Intravenous Allogeneic Mesenchymal Stem Cells for Non-Ischemic Cardiomyopathy: Safety and Efficacy Results of a Phase II-A Randomized Trial
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 (1.5x106 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 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.
- Received August 3, 2016.
- Revision received October 23, 2016.
- Accepted November 11, 2016.