSC (n=10) and placebo (n=12) at baseline. After crossover, data were available for 22 itMSC patients. No major differences in death, hospitalization, or serious adverse events were noted between the two treatments. Change from baseline in LVEF and ventricular volumes were not significantly different between therapies. Compared to placebo, itMSC therapy increased 6-minute walk distance (+36.47m, 95%CI 5.98-66.97, p=0.02), and improved Kansas City Cardiomyopathy clinical summary (+5.22, 95%CI 0.70-9.74, p=0.02) and functional status scores (+5.65, 95%CI -0.11-11.41, p=0.06). Data demonstrated MSC-induced immunomodulatory effects, the magnitude of which correlated with improvement in LVEF.

Conclusions: In this pilot study of patients with non-ischemic cardiomyopathy, itMSC therapy was safe, caused immunomodulatory effects, and associated with improvements in health status and functional capacity. ClinicalTrials.gov identifier: NCT02467387.