Rationale and design of the first randomized, double-blind, placebo-controlled trial of intramyocardial injection of autologous bone-marrow derived Mesenchymal Stromal Cells in chronic ischemic Heart Failure (MSC-HF Trial)

doi:10.1016/j.ahj.2012.05.026

American Heart Journal

Volume 164, Issue 3, September 2012, Pages 285-291

https://doi.org/10.1016/j.ahj.2012.05.026 Get rights and content

Background

Stem cell therapy is an emerging treatment modality in cardiovascular disease. The best cell type and delivery method in different cardiovascular diseases remain to be determined.

Study Design

The MSC-HF trial is a phase 2, single-center, double-blind, randomized, placebo-controlled trial of intramyocardial delivery of autologous bone-marrow derived mesenchymal stromal cells (MSCs) in patients with chronic ischemic heart failure. A total of 60 patients will be randomized in a 2:1 pattern to receive intramyocardial injections of either MSCs or placebo. Patients will be followed up for 12 months.

Methods

Bone marrow will be obtained by aspiration from the iliac crest. Mesenchymal stromal cells will be isolated, and culture will be expanded for 6 to 8 weeks. A total of 12 to 15 MSC or placebo injections will be placed in an ischemic viable region of the myocardium using the electromechanical NOGA-XP system (Biologics Delivery Systems Group, Johnson & Johnson, Irwindale, CA).

Endpoints

The primary endpoint is change in left ventricle end-systolic volume, measured by magnetic resonance imaging (MRI) or computed tomography (CT) at 6-month follow-up. Secondary endpoints are left ventricle ejection fraction, ventricular volumes, wall thickness, and systolic wall thickening measured by MRI or CT in addition to measurement of myocardial scar tissue by MRI. Other secondary endpoints are safety of treatment, clinical symptoms and functional capacity, weekly angina attacks, use of short-term nitroglycerine, and quality of life.

Conclusion

A randomized, double-blind, placebo-controlled, clinical trial of intramyocardial delivery of MSCs in patients with ischemic heart failure has been set up to confirm the positive findings in open-labeled clinical trials.

Section snippets

Background

Despite advances in treatment of coronary artery disease (CAD) with stabilizing drugs and mechanical revascularization, many patients cannot be treated successfully with these conventional therapies and consequently suffer from refractory angina and post infarction heart failure. After heart failure diagnosis has been established, approximately 20% of patients die within the first year, and 50% die within 5 years.¹

Therapy with stem cells with potential to regenerate damaged myocardium is an

Study objectives

The primary objective of the MSC-HF trial is to evaluate efficacy of intramyocardial injection of autologous BM MSCs in patients with chronic CAD and heart failure in a double-blind, randomized, placebo-controlled setting.

Study overview

This study is a phase 2, single-center, double-blind, randomized, placebo-controlled trial. The study protocol complies with the declaration of Helsinki and was approved by The Danish National Committee on Biomedical Research Ethics (j.nr: H-A-2008-043) and Danish Medicines

Discussion

The present study is the first double-blind, randomized, placebo-controlled trial of intramyocardial injection of autologous BM-derived MSCs in patients with chronic ischemic heart failure. Considerations regarding cell type and delivery method in this trial are based on previous preclinical studies and clinical trials on cell therapy for different cardiovascular diseases.²

The optimal therapeutic cell type is likely to differ between different cardiovascular diseases. For patients with acute

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Trial DesignRationale and design of the first randomized, double-blind, placebo-controlled trial of intramyocardial injection of autologous bone-marrow derived Mesenchymal Stromal Cells in chronic ischemic Heart Failure (MSC-HF Trial)

Background

Study Design

Methods

Endpoints

Conclusion

Section snippets

Background

Study objectives

Study overview

Discussion

Am J Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Am J Cardiol

JACC Cardiovasc Interv

Cytotherapy

J Am Coll Cardiol

Mech Ageing Dev

J Mol Cell Cardiol

Trends in heart failure incidence and survival in a community-based population

JAMA

Mesenchymal stromal cells for cardiovascular repair: current status and future challenges

Future Cardiol

Comparison of different culture conditions for human mesenchymal stromal cells for clinical stem cell therapy

Scand J Clin Lab Invest

Transcoronary transplantation of autologous mesenchymal stem cells and endothelial progenitors into infarcted human myocardium

Catheter Cardiovasc Interv

Intracoronary transplantation of autologous bone marrow mesenchymal stem cells for ischemic cardiomyopathy due to isolated chronic occluded left anterior descending artery

J Invasive Cardiol

Electrophysiological effects of intracoronary transplantation of autologous mesenchymal and endothelial progenitor cells

Europace

Mesenchymal stromal cell derived endothelial progenitor treatment in patients with refractory angina

Scand Cardiovasc J

Direct intramyocardial mesenchymal stromal cell injections in patients with severe refractory angina—one year follow-up

Cell Transplant

Trial Design
Rationale and design of the first randomized, double-blind, placebo-controlled trial of intramyocardial injection of autologous bone-marrow derived Mesenchymal Stromal Cells in chronic ischemic Heart Failure (MSC-HF Trial)