Safety & Efficacy of Adipose-Derived Regenerative Cells in the Treatment of Chronic Myocardial Ischemia (ATHENA II)

Study Overview
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Brief Summary
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This is a prospective, randomized, placebo-controlled, double blind safety and efficacy clinical trial.

Detailed Description
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To assess the safety and efficacy of Adipose-Derived Regenerative Cells (ADRCs) delivered via an intramyocardial route in the treatment of chronic ischemic heart disease in patients who are not eligible for percutaneous or surgical revascularization.

Official Title
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Adipose-derived Regenerative Cells in the Treatment of Patients With Chronic Ischemic Heart Disease Not Amenable to Surgical or Interventional Revascularization II

Conditions
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Myocardial Ischemia

Intervention / Treatment
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* Device: Celution System
* Device: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females > 20 and < 80 years of age Significant multi-vessel coronary artery disease not amenable to percutaneous or surgical revascularization CCS Angina Functional Class II-IV and/or NYHA Stages of Heart Failure Class II or III On maximal medical therapy for anginal symptoms and/or heart failure symptoms Hemodynamic stability (SBP ≥ 90 mm/Hg, HR <110) Ejection fraction ≥ 20% and ≤ 45% Inducible ischemia using an objective assessment of ischemia within 1 year of screening (i.e. exercise ECG changes, SPECT) Left ventricular wall thickness ≥ 8 mm at the target site for cell injection Exclusion Criteria: Atrial fibrillation or flutter without a pace maker that guarantees a stable heart rate Unstable angina LV thrombus, as documented by echocardiography Planned staged treatment of CAD or other intervention on the heart Platelet count < 100,000/mm3 WBC < 2,000/mm3 TIA or stroke within 90 days prior to randomization ICD shock within 30 days prior to randomization Any condition requiring immunosuppressive medication A high-risk acute coronary syndrome (ACS) or a myocardial infarction in the 60 days prior to randomization Revascularization within 60 days prior to randomization Inability to walk on a treadmill except for class IV angina patients who will be evaluated separately Hepatic dysfunction, as defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 1.5 times the upper limit of normal range (x ULN) Hemoglobin ≤ 10.0 g/dL

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ADRCs<br>Adipose-Derived Regenerative Cells (ADRCs) processed by the Celution System: 0.8 x 10^6 cells/kg body weight (not to exceed 80.0 x 10^6 cells) Delivered via the MYOSTAR™ Injection Catheter in 15 intramyocardial injections | Device: Celution System<br>* ADRCs processed by the Celution System for reintroduction into the myocardium<br>|
| Placebo Comparator: Placebo<br>Placebo - Physiological Solution Inactive substance (Lactated Ringers + autologous blood) Delivered via the MYOSTAR™ Injection Catheter in 15 intramyocardial injections | Device: Placebo<br>* Physiological solution made of Lactated Ringers solution and a small amount (<1mL) of autologous blood<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Efficacy - Change in Minnesota Living with Heart Failure Questionnaire | Change in Minnesota Living with Heart Failure Questionnaire prior to treatment and at 6 months post treatment. | 6 months post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Efficacy - Change in mVO2 | Change in mVO2 at 6 months as assessed by Exercise Tolerance Test | 6 months post treatment | 
| Secondary Efficacy - Change in LVESV/LVEDV | Change in LVESV/LVEDV at 6 months as assessed by Echocardiography | 6 months post treatment | 
| Secondary Efficacy - Change in Ejection Fraction | Change in Ejection Fraction (%) at 6 months assessed by 2D Contrast Echocardiography | 6 months post treatment | 
| Secondary Efficacy - Change in perfusion defect | Change in perfusion defect at 6 months assessed by Rest/Pharmacologic Stress SPECT | 6 months post treatment | 
| Secondary Efficacy - Resource Utilization | Resource utilization - hospital length of stay, re-hospitalization for cardiac related events | through 12 months post treatment | 
| Secondary Efficacy - Change in heart failure symptoms, angina, and quality of life | Change in heart failure symptoms, angina, and quality of life assessed by - NYHA classification, CCS classification, MLHFQ (other than 6 months) | through 12 months post treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ischemic heart disease, Coronary artery disease, Chronic Heart Failure, Cardiovascular disease, adult stem cells, adipose derived regenerative cells