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

Abstract

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).

• Authors: Stephen J Greene, Stephen E Epstein, Raymond J Kim, Arshed A Quyyumi, Robert T Cole, Allen S Anderson, Jane E Wilcox, Hal A Skopicki, Sergey Sikora, Lev Verkh, Nikolai I Tankovich, Mihai Gheorghiade, Javed Butler
• Journal: Journal of cardiovascular medicine (Hagerstown, Md.) (J Cardiovasc Med (Hagerstown)) Vol. 18 Issue 4 Pg. 283-290 (Apr 2017) ISSN: 1558-2035 [Electronic] United States
• PMID: 26479144 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial)

Topics

• Cardiomyopathies (diagnostic imaging, physiopathology, surgery)
• Clinical Protocols
• Cross-Over Studies
• Echocardiography
• Heart Failure (diagnostic imaging, physiopathology, surgery)
• Humans
• Magnetic Resonance Imaging, Cine
• Mesenchymal Stem Cell Transplantation (adverse effects)
• Myocardium (pathology)
• Pilot Projects
• Recovery of Function
• Research Design
• Single-Blind Method
• Stroke Volume
• Time Factors
• Treatment Outcome
• United States
• Ventricular Function, Left
• Ventricular Remodeling