Rationale and design of a randomized controlled trial of allogeneic mesenchymal stem cells in patients with nonischemic cardiomyopathy.
Rationale and design of a randomized controlled trial of allogeneic mesenchymal stem cells in patients with nonischemic cardiomyopathy.
- 2017
Available online through MWHC library: 2006 - present
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. 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). 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.
English
1558-2027
*Cardiomyopathies/su [Surgery]
*Heart Failure/su [Surgery]
*Mesenchymal Stem Cell Transplantation
Cardiomyopathies/dg [Diagnostic Imaging]
Cardiomyopathies/pp [Physiopathology]
Clinical Protocols
Cross-Over Studies
Echocardiography
Heart Failure/dg [Diagnostic Imaging]
Heart Failure/pp [Physiopathology]
Humans
Magnetic Resonance Imaging, Cine
Mesenchymal Stem Cell Transplantation/ae [Adverse Effects]
Myocardium/pa [Pathology]
Pilot Projects
Recovery of Function
Research Design
Single-Blind Method
Stroke Volume
Time Factors
Treatment Outcome
United States
Ventricular Function, Left
Ventricular Remodeling
MedStar Health Research Institute
Journal Article
Available online through MWHC library: 2006 - present
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. 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). 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.
English
1558-2027
*Cardiomyopathies/su [Surgery]
*Heart Failure/su [Surgery]
*Mesenchymal Stem Cell Transplantation
Cardiomyopathies/dg [Diagnostic Imaging]
Cardiomyopathies/pp [Physiopathology]
Clinical Protocols
Cross-Over Studies
Echocardiography
Heart Failure/dg [Diagnostic Imaging]
Heart Failure/pp [Physiopathology]
Humans
Magnetic Resonance Imaging, Cine
Mesenchymal Stem Cell Transplantation/ae [Adverse Effects]
Myocardium/pa [Pathology]
Pilot Projects
Recovery of Function
Research Design
Single-Blind Method
Stroke Volume
Time Factors
Treatment Outcome
United States
Ventricular Function, Left
Ventricular Remodeling
MedStar Health Research Institute
Journal Article