Efficacy and Safety Study of Genetically Targeted Enzyme Replacement Therapy for Advanced Heart Failure (CUPID)

A Phase 1/2 Trial of Intracoronary Administration of MYDICAR® (AAV1/SERCA2a) in Subjects With Heart Failure in Two Stages (Open-Label, Sequential Dose-Escalation Cohorts and Randomized, Double-Blind, Placebo-Controlled, Parallel Cohorts)

The study is divided into 2 parts. In the first part, the safety of the gene transfer agent MYDICAR® will be evaluated. In the second part, the ability of MYDICAR® to improve heart function will be studied.

Study Overview

• Status: Completed
• Conditions: Dilated Cardiomyopathy; Heart Failure, Congestive
• Intervention / Treatment: Genetic: MYDICAR Phase 1 (Open-label, Serial Dose-Escalation Study); Genetic: MYDICAR Phase 2 (Placebo-controlled, Randomized Study); Procedure: Placebo Infusion

Detailed Description

The American Heart Association (AHA) 2006 update on heart disease reported that 5 million Americans are believed to have symptomatic heart failure (HF), and 550,000 patients are newly diagnosed each year. The estimated direct and indirect cost of HF in the United States (U.S.) for 2006 will be ~$29.6 billion. Heart failure is a disabling chronic disease and the most frequent discharge diagnosis for hospitalization among older adults. Despite the significant resources expended on the treatment of this disease, outcomes remain poor. The five-year survival for individuals diagnosed with heart failure is less than 50%, and in end-stage heart failure, the one-year survival may be as low as 25% regardless of medical therapy.

Recent studies suggest that the failing heart is not refractory to treatment, as was previously believed. For example, the observation that a small percentage of subjects with left ventricular assist devices (LVADs) can be permanently weaned from their device strongly suggests that damaged hearts are capable of recovering lost function.

Clinical studies of MYDICAR® have not yet been conducted in humans. Celladon Corporation (Celladon) proposes to investigate gene transfer as a method to restore SERCA2a function in heart failure (HF) patients using a recombinant adeno-associated viral vector (AAV), which consists of an AAV serotype 1 capsid and contains the human SERCA2a complementary DNA (cDNA) flanked by Inverted Terminal Repeats (ITR) derived from AAV serotype 2 (AAV1/SERCA2a). MYDICAR® refers to AAV1/SERCA2a drug product intended for administration by percutaneous delivery.

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92123
      • San Diego Cardiac Center
    • San Diego, California, United States, 92103
      • University of California at San Diego Medical Center
  • Florida
    • Gainesville, Florida, United States, 32608
      • Shands Hospital at University of Florida
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Mid America Heart Institute, Saint Luke's Hospital
    • St. Louis, Missouri, United States, 63110
      • St. Louis University Hospital
  • New Jersey
    • Newark, New Jersey, United States, 07101
      • University of Medicine and Dentistry of New Jersey
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
    • New York, New York, United States, 10032
      • Columbia University Hospital
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center, Presbyterian-Shadyside Hospital
  • Tennessee
    • Tullahoma, Tennessee, United States, 37388
      • Tennessee Center for Clinical Trials & Harton Regional Medical Center
  • Texas
    • Dallas, Texas, United States, 75230
      • Cardiopulmonary Research Science and Technology Institute, Medical City Dallas Hospital
    • Houston, Texas, United States, 77030
      • Methodist Hospital
  • Utah
    • Murray, Utah, United States, 84157
      • Intermountain Medical Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Chronic ischemic or non-ischemic cardiomyopathy. Subjects with ischemic cardiomyopathy must have at least one major coronary vessel with Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow.
• Left ventricular ejection fraction (LVEF) ≤35%
• Diagnosis of New York Heart Association (NYHA) Class III/IV heart failure for a minimum of 3 months prior to screening
• Maximal oxygen consumption (VO2 max) ≤20 mL/kg/min within 90 days prior to enrollment
• An implantable cardioverter defibrillator (ICD) implanted a minimum of 30 days prior to enrollment
• Treatment with appropriate heart failure therapy as tolerated
• All women of childbearing potential must have a negative urine pregnancy test prior to administration of investigational product and agree to use adequate contraception. Men capable of fathering a child must agree to use barrier contraception or limit activity to post-menopausal, surgically sterilized, or a contraception-practicing partner, for 3 months after administration of investigational product.
• Ability to sign Informed Consent Form (ICF) and Release of Medical Information Form

Exclusion Criteria:

• Any intravenous therapy with positive inotropes, vasodilators, or diuretics within 30 days prior to enrollment
• Restrictive cardiomyopathy, obstructive cardiomyopathy, pericardial disease, amyloidosis, infiltrative cardiomyopathy, uncorrected thyroid disease, or dyskinetic LV aneurysm
• Cardiac surgery, percutaneous coronary intervention, or valvuloplasty within 30 days prior to enrollment
• Clinically significant myocardial infarction (e.g., ST elevation MI [STEMI] or large non-STEMI) within 6 months prior to enrollment
• Prior heart transplantation, left ventricular reduction surgery (LVRS), cardiomyoplasty, passive restraint device (e.g., CorCap™ Cardiac Support Device), surgically implanted LVAD or cardiac shunt
• Likely to receive cardiac resynchronization therapy, cardiomyoplasty, LVRS, heart transplant, conventional revascularization procedure, or valvular repair within 6 months following enrollment
• Patients with prior coronary artery bypass graft(s) (CABG) will reviewed on a case-by-case basis
• No evidence of functional or viable myocardium
• Exercise capacity primarily limited by obesity, peripheral vascular disease, intrinsic pulmonary disease or orthopedic problems and not by underlying heart failure
• Known hypersensitivity to octafluoropropane (component of the intravenous echocardiography contrast agent, DEFINITY®) or other contrast dyes used for angiography; history of, or likely need for, high dose steroid pretreatment prior to contrast angiography
• A left ventricle that is difficult to image or high quality echocardiography is not obtainable at screening
• Significant left main or ostial right coronary lumenal stenosis in the opinion of the investigator
• Expected survival <1 year in the investigator's medical opinion
• Suspected or active viral, bacterial, fungal, or parasitic infection within 48 hours prior to enrollment
• Liver function tests (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase) >2x Upper Limit of Normal (ULN) within 30 days prior to enrollment or known intrinsic liver disease (e.g., cirrhosis, chronic hepatitis B or hepatitis C virus infection)
• Current or likely need for hemodialysis within 12 months following enrollment
• Bleeding diathesis or thrombocytopenia defined as platelet count <50,000 platelets/μL
• Anemia defined as hemoglobin <10 g/dL
• Known AIDS or HIV-positive status, or a previous diagnosis of immunodeficiency with an absolute neutrophil count <1000 cells/mm3
• Previous participation in a study of gene transfer
• Presence of neutralizing anti-AAV1 antibodies at titer ≥1:2 within 3 months of screening
• Receiving investigational intervention or participating in another clinical study within 30 days or within 5 half-lives of the investigational drug administration prior to enrollment
• Pregnancy or lactation
• Recent history of psychiatric disease (including drug or alcohol abuse) that is likely to impair subject's ability to comply with protocol-mandated procedures, in the opinion of the investigator
• Other concurrent medical condition(s) that, while not explicitly excluded by the protocol, could jeopardize the safety of the patient or objectives of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MYDICAR Very Low Dose; Single dose of MYDICAR, a viral vector (adeno-associated virus serotype 1 [AAV1]) carrying the gene for sarcoplasmic reticulum Ca++-adenosine triphosphatase (SERCA2a), at a dose of 1.4x10e11 DNAase resistant particles administered by antegrade epicardial coronary artery infusion. Used in MYDICAR Phase 1 (Open-label, Serial Dose-Escalation Study) only.	Genetic: MYDICAR Phase 1 (Open-label, Serial Dose-Escalation Study); MYDICAR administered by antegrade epicardial coronary artery infusion; Other Names: AAV1/SERCA2a
Experimental: MYDICAR Low Dose; Single dose of MYDICAR, a viral vector (adeno-associated virus serotype 1 [AAV1]) carrying the gene for sarcoplasmic reticulum Ca++-adenosine triphosphatase (SERCA2a), at a dose of 6x10e11 DNAase resistant particles administered by antegrade epicardial coronary artery infusion. Used in MYDICAR Phase 1 (Open-label, Serial Dose-Escalation Study) and MYDICAR Phase 2 (Placebo-controlled, Randomized Study)	Genetic: MYDICAR Phase 1 (Open-label, Serial Dose-Escalation Study); MYDICAR administered by antegrade epicardial coronary artery infusion; Other Names: AAV1/SERCA2a; Genetic: MYDICAR Phase 2 (Placebo-controlled, Randomized Study); MYDICAR administered by antegrade epicardial coronary artery infusion; Other Names: AAV1/SERCA2a
Experimental: MYDICAR Mid Dose; Single dose of MYDICAR, a viral vector (adeno-associated virus serotype 1 [AAV1]) carrying the gene for sarcoplasmic reticulum Ca++-adenosine triphosphatase (SERCA2a), at a dose of 3x10e12 DNAase resistant particles administered by antegrade epicardial coronary artery infusion. Used in MYDICAR Phase 1 (Open-label, Serial Dose-Escalation Study) and MYDICAR Phase 2 (Placebo-controlled, Randomized Study).	Genetic: MYDICAR Phase 1 (Open-label, Serial Dose-Escalation Study); MYDICAR administered by antegrade epicardial coronary artery infusion; Other Names: AAV1/SERCA2a; Genetic: MYDICAR Phase 2 (Placebo-controlled, Randomized Study); MYDICAR administered by antegrade epicardial coronary artery infusion; Other Names: AAV1/SERCA2a
Experimental: MYDICAR High Dose; Single dose of MYDICAR, a viral vector (adeno-associated virus serotype 1 [AAV1]) carrying the gene for sarcoplasmic reticulum Ca++-adenosine triphosphatase (SERCA2a), at a dose of 1x10e13 DNAase resistant particles administered by antegrade epicardial coronary artery infusion. Used in MYDICAR Phase 1 (Open-label, Serial Dose-Escalation Study) and MYDICAR Phase 2 (Placebo-controlled, Randomized Study).	Genetic: MYDICAR Phase 1 (Open-label, Serial Dose-Escalation Study); MYDICAR administered by antegrade epicardial coronary artery infusion; Other Names: AAV1/SERCA2a; Genetic: MYDICAR Phase 2 (Placebo-controlled, Randomized Study); MYDICAR administered by antegrade epicardial coronary artery infusion; Other Names: AAV1/SERCA2a
Placebo Comparator: Placebo infusion; A single dose of placebo (Sodium Chloride Injection, USP) administered by antegrade epicardial coronary artery infusion.	Procedure: Placebo Infusion; Saline; epicardial coronary artery infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 2: Incidence of Treatment-emergent Adverse Events (TEAE) at 12 Months	Includes all adverse events that occurred from the time of first infusion of the investigational product or placebo to the 12-month visit. The category of "TEAEs related to the investigational product (IP)" includes TEAEs considered by the investigator to be possibly, probably, or definitely related to the IP.	12 months
Phase 2: Length of Cardiovascular-related Hospitalizations at 6 Months	Mean number of days in the hospital for cardiovascular-related complications. All hospitalizations were evaluated and classified by the blinded Clinical Endpoints Committee.	6 months
Phase 2: Change in Symptomatic Efficacy Domains From Baseline to Month 6: New York Heart Association (NYHA) Class and Minnesota Living With Heart Failure Questionnaire (MLWHFQ) Score	NYHA classification is a symptomatic assessment in which the investigator evaluates subjects on a scale ranging from Class I (subjects with no limitation of activities, no symptoms from ordinary activities) to Class IV (subjects who should be at complete rest, confined to bed or chair; any physical activity brings on discomfort and symptoms occur at rest). The MLWHFQ is a patient-reported quality of life (QoL) measure in which patients assess the impact of their heart condition on activities in the past month using a Likert scale ranging from 0 (no effect) to 5 (very much effect). Higher scores thus indicate a lower QoL. The maximum (worst) score is 105 and the minimum (best) score is 0. For both measures, changes from baseline with positive values indicate a worsening in symptoms and changes from baseline with negative values indicate an improvement in symptoms.	Baseline to 6 months
Phase 2: Change in 6-minute Walk Test (6MWT) From Baseline to Month 6	The 6MWT measures the distance walked in meters during a 6-minute test. Higher values indicate a better functional status. Changes from baseline with negative values indicate a worsening in function and changes from baseline with positive values indicate an improvement in function.	Baseline to 6 months
Phase 2: Change in Peak Maximum Oxygen Consumption (VO2) From Baseline to Month 6	Peak VO2 is a measure of maximal oxygen consumption during cardiopulmonary exercise testing; this study used the modified Naughton treadmill protocol. Higher values indicate a better functional status. Changes from baseline with negative values indicate a worsening in function and changes from baseline with positive values indicate an improvement in function.	Baseline to 6 months
Phase 2: Change in Absolute Levels of N-terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) From Baseline to Month 6	NT-proBNP is a biomarker for heart failure. Increased levels of this biomarker are associated with increased mortality and cardiovascular hospitalization in patients with heart failure.	Baseline to 6 months
Phase 2: Change in Percentage of Blood Ejected From the Left Ventricle (LV) (i.e., Left Ventricular Ejection Fraction [LVEF]) From Baseline to Month 6	Contrast echocardiography was used to determine LVEF. Increases in LVEF are associated with reduced mortality. Changes from baseline with positive values indicate an improvement in heart function and changes from baseline with negative values indicate a worsening of heart function.	Baseline to 6 months
Phase 2: Change in Absolute Left Ventricular End Systolic Volume (LVESV) Frm Baseline to Month 6	Contrast echocardiography was used to determine LVESV. Decreases in LVESV are associated with reduced mortality. Changes from baseline with positive values indicate a worsening in heart function and changes from baseline with negative values indicate an improvement in symptoms.	Baseline to 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 2: Length of Cardiovascular-related Hospitalizations at 12 Months	Mean number of days in the hospital for cardiovascular-related complications. All hospitalizations were evaluated and classified by the blinded Clinical Endpoints Committee.	12 months
Phase 2: Change in Symptomatic Efficacy Domains From Baseline to Month 12: New York Heart Association (NYHA) Class and Minnesota Living With Heart Failure Questionnaire (MLWHFQ) Score	NYHA classification is a symptomatic assessment in which the investigator evaluates subjects on a scale ranging from Class I (subjects with no limitation of activities, no symptoms from ordinary activities) to Class IV (subjects who should be at complete rest, confined to bed or chair; any physical activity brings on discomfort and symptoms occur at rest). The MLWHFQ is a patient-reported quality of life (QoL) measure in which patients assess the impact of their heart condition on activities in the past month using a Likert scale ranging from 0 (no effect) to 5 (very much effect). Higher scores thus indicate a lower QoL. The maximum (worst) score is 105 and the minimum (best) score is 0. For both measures, changes from baseline with positive values indicate a worsening in symptoms and changes from baseline with negative values indicate an improvement in symptoms.	Baseline to 12 months
Phase 2: Change in 6-minute Walk Test (6MWT) From Baseline to Month 12	The 6MWT measures the distance walked in meters during a 6-minute test. Higher values indicate a better functional status. Changes from baseline with negative values indicate a worsening in function and changes from baseline with positive values indicate an improvement in function.	Baseline to 12 months
Phase 2: Change in Peak Maximum Oxygen Consumption (VO2) From Baseline to Month 12	Peak VO2 is a measure of maximal oxygen consumption during cardiopulmonary exercise testing; this study used the modified Naughton treadmill protocol. Higher values indicate a better functional status. Changes from baseline with negative values indicate a worsening in function and changes from baseline with positive values indicate an improvement in function.	Baseline to 12 months
Phase 2: Change in Absolute Levels of N-terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) From Baseline to Month 12	NT-proBNP is a biomarker for heart failure. Increased levels of this biomarker are associated with increased mortality and cardiovascular hospitalization in patients with heart failure.	Baseline to 12 months
Phase 2: Change in Percentage of Blood Ejected From the Left Ventricle (LV) (i.e., Left Ventricular Ejection Fraction [LVEF]) From Baseline to Month 12	Contrast echocardiography was used to determine LVEF. Increases in LVEF are associated with reduced mortality. Changes from baseline with positive values indicate an improvement in heart function and changes from baseline with negative values indicate a worsening of heart function.	Baseline to 12 months
Phase 2: Change in Absolute Left Ventricular End Systolic Volume (LVESV) From Baseline to Month 12	Contrast echocardiography was used to determine LVESV. Decreases in LVESV are associated with reduced mortality. Changes from baseline with positive values indicate a worsening in heart function and changes from baseline with negative values indicate an improvement in symptoms.	Baseline to 12 months
Phase 1 and Phase 2: All Subject Deaths Through 36 Months	All subject deaths that occurred during the 12-month study or the 24-month follow-up in subjects enrolled in either the Phase 1 or Phase 2 trial. Events occurring after early termination from the trial are listed as occurring during long-term follow-up, but may have been within 12 months. Specifically, two cardiovascular (CV) deaths in placebo subjects occurred following early study termination, but within 12 months of study initiation. These deaths are therefore included under "Deaths within 12 months" but also listed as "Cardiovascular deaths in long-term follow-up." Accordingly, the number of "Cardiovascular deaths in long-term follow-up" for the placebo group is greater than the number of "Deaths after 12 months," as 2 of the deaths occurred within 12 months but after early termination.	36 months

Collaborators and Investigators

• Sponsor: Celladon Corporation
• Investigators: Principal Investigator: Randall Starling, MD, The Cleveland Clinic; Principal Investigator: Thomas Cappola, MD, ScM, University of Pennsylvania; Principal Investigator: Brian Jaski, MD, San Diego Cardiac Center; Principal Investigator: Stephen Archer, MD, University of Chicago; Principal Investigator: Donna Mancini, MD, Columbia University Hospital; Study Chair: Mariell Jessup, MD, University of Pennsylvania; Principal Investigator: Daniel Pauly, MD, Shands Hospital, University of Florida at Gainesville; Principal Investigator: Barry London, MD, University of Pittsburgh Medical Center; Principal Investigator: Barry Greenberg, MD, University of California at San Diego Medical Center; Principal Investigator: A. G. Kfoury, MD, Intermountain Medical Center; Principal Investigator: Andrew Kao, MD, Mid America Heart Institute, Saint Luke's Hospital; Principal Investigator: Paul J. Hauptman, MD, St. Louis University Hospital; Principal Investigator: Jill Kalman, MD, Icahn School of Medicine at Mount Sinai; Principal Investigator: Douglas W. Losordo, MD, Northwestern University; Principal Investigator: Eric J. Eichhorn, MD, FACC, Cardiopulmonary Research Science and Technology Institutte, Medical City Dallas Hospital; Principal Investigator: Stephanie H. Dunlap, DO, University of Cincinnati; Principal Investigator: Vinay Thohan, MD, Wake Forest University; Principal Investigator: Maryl R. Johnson, MD, University of Wisconsin, Madison; Principal Investigator: Mark Dunlap, MD, MetroHealth Medical Center; Principal Investigator: Joaquin E. Cigarroa, MD, Oregon Health and Science University; Principal Investigator: Dinesh K. Gupta, MD, Tennessee Center for Clinical Trials, Harton Regional Medical Center; Principal Investigator: Marc Klapholz, MD, University of Medicine and Dentistry of New Jersey; Principal Investigator: Guillermo Torre, MD, The Methodist Hospital Research Institute

Publications and helpful links

General Publications

• Horowitz JD, Rosenson RS, McMurray JJ, Marx N, Remme WJ. Clinical Trials Update AHA Congress 2010. Cardiovasc Drugs Ther. 2011 Feb;25(1):69-76. doi: 10.1007/s10557-011-6285-9.
• Hajjar RJ, Zsebo K, Deckelbaum L, Thompson C, Rudy J, Yaroshinsky A, Ly H, Kawase Y, Wagner K, Borow K, Jaski B, London B, Greenberg B, Pauly DF, Patten R, Starling R, Mancini D, Jessup M. Design of a phase 1/2 trial of intracoronary administration of AAV1/SERCA2a in patients with heart failure. J Card Fail. 2008 Jun;14(5):355-67. doi: 10.1016/j.cardfail.2008.02.005. Epub 2008 May 27.
• Jaski BE, Jessup ML, Mancini DM, Cappola TP, Pauly DF, Greenberg B, Borow K, Dittrich H, Zsebo KM, Hajjar RJ; Calcium Up-Regulation by Percutaneous Administration of Gene Therapy In Cardiac Disease (CUPID) Trial Investigators. Calcium upregulation by percutaneous administration of gene therapy in cardiac disease (CUPID Trial), a first-in-human phase 1/2 clinical trial. J Card Fail. 2009 Apr;15(3):171-81. doi: 10.1016/j.cardfail.2009.01.013.
• Jessup M, Greenberg B, Mancini D, Cappola T, Pauly DF, Jaski B, Yaroshinsky A, Zsebo KM, Dittrich H, Hajjar RJ; Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID) Investigators. Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID): a phase 2 trial of intracoronary gene therapy of sarcoplasmic reticulum Ca2+-ATPase in patients with advanced heart failure. Circulation. 2011 Jul 19;124(3):304-13. doi: 10.1161/CIRCULATIONAHA.111.022889. Epub 2011 Jun 27.
• Zsebo K, Yaroshinsky A, Rudy JJ, Wagner K, Greenberg B, Jessup M, Hajjar RJ. Long-term effects of AAV1/SERCA2a gene transfer in patients with severe heart failure: analysis of recurrent cardiovascular events and mortality. Circ Res. 2014 Jan 3;114(1):101-8. doi: 10.1161/CIRCRESAHA.113.302421. Epub 2013 Sep 24.

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Primary Completion (Actual): August 1, 2010
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: March 30, 2007
• First Submitted That Met QC Criteria: March 30, 2007
• First Posted (Estimate): April 2, 2007

Study Record Updates

• Last Update Posted (Estimate): August 20, 2014
• Last Update Submitted That Met QC Criteria: August 19, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Cardiomegaly; Laminopathies; Heart Failure; Cardiomyopathies; Cardiomyopathy, Dilated
• Other Study ID Numbers: CELL-001; CUPID Trial (Registry Identifier: NCT00454818)