The Application of the Umbilical Cord Mesenchymal Stem Cells in the Complex Treatment of Non-ischemic Heart Failure

Study Overview
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Brief Summary
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The purpose of this study is to optimize the complex treatment of chronic heart failure of non-ischemic etiology by supplementing umbilical cord mesenchymal stem cells to the standard drug therapy.

Detailed Description
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The purpose of this study is to optimize the complex treatment of non-ischemic dilated cardiomyopathy by supplementing the standard drug therapy with intracoronary administration of umbilical cord-derived mesenchymal stromal cells. Sixty patients will be selected and randomly divided into the main and control groups in a 1: 1 ratio. Patients of the main group will receive complex treatment based on the addition to the standard drug therapy of intracoronary administration of 10 million mesenchymal stromal cells of the umbilical cord, and patients of the control group will receive only standard drug therapy. Every patient will maintain their standard treatment of chronic heart failure, with maximum tolerated dosage without side effects. The day of infusion will be considered day zero. From that moment, followup will be divided into 0-1,1-3 and 3-6 months. Clinical results will be analyzed after completion of 6 months of followup.

Official Title
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Optimization of the Complex Treatment of Nonischemic Dilated Cardiomyopathy Due to the Addition to the Standard Drug Therapy of Intracoronary Administration of Umbilical Cord-derived Mesenchymal Stromal Cells

Conditions
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Chronic Heart Failure, Non-ischemic Cardiomyopathy, Non-ischemic Dilated Cardiomyopathy

Intervention / Treatment
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* Procedure: Cardiac catheterization
* Biological: Intracoronary administration of the umbilical cord-derived mesenchymal stromal cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women over 18 years of age, who are registered in the dispensary at the The Research-Clinical Center for Cardiac Surgery and Transplantology; The previously established clinical diagnosis of Dilated cardiomyopathy in the stage III-IV of New York Heart Association classification; Non-ischemic etiology of Dilated cardiomyopathy according to coronary angiography or computed tomography of the heart with contrast; Decreased contractile function of the heart the left ventricular ejection fraction ≤35% according to transthoracic echocardiography and computed tomography of the heart with contrast; Presence of automatic (implantable) cardiac defibrillator; Lack of laboratory and clinical data on dysfunctions or insufficiency of other internal organs; The absence of a history of cancer over the past 5 years and deviations according to the analysis of tumor markers; Signed voluntary informed consent to participate in the study. Exclusion Criteria: Coronary artery disease, previously undergone cardiac surgery, including stenting of the coronary arteries; The presence of clinically significant valve pathology, blood clots in the cavities of the heart, aneurysms of the left ventricle, hypertrophic, early postpartum, alcoholic or restrictive cardiomyopathy, congenital heart defects and resistant hypertension; A history of stroke in the past 2 years; A history of autoimmune and immunodeficiency diseases; Polyvalent allergy; Decompensation of concomitant chronic diseases; Reception of systemic corticosteroids, cytostatics, immunosuppressive drug therapy (cyclophosphamide, methotrexate, cyclosporine, azathioprine, etc.), as well as drugs that deplete DNA or cytotoxic drugs, the last intake of which was within four weeks before the study; Hepatitis B and / or C, syphilis, HIV-carriage or AIDS; The presence of acute systemic infections requiring targeted antibiotic therapy; A history of untreated peptic ulcer and bleeding from the gastrointestinal tract; The presence of early transferred closed and open craniocerebral injuries that have a clinical manifestation and require specialized treatment; A history of uncontrolled epileptic seizures; Porphyria; The need for hospitalization and treatment in a hospice; Alcohol and drug abuse, lack of permanent residence, severe depression, disorientation, distant living.

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Main Group<br>Patients of the main group will undergo cardiac catheterization with intracoronary administration of 1×10 (7) umbilical cord-derived mesenchymal stromal cells and and will continue to receive optimal pharmacological therapy | Procedure: Cardiac catheterization<br>* Catheterization of the right and left heart cavities<br>Biological: Intracoronary administration of the umbilical cord-derived mesenchymal stromal cells<br>* After performing cardiac catheterization, selective coronary angiography will be performed abruptly to assess the condition of the coronary canal by access through the right radial or common femoral artery on the right after 70 U/kg of heparin iv. Then 20 ml of the finished suspension (1×10(7) umbilical cord-derived mesenchymal stromal cells diluted in 20 ml of heparinized saline) will be administrated into the mouth of the left coronary artery (LCA) without occlusion of the vessel with a balloon catheter and without stopping the coronary blood flow. Cell injection will be carried out using a standard 6 Fr catheter for selective coronary angiography with perfusion for 10 minutes at a volume rate of 2 ml/min, thereby introducing 1×10(6) cells per minute<br>|
| Active Comparator: Control Group<br>Patients in the control group will only have cardiac catheterization and will continue to receive optimal pharmacological therapy | Procedure: Cardiac catheterization<br>* Catheterization of the right and left heart cavities<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in the contractile function of the heart | changes in the ejection fraction of the right and left ventricles evaluated by transthoracic echocardiography and computed tomography | 1,3,6 months | 
| change in the size of the heart | changes in the size of the right and left atrium, end diastolic and end systolic size of the right and left ventricles evaluated by transthoracic echocardiography and computed tomography | 1,3,6 months | 
| change in the volumes of the heart | changes in the volumes of the right and left atrium, end diastolic and end systolic volumes of the right and left ventricles evaluated by transthoracic echocardiography and computed tomography | 1,3,6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in the clinical condition evaluated by the Scale for Heart failure to Optimize Clinical Status | changes in the clinical condition evaluated by the Scale for Heart failure to Optimize Clinical Status (SHOCS). The SHOCS scale consists of 10 points. The maximum possible score is 20, and the minimum is 0. Higher scores indicate a worse or worsening clinical condition, while lower scores or decreasing scores indicate a better clinical condition. | 1,3,6 months | 
| change in the markers of myocardial dysfunction | changes in the markers of myocardial dysfunction of the serum level of amino-terminal pro-brain natriuretic peptide | 1, 3 and 6 months | 
| change in the in the 6-minute walk test | changes in the 6-minute walk test, defined as the changes in the distance of traveled | 1, 3 and 6 months | 
| change in the functional status | change in the functional status according to the New York Heart Association classification | 1, 3 and 6 months | 
| change in the quality of life evaluated by the questionnaire Short Form 12 Healthy Survey | change in the quality of life evaluated by the questionnaire Short Form 12 Healthy Survey (SF-12). The SF 12 questionnaire consists of 12 items. The low level of the quality of life corresponds to estimates of 36-47 points, average of 24-35 points, high of 12-23 points. | 1, 3 and 6 months | 
| change in the quality of life evaluated by the Kansas City Cardiomyopathy Questionnaire | changes in the quality of life evaluated by the Kansas City Cardiomyopathy Questionnaire (KCCQ). The KCCQ is composed of 23 items. The options for the answers are of 1 to 5, 6 or 7 points and the score of each of its dimensions has a theoretical range from 0 to 100, 100 being the best outcome. | 1, 3 and 6 months | 
| change in the quality of life evaluated by the Minnesota Living with Heart Failure Questionnaire | changes in the quality of life evaluated by the Minnesota Living with Heart Failure (MLHF) Questionnaire. The MLHF questionnaire is composed of 21 items. The maximum possible scores being 105 and the minimum 0. Higher scores indicate a worse or worsening quality of life, while lower scores or decreasing scores indicate a better quality of life. | 1, 3 and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic heart failure, Non-ischemic Cardiomyopathy, Non-ischemic Dilated Cardiomyopathy, Mesenchymal stromal cells, Umbilical cord, Regenerative Medicine