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Rationale and design of a randomized controlled trial of allogeneic mesenchymal stem cells in patients with nonischemic cardiomyopathy

Greene, Stephen J.; Epstein, Stephen E.; Kim, Raymond J.; Quyyumi, Arshed A.; Cole, Robert T.; Anderson, Allen S.; Wilcox, Jane E.; Skopicki, Hal A.; Sikora, Sergey; Verkh, Lev; Tankovich, Nikolai I.; Gheorghiade, Mihai; Butler, Javed

Journal of Cardiovascular Medicine: April 2017 - Volume 18 - Issue 4 - p 283–290
doi: 10.2459/JCM.0000000000000303
Regenerative medicine

Aims: This article describes an ongoing study investigating the safety and efficacy of ischemia-tolerant mesenchymal stem cell (MSC) therapy in patients with nonischemic heart failure and dysfunctional viable myocardium without scarring. This study will follow principles of the previously described mechanistic translational-phase concept whereby the effect of the study agent on laboratory and imaging markers of cardiac structure and function will be tested in a small homogenous cohort with the goal to enhance the understanding of the effect of interventions on cardiac remodeling and performance.

Study design: This single-blind, placebo-controlled, crossover, multicenter, randomized study will assess the safety, tolerability, and preliminary efficacy of a single intravenous (i.v.) dose of allogeneic ischemia-tolerant MSCs in individuals with heart failure of nonischemic cause, ejection fraction 40% or less, and dysfunctional viable myocardium who have been receiving guideline-directed medical therapy. Eligible patients will have no evidence of baseline replacement scarring on delayed-enhancement cardiac magnetic resonance (CMR). Approximately 20 patients will be randomized in a 1 : 1 ratio to receive an i.v. infusion of ischemia-tolerant MSCs or placebo. At 90 days, the two groups will undergo crossover and received the alternative treatment. The primary endpoint is safety, as evaluated through at least 1-year post-MSC infusion. Additional efficacy endpoints will include measures of cardiac structure and function, as evaluated by serial cine-CMR and transthoracic echocardiography at 90 and 180 days post-initial infusion.

Conclusion: This pilot study will explore the safety and effects on cardiac structure and function of i.v. injection of ischemia-tolerant MSCs in a small homogenous cohort of nonischemic heart failure patients with reduced ejection fraction and absent replacement scarring on CMR. This study also represents a prospective mechanistic translational-phase study using baseline and serial CMR imaging in heart failure patients and serves as a potential model for design of future heart failure trials (ClinicalTrials.gov identifier: NCT02467387).

aDivision of Cardiology, Duke University Medical Center, Durham, North Carolina

bMedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, District of Columbia

cDivision of Cardiology, Emory University, Atlanta, Georgia

dDivision of Cardiology, Northwestern University Feinberg School of Medicine

eDivision of Cardiology, Stony Brook University, Stony Brook, New York

fCardioCell LLC

gStemedica Cell Technologies Inc, San Diego, California

hCenter for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA

Correspondence to Javed Butler, MD, MPH, Division of Cardiology, Stony Brook University, Health Sciences Center, T-16, Room 080, SUNY at Stony Brook, NY 11794, USA Tel: +1 6314441066; fax: +1 6314441054; e-mail: javed.butler@stonybrookmedicine.edu

Received 13 March, 2015

Revised 7 June, 2015

Accepted 12 June, 2015

© 2017 Italian Federation of Cardiology. All rights reserved.