Safety and Feasibility Trial of Adipose-Derived Regenerative Cells in the Treatment of Chronic Myocardial Ischemia

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

Detailed Description
-----------------
To assess the safety and feasibility 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
-----------------
Adipose-derived Regenerative Cells in the Treatment of Patients With Chronic Ischemic Heart Disease Not Amenable to Surgical or Interventional Revascularization.

Conditions
-----------------
Myocardial Ischemia

Intervention / Treatment
-----------------
* Device: ADRCs processed by the Celution System
* Device: Placebo Comparator: Lactated Ringer's and Subject's Blood


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Males or females 20-80 years of age Significant multi-vessel coronary artery disease not amenable to percutaneous or surgical revascularization in the target area 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 (Systolic Blood Pressure ≥ 90 mm/Hg, Heart Rate < 110; Pulse-Oxygen > 95) Ejection fraction ≤ 45 Left ventricular wall thickness ≥ 8 mm at the target site for cell injection, confirmed by 2D contrast echo within 4 weeks prior to enrollment, free of thrombus Key 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 of randomization Any condition requiring immunosuppressive medication A high-risk acute coronary syndrome (ACS) or a myocardial infarction within 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) prior to randomization

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ADRCs processed by the Celution System<br>400,000 adipose-derived regenerative cells (ADRCs) per kilogram (kg) of body weight not to exceed 40,000,000 cells. | Device: ADRCs processed by the Celution System<br>* Subjects will undergo liposuction under anesthesia. Lipoaspirate will be processed in the Celution System to isolate and concentrate ADRCs. When randomized to ADRCs, intramyocardial injections of ADRCs will be administered via the MYOSTAR injection catheter.<br>* Other names: Intramyocardial injections;|
| Placebo Comparator: Lactated Ringers and Subject's blood<br>Sterile Lactated Ringers Solution (3mL) mixed with ≤ 0.10 ml of the study Subject's own freshly drawn blood. | Device: Placebo Comparator: Lactated Ringer's and Subject's Blood<br>* Subjects will undergo liposuction under anesthesia. Lipoaspirate will be processed in the Celution System to isolate and concentrate ADRCs. When randomized to Placebo, intramyocardial injections of Placebo will be administered via the MYOSTAR injection catheter.<br>* Other names: Placebo;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment emergent serious adverse events (SAEs), major adverse cardiac events (MACE), arrhythmia assessment, change in cardiac function and symptoms, and resource utilization | Safety endpoints include: Treatment emergent SAEs Arrhythmia assessment via Holter monitoring MACE defined as cardiac death and hospitalization for heart failure Feasibility endpoints include: Change in mVO2 at 6 months Change in LVESV/LVEDV at 6 months Change in ejection fraction at 6 months Change in perfusion defect at 6 months Resource utilization Change in heart failure symptoms, angina, and quality of life through 12 months | 6 and 12 Months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Ischemic heart disease, Coronary artery disease, Chronic heart failure, Cardiovascular disease, Adult stem cells, Adipose derived regenerative cells