Combination of Mesenchymal and C-kit+ Cardiac Stem Cells as Regenerative Therapy for Heart Failure
Condition: Ischemic Cardiomyopathy
MeSH terms: Cardiomyopathies
Intervention: Mesenchymal Stem Cells (MSC); c-kit+ cells; Placebo (Plasmalyte A)
Intervention description: 15 transendocardial injections of 0.4ml MSCs administered to the left ventricle via NOGA Myostar injection catheter (single procedure); 15 transendocardial injections of 0.4ml c-kit+ cells administered to the left ventricle via NOGA Myostar injection catheter (single procedure); 15 transendocardial injections of 0.4ml placebo administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
Intervention MeSH terms: Plasma-lyte 148
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 125.0
Sex: All
Minimum age: 21 Years
Maximum age: 79 Years
Healthy volunteers: No
Keywords: Heart Failure; Ischemia; Autologous Stem Cells; LV dysfunction; Mesenchymal Stem Cells; c-kit+ Cells; Combination Cell Therapy; LV function; Functional status

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+ cells 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.
    

Eligibility 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