Wednesday, October 21, 2015
Journal of Cardiovascular Medicine
Rational and Design of a Randomized Controlled Trial of Allogeneic Mesenchymal Stem Cells in Patients With Non-ischemic Cardiomyopathy
Details from CardioCell’s Phase IIa chronic heart failure clinical trial are featured in a peer-reviewed article now available in the Journal of Cardiovascular Medicine. Entitled “Rational and Design of a Randomized Controlled Trial of Allogeneic Mesenchymal Stem Cells in Patients With Non-ischemic Cardiomyopathy,” 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 CardioCell’s chronic heart failure clinical trial (NCT02123706) principal investigators Drs. Allen S. Anderson, Robert T. Cole and Hal A. Skopicki, clinical trial coordinator Jane E. Wilcox and MRI image analyst Dr. Raymond J. Kim.
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
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).