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Combination of Mesenchymal and C-kit+ Cardiac Stem Cells as Regenerative Therapy for Heart Failure (CONCERT-HF)

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ClinicalTrials.gov Identifier: NCT02501811
Recruitment Status : Recruiting
First Posted : July 17, 2015
Last Update Posted : May 17, 2018
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Dr Lemuel A Moye III, The University of Texas Health Science Center, Houston

Brief Summary:
This is a phase II, randomized, placebo-controlled clinical trial designed to assess feasibility, safety, and effect of autologous bone marrow-derived mesenchymal stem cells (MSCs) and c-kit+ cardiac stem cells (CSCs) both alone and in combination (Combo), compared to placebo (cell-free Plasmalyte-A medium) as well as each other, administered by transendocardial injection in subjects with ischemic cardiomyopathy.

Condition or disease Intervention/treatment Phase
Ischemic Cardiomyopathy Biological: Mesenchymal Stem Cells (MSC) Biological: Cardiac Stem Cells (CSC) Biological: Placebo (Plasmalyte A) Phase 2

Detailed Description:
This is a randomized, placebo-controlled clinical trial designed to evaluate the feasibility, safety, and effect of Combo, MSCs alone, and CSCs alone compared with placebo as well as each other in subjects with heart failure of ischemic etiology. Following a successful lead-in phase, a total of one hundred forty-four (144) subjects will be randomized (1:1:1:1) to receive Combo, MSCs, CSCs, or placebo. After randomization, baseline imaging, relevant harvest procedures, and study product injection, subjects will be followed up at 1 day, 1 week, 1 month, 3 months, 6 months and 12 months post study product injection. All subjects will receive study product injection (cells or placebo) using the NOGA® XP Mapping and Navigation System. Subjects will have delayed-enhanced magnetic resonance imaging (DEMRI) scans to assess scar size and LV function and structure at baseline and at 6 and 12 months post study product administration. All endpoints will be assessed at the 6 and 12 month visits which will occur 180 ±30 days and 365 ±30 days respectively from the day of study product injection (Day 0). For the purpose of the endpoint analysis and safety evaluations, the Investigators will utilize an "intention-to-treat" study population, however an as treated analysis will also be conducted.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 144 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase II, Randomized, Placebo-Controlled Study of the Safety, Feasibility, and Efficacy of Autologous Mesenchymal Stem Cells and C-kit+ Cardiac Stem Cells, Alone or in Combination, Administered Transendocardially in Subjects With Ischemic Heart Failure
Study Start Date : October 2015
Estimated Primary Completion Date : November 2019
Estimated Study Completion Date : May 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Mesenchymal Stem Cells (MSC)
Target dose of 150 million MSCs
Biological: Mesenchymal Stem Cells (MSC)
15 transendocardial injections of 0.4ml MSCs administered to the left ventricle via NOGA Myostar injection catheter (single procedure)

Experimental: Cardiac Stem Cells (CSC)
Target dose of 5 million CSCs
Biological: Cardiac Stem Cells (CSC)
15 transendocardial injections of 0.4ml CSCs administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
Other Name: c-kit+ cells

Experimental: MSC+CSC Combination Cells (Combo)
Target dose of 150 million MSCs and 5 million CSCs
Biological: Mesenchymal Stem Cells (MSC)
15 transendocardial injections of 0.4ml MSCs administered to the left ventricle via NOGA Myostar injection catheter (single procedure)

Biological: Cardiac Stem Cells (CSC)
15 transendocardial injections of 0.4ml CSCs administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
Other Name: c-kit+ cells

Placebo Comparator: Placebo (Plasmalyte A)
Plasmalyte A
Biological: Placebo (Plasmalyte A)
15 transendocardial injections of 0.4ml placebo administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
Other Name: Plasmalyte A




Primary Outcome Measures :
  1. Change in Left Ventricular Ejection Fraction (LVEF) as measured by cMRI [ Time Frame: Baseline to 6 months ]
  2. Change in Global Strain (HARP MRI) as measured by cMRI [ Time Frame: Baseline to 6 months ]
  3. Change in Regional Strain (HARP MRI) as measured by cMRI [ Time Frame: Baseline to 6months ]
  4. Change in Left Ventricular End Diastolic Volume Index (LVEDVI) as measured by cMRI [ Time Frame: Baseline to 6 months ]
  5. Change in Left Ventricular End Systolic Volume Index (LVESVI) as measured by cMRI [ Time Frame: Baseline to 6 months ]
  6. Change in Left Ventricular Sphericity Index as measured by cMRI [ Time Frame: Baseline to 6 months ]
  7. Change in Infarct/scar Volume (DEMRI) as measured by cMRI [ Time Frame: Baseline to 6 months ]
  8. Change in Maximal Oxygen Consumption (VO2 max) as measured by treadmill [ Time Frame: Baseline to 6 months ]
  9. Change in Exercise Tolerance as measured by the six minute walk test [ Time Frame: Baseline to 6 months ]
  10. Change in Minnesota Living with Heart Failure Questionnaire (MHLFQ) Score [ Time Frame: Baseline to 6 months ]
  11. Cumulative Days alive and out of hospital for heart failure [ Time Frame: Baseline to 6 months ]
  12. Change in N-Terminal pro-Brain Natriuretic Peptide (NT-proBNP) as measured by blood draw [ Time Frame: Baseline to 6 months ]
  13. Incidence rate of Death [ Time Frame: Baseline to 6 months ]
  14. Incidence rate of Hospitalization for Heart Failure [ Time Frame: Baseline to 6 months ]
  15. Incidence rate of Heart Failure Exacerbation (Non hospitalization) [ Time Frame: Baseline to 6 months ]


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Ages Eligible for Study:   21 Years to 79 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Be ≥ 21 and <80 years of age
  2. Have documented coronary artery disease (CAD) with evidence of myocardial injury, LV dysfunction, and clinical evidence of HF
  3. Have a "detectable" area of myocardial injury defined as ≥ 5% LV involvement (infarct volume) and any subendocardial involvement by cMRI
  4. Have an EF ≤ 40% by cMRI
  5. Be receiving guideline‐driven medical therapy for heart failure at stable and tolerated doses for ≥ 1 month prior to consent. For beta‐blockade "stable" is defined as no greater than a 50% reduction in dose or no more than a 100% increase in dose.
  6. Be a candidate for cardiac catheterization
  7. Have NYHA class I, II, or III heart failure symptoms
  8. If a female of childbearing potential, be willing to use one form of birth control for the duration of the study, and undergo a pregnancy test at baseline and within 36 hours prior to injection

Exclusion Criteria:

  1. Indication for standard-of-care surgery (including valve surgery, placement of left-ventricular assist device, or imminent heart transplantation), coronary artery bypass grafting (CABG) procedure, and/or percutaneous coronary intervention (PCI) for the treatment of ischemic and/or valvular heart disease. Subjects who require or undergo PCI should undergo these procedures a minimum of 3 months in advance of randomization. Subjects who require or undergo CABG should undergo these procedures a minimum of 4 months in advance of randomization. In addition, subjects who develop a need for revascularization following enrollment should undergo revascularization without delay. Indication for imminent heart transplantation is defined as a high likelihood of transplant prior to collection of the 12 month study endpoint. Candidates cannot be UNOS status 1A or 1B, and they must have documented low probability of being transplanted
  2. Valvular heart disease including 1) mechanical or bioprosthetic heart valve; or 2) severe (any valve) insufficiency/regurgitation within 12 months of consent
  3. Aortic stenosis with valve area ≤ 1.5 cm2
  4. History of ischemic or hemorrhagic stroke within 90 days of consent
  5. History of a left ventricular remodeling surgical procedure utilizing prosthetic material
  6. Presence of a pacemaker and/or implantable cardioverter-defibrillator (ICD) generator with any of the following limitations/conditions:

    • manufactured before the year 2000
    • leads implanted < 6 weeks prior to consent
    • non-transvenous epicardial, or abandoned leads
    • subcutaneous ICDs
    • leadless pacemakers
    • any other condition that, in the judgment of device-trained staff, would deem an MRI contraindicated
  7. Pacemaker-dependence with an ICD (Note: pacemaker-dependent candidates without an ICD are not excluded)
  8. A cardiac resynchronization therapy (CRT) device implanted less than 3 months prior to consent
  9. Other MRI contraindications (e.g. patient body habitus incompatible with MRI)
  10. An appropriate ICD firing or anti-tachycardia pacing (ATP) for ventricular fibrillation or ventricular tachycardia within 30 days of consent
  11. Ventricular tachycardia ≥ 20 consecutive beats without an ICD within 3 months of consent, or symptomatic Mobitz II or higher degree atrioventricular block without a functioning pacemaker within 3 months of consent
  12. Presence of LV thrombus
  13. Evidence of active myocarditis
  14. Baseline maximal oxygen consumption (VO2 max) greater than 75% of age and gender based predictive values
  15. Baseline eGFR <35 ml/min/1.73m2
  16. Blood glucose levels (HbA1c) >10%
  17. Hematologic abnormality evidenced by hematocrit < 25%, white blood cell < 2,500/ul or platelet count < 100,000/ul
  18. Liver dysfunction evidenced by enzymes (AST and ALT) ˃ 3 times the upper limit of normal (ULN)
  19. Coagulopathy (INR ≥ 1.3) not due to a reversible cause (e.g., warfarin and/or Factor Xa inhibitors). Subjects who cannot be withdrawn from anticoagulation will be excluded.
  20. HIV and/or active hepatitis B virus (HBV) or hepatitis C virus (HCV)
  21. Allergy to radiographic contrast material that cannot adequately be managed by premedication
  22. Known history of anaphylactic reaction to penicillin or streptomycin
  23. Received gene or cell-based therapy from any source within the previous 12 months
  24. History of malignancy within 5 years (i.e., subjects with prior malignancy must be disease free for 5 years), excluding basal cell carcinoma and cervical carcinoma in situ which have been definitively treated
  25. Condition that limits lifespan to < 1 year
  26. History of drug abuse (illegal "street" drugs except marijuana, or prescription medications not being used appropriately for a pre-existing medical condition) or alcohol abuse (≥ 5 drinks/day for ˃ 3 months), or documented medical, occupational, or legal problems arising from the use of alcohol or drugs within the past 24 months
  27. Participation in an investigational therapeutic or device trial within 30 days of consent
  28. Cognitive or language barriers that prohibit obtaining informed consent or any study elements
  29. Pregnancy or lactation or plans to become pregnant in the next 12 months
  30. Any other condition that, in the judgment of the Investigator or Sponsor, would impair enrollment, study product administration, or follow-up

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02501811


Contacts
Contact: Rachel Vojvodic, MPH 713-500-9528 Rachel.W.Vojvodic@uth.tmc.edu
Contact: Lemuel Moye, MD, PhD 713-500-9518 Lemmoye@msn.com

Locations
United States, California
Stanford University School of Medicine (Falk Cardiovascular Research Center) Recruiting
Stanford, California, United States, 94305
Contact: Fouzia Khan    650-736-1410    fouziak@stanford.edu   
Contact: Divya Rajmohan    650-721-6092    rajmohan@stanford.edu   
Principal Investigator: Phil Yang, MD         
United States, Florida
University of Florida-Department of Medicine Recruiting
Gainesville, Florida, United States, 32610
Contact: Sarah Long    352-273-8932    Sarah.Long@medicine.ufl.edu   
Contact: Nicole Bostick    352-273-8938    Janette.Bostick@medicine.ufl.edu   
Principal Investigator: Carl J Pepine, MD         
University of Miami-Interdisciplinary Stem Cell Institute Recruiting
Miami, Florida, United States, 33101
Contact: Lina Caceres    305-243-5399    lvc25@med.miami.edu   
Contact: Jairo Tovar    305-243-5399    JAT243@med.miami.edu   
Principal Investigator: Raul Mitrani, MD         
United States, Indiana
Indiana Center for Vascular Biology and Medicine Active, not recruiting
Indianapolis, Indiana, United States, 46202
United States, Kentucky
University of Louisville Recruiting
Louisville, Kentucky, United States, 40202
Contact: Shari Williams    502-407-3259    shari.williams@louisville.edu   
Contact: Heidi Wilson    502-852-5547    heidi.wilson@louisville.edu   
Principal Investigator: Roberto Bolli, MD         
United States, Minnesota
Minneapolis Heart Institute Foundation Recruiting
Minneapolis, Minnesota, United States, 55407
Contact: Jane Fox    612-863-6289    Jane.fox@allina.com   
Principal Investigator: Jay Traverse, MD         
United States, Texas
Texas Heart Institute Recruiting
Houston, Texas, United States, 77030
Contact: James Chen    832-355-9405    jchen@texasheart.org   
Contact: Nichole Piece    832-355-9173    npiece@texasheart.org   
Principal Investigator: James T Willerson, MD         
Sponsors and Collaborators
The University of Texas Health Science Center, Houston
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Study Chair: Robert Simari, MD CCTRN Steering Committee Chair

Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dr Lemuel A Moye III, Professor of Biostatistics, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier: NCT02501811     History of Changes
Other Study ID Numbers: HSC-SPH-15-0413
5UM1HL087318 ( U.S. NIH Grant/Contract )
First Posted: July 17, 2015    Key Record Dates
Last Update Posted: May 17, 2018
Last Verified: May 2018

Keywords provided by Dr Lemuel A Moye III, The University of Texas Health Science Center, Houston:
Heart Failure
Ischemia
Autologous Stem Cells
LV dysfunction
Mesenchymal Stem Cells
ckit Cardiac Stem Cells
Combination Cell Therapy
LV function
Functional status

Additional relevant MeSH terms:
Heart Failure
Ischemia
Cardiomyopathies
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Plasma-lyte 148
Ophthalmic Solutions
Pharmaceutical Solutions