The Application of the Umbilical Cord Mesenchymal Stem Cells in the Complex Treatment of Chronic Heart Failure of Non-ischemic Etiology (RegenHeart)

• ClinicalTrials.gov Identifier: NCT04325594
• Recruitment Status: Unknown
• First Posted: March 27, 2020
• Last Update Posted: March 27, 2020
• Sponsor: The Research-Clinical Center for Cardiac Surgery and Transplantology LLP
• Collaborator: State-Financed Health Facility "Samara Regional Medical Center Dinasty"
• Information provided by (Responsible Party): Azkhojayev Aziz, MD, The Research-Clinical Center for Cardiac Surgery and Transplantology LLP

Tracking Information

• First Submitted Date: March 3, 2020
• First Posted Date: March 27, 2020
• Last Update Posted Date: March 27, 2020
• Actual Study Start Date: March 1, 2020
• Estimated Primary Completion Date: October 31, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 26, 2020)

• change in the contractile function of the heart [ Time Frame: 1,3,6 months ]
  changes in the ejection fraction of the right and left ventricles evaluated by transthoracic echocardiography and computed tomography
• change in the size of the heart [ Time Frame: 1,3,6 months ]
  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
• change in the volumes of the heart [ Time Frame: 1,3,6 months ]
  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

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: March 26, 2020)

• change in the clinical condition evaluated by the Scale for Heart failure to Optimize Clinical Status [ Time Frame: 1,3,6 months ]
  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.
• change in the markers of myocardial dysfunction [ Time Frame: 1, 3 and 6 months ]
  changes in the markers of myocardial dysfunction of the serum level of amino-terminal pro-brain natriuretic peptide
• change in the in the 6-minute walk test [ Time Frame: 1, 3 and 6 months ]
  changes in the 6-minute walk test, defined as the changes in the distance of traveled
• change in the functional status [ Time Frame: 1, 3 and 6 months ]
  change in the functional status according to the New York Heart Association classification
• change in the quality of life evaluated by the questionnaire Short Form 12 Healthy Survey [ Time Frame: 1, 3 and 6 months ]
  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.
• change in the quality of life evaluated by the Kansas City Cardiomyopathy Questionnaire [ Time Frame: 1, 3 and 6 months ]
  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.
• change in the quality of life evaluated by the Minnesota Living with Heart Failure Questionnaire [ Time Frame: 1, 3 and 6 months ]
  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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: The Application of the Umbilical Cord Mesenchymal Stem Cells in the Complex Treatment of Chronic Heart Failure of Non-ischemic Etiology
• Official Title: 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
• Brief Summary: 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

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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Chronic Heart Failure
• Non-ischemic Cardiomyopathy
• Non-ischemic Dilated Cardiomyopathy

Intervention

• Procedure: Cardiac catheterization
  Catheterization of the right and left heart cavities
• Biological: Intracoronary administration of the umbilical cord-derived mesenchymal stromal cells
  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

Study Arms

• Experimental: Main Group
  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
  Interventions:

  • Procedure: Cardiac catheterization
  • Biological: Intracoronary administration of the umbilical cord-derived mesenchymal stromal cells
• Active Comparator: Control Group
  Patients in the control group will only have cardiac catheterization and will continue to receive optimal pharmacological therapy
  Intervention: Procedure: Cardiac catheterization

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: March 26, 2020): 60
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2020
• Estimated Primary Completion Date: October 31, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Kazakhstan

Administrative Information

• NCT Number: NCT04325594
• Other Study ID Numbers: RCCCT 02-02-2020
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Azkhojayev Aziz, MD, The Research-Clinical Center for Cardiac Surgery and Transplantology LLP
• Original Responsible Party: Same as current
• Current Study Sponsor: The Research-Clinical Center for Cardiac Surgery and Transplantology LLP
• Original Study Sponsor: Same as current
• Collaborators: State-Financed Health Facility "Samara Regional Medical Center Dinasty"

Investigators

• Principal Investigator: Aziz Azkhojayev, MD; The Research-Clinical Center for Cardiac Surgery and Transplantology LLP

• PRS Account: The Research-Clinical Center for Cardiac Surgery and Transplantology LLP
• Verification Date: March 2020