Adipose Stromal Cells Injection in the Myocardium for Induction of Revascularization

Study Overview
=================
Brief Summary
-----------------
Treatment of ischemic myocardium has been the subject of intense research in recent years and stem cell therapy is one of the great promises. The InCor laboratory has studied cells from different backgrounds as candidates for cell therapy in the context of myocardial infarction. Evidence in preclinical studies of the application of stromal (mesenchymal) adipose tissue (hASC) in the ischemic heart by both the InCor group (in the animal model in rodents and pigs) and others in the literature suggest relevant benefits on the decrease of deterioration post-infarction. More recently it has been demonstrated that it arises mainly from the formation of new vessels due to paracrine factors, which are secreted by the injected cells. There are currently no studies in Brazil in which the safety of injecting different doses of hASC cells into the heart has been particularly evaluated. Recently, two studies have demonstrated the clinical applicability of hASC in patients with peripheral ischemic disease and stroke. Thus, the objective of this work will be to test the hypothesis that the implantation of autologous stromal cells derived from adipose tissue combined with myocardial revascularization surgery in patients with coronary artery disease

Detailed Description
-----------------
To test the hypothesis that the implantation of adipose-derived autologous cells derived from adipose tissue (hASCs) combined with coronary artery bypass grafting in patients with coronary artery disease is safe and well tolerated, besides being able to promote regional perfusion increase in the injected segments.

Official Title
-----------------
Adipose Stromal Cells Injection in the Myocardium for Induction of Revascularization

Conditions
-----------------
Ischemic Heart Disease, Myocardial Ischemia, Coronary Artery Disease

Intervention / Treatment
-----------------
* Biological: Stromal Cells Injection


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: signing the Informed Consent Form (TCLE) the patient must be a patient with obstructive atherosclerotic coronary artery disease sex: both men and women are eligible- Age: between 18 and 80 years of age the patient should present clinical evidence (angina pectoris or angina equivalent) OR imaging (stress echocardiography, myocardial perfusion scintigraphy, cardiac magnetic resonance imaging) of myocardial ischemia, invasively stratified with coronary angiography the presence of myocardial ischemia should be confirmed by at least 2 (two) distinct diagnostic methods performed within one year of the patient's inclusion in the study the patient is a candidate for myocardial revascularization surgery but coronary obstructive lesions, in their entirety, are NOT amenable for surgical treatment in the opinion of the surgeon (main surgeon), depending on the anatomical type, extent or distal involvement of the lesions OR, even if they can be treated surgically as a whole, an unsatisfactory surgical outcome is anticipated in terms of functional gain (restoration of myocardial perfusion) Exclusion Criteria: do not meet ALL criteria for inclusion have a concomitant severe disease, at an advanced stage, or with an unquestionable shortening of life expectancy (<1 year), or that prevents complementary examinations and / or attendance at follow-up visits have a confirmed diagnosis, previous history and / or past treatment of neoplasia, of any location and staging, in the last 5 years being in clinical treatment or awaiting surgical treatment of neoplasia, any location and staging present, during the outpatient investigation, unequivocal findings of neoplasia have symptoms attributable exclusively to left ventricular dysfunction, although of ischemic etiology, without the evidence of current myocardial ischemia, by at least two (2) methods of evaluation presented severe left ventricular dysfunction as defined by transthoracic echocardiography due to the finding of a left ventricular ejection fraction <0.25 (Simpson's method) have a history or current diagnosis of severe ventricular arrhythmias such as sustained ventricular tachycardia unless an automatic cardioverter-defibrillator has been implanted previously Concurrent heart diseases of other etiologies (valvular, idiopathic, hypertensive, Chagasic, etc.). have a history of acute coronary syndrome (unstable angina or acute myocardial infarction) in the last 3 months present chronic renal failure in dialysis treatment have participated in other cell therapy studies in the past 2 years Pregnant women patients diagnosed with acquired immunodeficiency syndrome (AIDS)

Ages Eligible for Study
-----------------
Minimum Age: 18 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
Interventional Model Description: It is a randomized, prospective, double-blind, placebo-controlled clinical study. Eligible patients will be randomly divided into 4 groups (one control group and 3 active treatment groups): 10 PATIENTS EACH ARM Control Group - saline injection Low dose group (BD) - hASC injection (1x106 / kg body weight) Intermediate dose group (DI) - injection of hASC (2x106 / kg body weight) High dose group (AD) - hASC injection (4x106 / kg body weight)
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: PLACEBO GROUP<br>injection of saline solution | Biological: Stromal Cells Injection<br>* Adipose stromal cell<br>|
| Active Comparator: Low dose group<br>hASC injection (1x10e6 / kg body weight) | Biological: Stromal Cells Injection<br>* Adipose stromal cell<br>|
| Active Comparator: Intermediate Dose<br>injection of hASC (2x10e6 / kg of body weight) | Biological: Stromal Cells Injection<br>* Adipose stromal cell<br>|
| Active Comparator: High dose group<br>injection of hASC (4x10e6 / kg body weight) | Biological: Stromal Cells Injection<br>* Adipose stromal cell<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiovascular Death | Death due to stroke, myocardial infarction or other cardiovascular causes | 12 months | 
| Unstable angina | Occurence of angina requiring hospitalization | 12 months | 
| Acute myocardial infarction | Occurence of acute myocardial infarction (with or without ST segment elevation) | 12 months after procedure | 
| Unplanned myocardial revascularization surgery | Need for urgent surgical myocardial revascularization | 12 months | 
| Unplanned myocardial revascularization through angioplasty | Need for urgent non-surgical myocardial revascularization | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All cause mortality |  | 12 months | 
| Stroke |  | 12 months | 
| Cardiogenic shock |  | 12 months | 
| Occurence of complex ventricular arrhythmia |  | 12 months | 
| New onset atrial fibrilation |  | 12 months | 
| Occurence of acute pulmonary edema |  | 12 months | 
| Pulmonary embolism |  | 12 months | 
| Acute respiratory failure of any cause |  | 12 months | 
| Septic shock | Disseminated infection requiring vasopressors | 12 months | 
| New onset cancer | Diagnosis of any cancer at any stage during study period | 12 month | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
STROMAL CELLS, ADIPOSE STROMAL CELLS, REVASCULARIZATION, MYOCARDIUM REVASCULARIZATION, CARDIAC SURGERY, CORONARY ARTERY DISEASE