TY - BOOK AU - Epstein, Stephen E AU - Lipinski, Michael J TI - Intravenous Allogeneic Mesenchymal Stem Cells for Nonischemic Cardiomyopathy: Safety and Efficacy Results of a Phase II-A Randomized Trial SN - 0009-7330 PY - 2017/// KW - *Cardiomyopathies/di [Diagnosis] KW - *Cardiomyopathies/th [Therapy] KW - *Health Status KW - *Mesenchymal Stem Cell Transplantation/mt [Methods] KW - Adult KW - Cardiomyopathies/bl [Blood] KW - Cross-Over Studies KW - Female KW - Humans KW - Infusions, Intravenous KW - Male KW - Middle Aged KW - Pilot Projects KW - Recovery of Function/ph [Physiology] KW - Single-Blind Method KW - Transplantation, Homologous/mt [Methods] KW - Treatment Outcome KW - MedStar Health Research Institute KW - MedStar Heart & Vascular Institute KW - Journal Article N1 - Available online from MWHC library: 1953 - present N2 - CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02467387; CONCLUSIONS: In this pilot study of patients with nonischemic cardiomyopathy, itMSC therapy was safe, caused immunomodulatory effects, and was associated with improvements in health status and functional capacity; Copyright 2016 American Heart Association, Inc; METHODS AND RESULTS: This was a single-blind, placebo-controlled, crossover, randomized phase II-a trial of nonischemic cardiomyopathy patients with left ventricular ejection fraction <40% and absent hyperenhancement on cardiac magnetic resonance imaging. Patients were randomized to intravenously administered itMSCs (1.5x106 cells/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 2 treatments. Change from baseline in left ventricular ejection fraction and ventricular volumes was not significantly different between therapies. Compared with placebo, itMSC therapy increased 6-minute walk distance (+36.47 m, 95% confidence interval 5.98-66.97; P=0.02) and improved Kansas City Cardiomyopathy clinical summary (+5.22, 95% confidence interval 0.70-9.74; P=0.02) and functional status scores (+5.65, 95% confidence interval -0.11 to 11.41; P=0.06). The data demonstrated MSC-induced immunomodulatory effects, the magnitude of which correlated with improvement in left ventricular ejection fraction; OBJECTIVE: To assess the safety and preliminary efficacy of intravenously administered ischemia-tolerant MSCs (itMSCs) in patients with nonischemic cardiomyopathy; RATIONALE: Potential benefits of mesenchymal stem cell (MSC) therapy in heart failure 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 heart failure, an entity in which excessive chronic inflammation may play a pivotal role UR - https://dx.doi.org/10.1161/CIRCRESAHA.116.309717 ER -