Serial Infusions of Allogeneic Mesenchymal Stem Cells in Cardiomyopathy Patients With Left Ventricular Assist Device
Condition: Ischemic Heart Disease; Non-ischemic Cardiomyopathy
MeSH terms: Heart Diseases; Cardiomyopathies; Myocardial Ischemia; Coronary Artery Disease
Intervention: Human Allogeneic Mesenchymal Bone Marrow Cells (aMBMC); Placebo
Intervention description: Allogeneic Mesenchymal Bone Marrow Cells (aMBMC) 1.5 million cells/kg; 1.5 mL/kg Lactated Ringer's Solution
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 4.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      A study to assess the safety and preliminary efficacy of serial intravenous dose of
      Allogeneic Mesenchymal Bone Marrow Cells in subjects with heart failure and implanted left
      ventricular assist devices.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age ≥18 years.

          2. Advanced Heart Failure

          3. Advanced HF defined as HF requiring LVAD implantation and deemed stable on his/her
             LVAD.

          4. On stable medical therapy (per the discretion of the treating physician) including
             beta-blockers, ACE-inhibitors, angiotensin receptors blockers, angiotensin receptor
             neprilysin inhibitor, mineralocorticoid receptor antagonists, isosorbide, hydralazine,
             and mineralocorticoid receptor antagonists) and optimized pump speed for at least a
             month prior to randomization.

          5. HS-CRP level≥2 mg/l.

          6. NYHA class II-III symptoms.

          7. Ability to understand and provide signed informed consent.

          8. Reasonable expectation that patient will receive standard post-treatment care and
             attend all scheduled safety follow-up visits

        Exclusion Criteria:

          1. Women of childbearing potential. Postmenopausal women or women with permanent
             contraception method (defined as total hysterectomy) will not be excluded.

          2. History of debilitating stroke (modified Rankin Score > 3) within 3 months.

          3. The likelihood of requirement of cardiac surgery during the study period.

          4. Presence of clinically significant, uncorrected left sided valvular heart disease,
             active acute myocarditis, or uncontrolled hypertension defined as Persistently
             elevated mean arterial blood pressure (>100 mmHg). Echocardiography within 12 months
             of screening. Patients can be re-evaluated, at the discretion of the investigator.

          5. QTc >550 ms (in the absence of bundle branch block, interventricular conduction delay
             or ventricular pacing). Electrocardiogram (ECG) within 60 days.

          6. History of cardiac arrest within 3 months.

          7. Hypertrophic or infiltrative cardiomyopathy.

          8. Considered or listed for organ transplantation or history of organ transplantation

          9. Illness other than HF with life expectancy less than 12 months.

         10. Enrolled in an interventional trial or received an experimental drug or device within
             30 days of randomization.

         11. Left ventricular assist device implantation >2 years prior to enrollment.

         12. Biventricular assist device (Bi-VAD) support.

         13. Severe COPD defined by FEV1<1L, FEV1/FVC<70% within 12 months if known history of
             COPD, otherwise FEV1<1L, FEV1/FVC<70% within 24 months

         14. Uncontrolled seizure disorder.

         15. Clinically significant hematologic, hepatic, or renal impairment as determined by
             screening clinical laboratory tests within the last 30 days:

             Liver disease = ALT or AST > 3x normal, alkaline phosphatase or bilirubin >2x normal
             Renal disease = on long term dialysis Hematologic = Unexplained persistent
             leukocytosis (WBC >11 K/UL) or hemoglobin < 8.5 gm/dl

         16. Presence of any other clinically-significant medical condition, psychiatric condition,
             or laboratory abnormality, that in the judgment of the investigator or sponsor may
             affect compliance with the study protocol or pose a safety risk to the subject.

         17. Inability to comply with the conditions of the protocol.

         18. Acute coronary syndrome within 4 weeks (clinical diagnosis, confirmed by
             electrocardiographic abnormalities and elevation of troponin-I).

         19. Malignancy within the previous five years, except adequately treated basal cell
             carcinoma, provided that it is neither infiltrating nor sclerosing, and carcinoma in
             situ of the cervix.

         20. Active uncontrolled systemic infection. Positive blood or deep tissue cultures or
             clinical or imaging evidence of systemic infection despite complete course of
             effective antimicrobial therapy as determined by infectious diseases. Localized
             (non-systemic) infection is not an exclusion criterion. Patients can be re-evaluated,
             at the discretion of the investigator.

         21. Early postpartum cardiomyopathy (within six months of diagnosis).

         22. Presence of inherited or acquired immune deficiency or human immunodeficiency virus
             infection (HIV). Negative HIV test within the preceding 12 months is required.

         23. Systemic corticosteroids, immunosuppressive drug therapy (cyclophosphamide,
             methotrexate, cyclosporine, tacrolimus, azathioprine, mycophenolate, sirolimus, etc.),
             and DNA depleting or cytotoxic drugs taken within four weeks prior to study treatment.

         24. Known Porphyria.

         25. Allergy to sodium citrate or any caine type of local anesthetic.

         26. Patient enrolled in hospice care.