Intracardiac CD133+ Cells in Patients With No-option Resistant Angina

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to evaluate the efficacy of therapy with autological CD133+ cells in patients with angina resistant to pharmacological treatment and without the possibility of effective revascularization. Cells will be isolated from patients bone marrow and administered directly into the muscle of left ventricle. The main objective is to assess the treatments' influence on improvement of myocardial perfusion and function, and on decrease of occurrence of symptomatic angina.

Detailed Description
-----------------
Patients with a Stable angina pectoris (CCS II-IV) can potentially benefit from treatment with autological CD133+ cell populations, which include cells with a higher expression of cardiac and endothelial differentiation markers. REGENT VSEL Trial will include Patients with Angina resistant to pharmacological treatment and without the possibility of effective revascularization. The main objective of the study is to assess the treatments influence on: improvement of myocardial perfusion global and segmental contractility (LVEF) occurrence of symptomatic angina quality of life Regent Vsel is a prospective, randomized, double blind, placebo-controlled study with a planned number of 60 Patients. Randomization will be carried out according to a 1:1 mode. Every Patient will undergo a bone marrow aspiration. CD133+ cells will be isolated from bone marrow aspirates. Patients randomized to experimental group will receive isolated cells (direct left ventricular muscle administration). Patients enrolled to control group will get only a placebo solution injected into the muscle.

Official Title
-----------------
A Randomized,Prospective,Double-blind Study to Evaluate Intracardiac Injections of Bone Marrow,Autologous CD133+Cells(Electromechanical Mapping Based)in Patients With Resistant Angina and no Effective Revascularization Option. RegentVsel

Conditions
-----------------
Stable Angina

Intervention / Treatment
-----------------
* Biological: intramyocardial injection (electromechanical mapping based)
* Biological: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Stable angina CCS II-IV despite maximum pharmacotherapy for at least 2 weeks since last medications change Presence of ≥ 1 myocardial segment with ischemia features in Tc-99m SPECT Patients disqualified from revascularization procedures by Heart Team Patient age > 18 and < 75 year old Patient must provide written informed consent for participation in study Exclusion Criteria: Acute coronary syndrome in less than 6 months prior to enrollment Heart failure NYHA III-IV LVEF <35% Presence of intracardiac thrombus (echocardiography confirmed), massive calcification of the aortic valve and left ventricular aneurysm Previous cardioverter-defibrillator or cardiac stimulator implantation Allergy to contrast agents History of malignancy HIV, HBV, HCV infection Life expectancy less than 6 months Bleeding diathesis Renal insufficiency (GFR < 30 mL/min/1.73m2) Pregnancy, lactation, or ineffective contraception in women of childbearing potential

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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CD133+<br>intramyocardial injection (electromechanical mapping based) of autological CD133+ cells, isolated from bone marrow | Biological: intramyocardial injection (electromechanical mapping based)<br>* Patient will undergo 3D electric and mechanical intracardiac mapping; based on maps generated intramyocardial administration of autologous CD133+ cells or placebo will be performed.<br>|
| Placebo Comparator: Placebo<br>intramyocardial injection (electromechanical mapping based) of placebo - 0,9% NaCl plus 0,5% solution of patients' serum | Biological: Placebo<br>* Patients in the placebo group receive 0.9% NaCl solution with 0.5% solution of the patient's own serum.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myocardial perfusion change | Myocardial perfusion change assessed by perfusion scintigraphy (99mTc SPECT) | 4 months after application of cell therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global and segmental contractility change and myocardial perfusion change | Global and segmental contractility change and myocardial perfusion change assessed by magnetic resonance imaging with adenosine administration, and echocardiography with contrast | MRI 4 months and echocardiography 4 and 12 months after application of cell therapy | 
| Exercise tolerance | Exercise tolerance assessed in a treadmill test (TET, ESTD, TTLA) | 4 and 12 months after application of cell therapy | 
| Occurrence of symptomatic angina | CCS, nitrates usage | 1, 4, 6 and 12 months after application of cell therapy | 
| Quality of life | Quality of life assessed by standard questionnaires: SF37, Seattle Angina | 1, 4, 6 and 12 months after application of cell therapy | 
| Occurrence of ventricular arrhythmia | 24 hrs ECG monitoring | 1, 4, 6 and 12 months after application of cell therapy | 
| Occurrence of in-stent restenosis and progression of artherosclerotic lesions in remained coronary artery segments | Assessed by Intravascular Ultrasound (IVUS) and Optical coherence tomography (OCT) examination | 4 months after application of cell therapy | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
CD133+, stem cells, Coronary Artery Disease, Stable Angina Pectoris