The TRansendocardial Stem Cell Injection Delivery Effects on Neomyogenesis STudy (The TRIDENT Study)
Condition: Chronic Ischemic Left Ventricular Dysfunction; Myocardial Infarction
MeSH terms: Myocardial Infarction; Ventricular Dysfunction; Ventricular Dysfunction, Left; Ischemia; Infarction
Intervention: Allogeneic hMSCs
Intervention description: Allogeneic Adult Human Mesenchymal Stem Cells (MSCs) delivered via injection
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 30.0
Sex: All
Minimum age: 21 Years
Maximum age: 90 Years
Healthy volunteers: No
Keywords: Cardiovascular; Chronic Ischemic Left Ventricular Dysfunction

Summary:

      Thirty (30) patients with chronic ischemic left ventricular dysfunction secondary to MI
      scheduled to undergo cardiac catheterization will be enrolled in the study. This is a phase
      II study intended to gain additional safety and efficacy assessments among two dose levels
      previously studied in a phase I setting.
    

Eligibility criteria:

        Inclusion Criteria:

          -  In order to participate in this study, a patient MUST:

               1. Be ≥ 21 and < 90 years of age.

               2. Provide written informed consent.

               3. Have a diagnosis of chronic ischemic left ventricular dysfunction secondary to
                  myocardial infarction (MI) as defined by previous myocardial infarction
                  documented by an imaging study demonstrating coronary artery disease with
                  corresponding areas of akinesis, dyskinesis, or severe hypokinesis.

               4. Been treated with appropriate maximal medical therapy for heart failure or
                  post-infarction left ventricular dysfunction. For beta-blockade, the patient must
                  have been on a stable dose of a clinically appropriate beta-blocker for 3 months.
                  For angiotensin-converting enzyme inhibition, the patient must have been on a
                  stable dose of a clinically appropriate agent for 1 month.

               5. Be a candidate for cardiac catheterization within 5 to 10 weeks of screening as
                  determined by doctors.

               6. Have an ejection fraction of less than or equal to 50% by gated blood pool scan,
                  two-dimensional echocardiogram, CT, or left ventriculogram within the prior six
                  months and not in the setting of a recent ischemic event.

        Exclusion Criteria:

          -  In order to participate in this study, a patient MUST NOT:

               1. Have a baseline glomerular filtration rate ≤ 35 ml/min/1.73m2.

               2. Have a known, serious radiographic contrast allergy.

               3. Have a Mechanical aortic valve or heart constrictive device.

               4. Have a documented presence of aortic stenosis (aortic stenosis graded as 1.5cm2
                  or less).

               5. Have a documented presence of moderate to severe aortic insufficiency
                  (echocardiographic assessment of aortic insufficiency graded as ≥+2).

               6. Require coronary artery revascularization. Patients who require or undergo
                  revascularization procedures should undergo these procedures a minimum of 3
                  months in advance of treatment in this study. In addition, patients who develop a
                  need for revascularization following enrollment will be submitted for this
                  therapy without delay.

               7. Have evidence of a life-threatening arrhythmia in the absence of a defibrillator
                  (non-sustained ventricular tachycardia ≥ 20 consecutive beats or complete second
                  or third degree heart block in the absence of a functioning pacemaker) or
                  Corrected for heart rate (QTc) interval > 550 ms on screening ECG

               8. Automatic Implantable Cardioverter Defibrillator (AICD) firing in the past 60
                  days prior to enrollment.

               9. Have a hematologic abnormality as evidenced by hematocrit < 25%, white blood cell
                  < 2,500/µl or platelet values < 100,000/µl without another explanation.

              10. Have liver dysfunction, as evidenced by enzymes (AST and ALT) greater than three
                  times the upper limit of normal (ULN).

              11. Have a coagulopathy = (INR > 1.3) not due to a reversible cause (i.e., Coumadin).
                  Patients on Coumadin will be withdrawn 5 days before the procedure and confirmed
                  to have an INR < 1.3. Patients who cannot be withdrawn from Coumadin will be
                  excluded from enrollment

              12. Have known allergies to penicillin or streptomycin.

              13. Hypersensitivity to Dimethyl Sulfoxide (DMSO).

              14. Be an organ transplant recipient.

              15. Have a history of organ or cell transplant rejection

              16. Have a clinical history of malignancy within 5 years (i.e., patients with prior
                  malignancy must be disease free for 5 years), except curatively-treated basal
                  cell carcinoma, squamous cell carcinoma, melanoma in situ or cervical carcinoma.

              17. Have a non-cardiac condition that limits lifespan to < 1 year.

              18. Have a history of drug or alcohol abuse within the past 24 months.

              19. Be on chronic therapy with immunosuppressant medication, such as corticosteroids
                  or TNFα antagonists.

              20. Be serum positive for HIV, hepatitis BsAg or viremic hepatitis C.

              21. Be currently participating (or participated within the previous 30 days) in an
                  investigational therapeutic or device trial.

              22. Be a female who is pregnant, nursing, or of childbearing potential while not
                  practicing effective contraceptive methods. Female patients must undergo a blood
                  or urine pregnancy test at screening and within 36 hours prior to injection.