Intra-coronary Infusion of Bone Marrow Derived Autologous CD34+ Selected Cells in Patients With Acute Myocardial Infarction

Study Overview
=================
Brief Summary
-----------------
Following a Heart attack the acute loss of heart muscle cells results in a cascade of events causing an immediate decrease in cardiac function that has the potential to persist long term. Despite revascularization of the infarct related artery circulation and appropriate medical management to minimize the stresses on the heart walls, a significant percentage of patients experience permanent cardiac dysfunction and consequently remain at an increased life-time risk of experiencing adverse cardiac events, including death. There is a great potential for stem cell therapy, using a variety of cell precursors (particularly hematopoietic,)to contribute to new blood vessel formation (and possibly limited heart muscle formation) and muscle preservation in the myocardial infarct zone. The administration of cells via an infusion through the infarct related artery appears to be feasible and result in a clinical effect in some studies. Therefore, we propose to evaluate the safety and efficacy of a CD34+ selected stem cell product (AMR-001), administered through the infarct related coronary artery 6 to 9 days after successful infarct related artery stent placement. The primary objective of the study is to determine the feasibility and safety of prospectively identifying patients at risk for clinically significant cardiac dysfunction following a myocardial infarction and the ability to isolate and infuse via the affected coronary circulation an autologous bone marrow derived CD34+ cell product at four dose levels. The secondary objective of the study is to assess the effect on cardiac function and infarct region perfusion. A concurrent patient group meeting eligibility but not receiving CD34+ cells will be evaluated similar to the treated group to assess the rate of significant spontaneous improvement in cardiac function without CD34+cell infusion.

Official Title
-----------------
AMORCYTE MYOCARDIAL REPAIR STUDY- A Phase I Trial of Intra-coronary Infusion of Bone Marrow Derived Autologous CD34+ Selected Cells in Patients With Acute Myocardial Infarction. (AMRS)

Conditions
-----------------
Myocardial Infarction, Coronary Artery Disease

Intervention / Treatment
-----------------
* Drug: Intra-coronary infusion


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18 - 75 years. Acute ST elevation myocardial infarction meeting ACC/AHA criteria, with symptoms of chest pain within 3 days of admission. Criteria include (ST elevation > 1mm in limb leads or 2 mm in two or more precordial leads and increased levels of troponin, CPK MB or both) NYHA heart failure class of I, II or III Exclusion Criteria: Patients who are not candidates for percutaneous intervention, conscious sedation, MRI, SPECT imaging or mini-bone marrow harvest History of sustained chest pain unrelieved by nitrates, occurring 4 or more days before revascularization. Patients who fail to re-perfuse the infarct related coronary artery or have successful stent placement

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 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: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control Group<br>A concurrent group meeting eligibility criteria but not receiving CD34+cells will be evaluated similar to the study group to assess the extent, if any, of significant improvement in cardiac perfusion/function without the CD34+cell product infusion. | |
| Experimental: Treatment Group<br>Intra-coronary infusion of an autologous bone marrow derived CD34+ stem cell product. | Drug: Intra-coronary infusion<br>* In our study there will be four dosing cohorts (5, 10, 20 and 30 x 106) of CD34+ cells.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiac function at 3 and 6 months follow-up will be compared to baseline measures obtained the day(s) before CD34+ cell product infusion. |  | 3 & 6 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Perfusion of the infarct region at 6 months follow-up will be compared to baseline measures obtained the day(s) before CD34+ cell product infusion |  | 6 Months | 
| An assessment will be performed to determine if a correlation exist between clinical outcome and cell content (CD34+) and/or in vitro colony growth (CFU-GM, CFU-GEMM, BFU-E) CXCR-4 mobility and CXCR-4 and/or VEGF surface antigen expression. |  | Baseline | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
myocardial infarction, bone marrow, cd34+, stem cells