Clinical trial NCT04325594: The Application of the Umbilical Cord Mesenchymal Stem Cells in the Complex Treatment of Non-ischemic Heart Failure
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Chronic Heart Failure
Non-ischemic Cardiomyopathy
Non-ischemic Dilated Cardiomyopathy
Keywords: Chronic heart failure
Non-ischemic Cardiomyopathy
Non-ischemic Dilated Cardiomyopathy
Mesenchymal stromal cells
Umbilical cord
Regenerative Medicine
Lead sponsor: The Research-Clinical Center for Cardiac Surgery and Transplantology LLP
Sponsor class: OTHER
Collaborators: name: State-Financed Health Facility "Samara Regional Medical Center Dinasty"
First posted: 2020-03-27
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this prospective single-arm clinical study was to evaluate the safety and potential efficacy of intracoronary administration of allogeneic umbilical cord-derived mesenchymal stromal cells (MSCs) as an addition to standard medical therapy in patients with chronic non-ischemic heart failure.

Detailed description: This prospective, open-label, single-arm clinical trial investigated the safety and potential efficacy of intracoronary administration of allogeneic umbilical cord-derived mesenchymal stromal cells (MSCs) in patients with chronic non-ischemic heart failure.

A total of 30 patients were enrolled. All participants received standard pharmacological therapy and underwent a single intracoronary infusion of 1×10⁷ MSCs delivered into the left coronary artery during routine cardiac catheterization. The primary objective was to assess the safety of the cell therapy over the first 5 days of hospitalization. Secondary outcomes included changes in left ventricular ejection fraction (LVEF), end-diastolic and end-systolic volumes and diameters, serum NT-proBNP levels, NYHA functional class, 6-minute walk test distance, and quality of life indicators (SF-12, KCCQ, MLHFQ) at 1, 3, and 6 months post-infusion.

Although the study was originally registered with a control group and randomization, it was ultimately conducted as a single-arm design due to ethical and logistical constraints in recruitment. All patients received the same intervention, and no allocation or randomization was performed.

While most patients had clinical indications for an implantable cardioverter-defibrillator (ICD) in accordance with international guidelines, not all had the device implanted due to personal refusal of the procedure. Therefore, ICD presence was not required for inclusion in the study.

Although remuscularization of the myocardium was not a predefined endpoint, retrospective analysis revealed post-treatment thickening of the left ventricular posterior wall and interventricular septum in a subset of patients, as observed on cardiac computed tomography. This structural change was associated with improved systolic function and may guide future hypothesis-driven research.

Eligibility criteria: Inclusion Criteria:

* Men and women aged 18 years and older
* Registered at the Research-Clinical Center for Cardiac Surgery and Transplantology
* Established diagnosis of non-ischemic dilated cardiomyopathy (NYHA Class III-IV)
* Non-ischemic etiology confirmed by coronary angiography or contrast-enhanced cardiac CT
* Left ventricular ejection fraction (LVEF) ≤ 35% based on echocardiography or cardiac CT
* Clinical indications for implantation of an implantable cardioverter-defibrillator (ICD), regardless of actual implantation status
* No clinical or laboratory signs of dysfunction or insufficiency of other major organs
* No history of malignancy within the past 5 years and no abnormal tumor markers
* Signed written informed consent

Exclusion Criteria:

* Ischemic heart disease or prior cardiac surgery, including coronary artery stenting
* Significant valvular heart disease, intracardiac thrombus, left ventricular aneurysm, hypertrophic, postpartum, alcoholic or restrictive cardiomyopathy, congenital heart defects, or resistant hypertension
* Stroke within the past 2 years
* Autoimmune or immunodeficiency disorders
* Polyvalent allergy
* Decompensated chronic comorbidities
* Use of systemic corticosteroids, cytotoxic or immunosuppressive drugs (e.g., cyclophosphamide, methotrexate, cyclosporine, azathioprine) within 4 weeks before enrollment
* Positive tests for hepatitis B or C, syphilis, or HIV/AIDS
* Active systemic infections requiring targeted antibiotic therapy
* Untreated peptic ulcer disease or history of gastrointestinal bleeding
* Clinically significant traumatic brain injury requiring treatment
* Uncontrolled epileptic seizures
* Porphyria
* Requirement for hospice-level care
* Alcohol or drug abuse, lack of permanent residence, severe depression, disorientation, or inability to participate in follow-up

Primary outcomes:
measure: Incidence of ischemic and arrhythmic events, abnormal laboratory and ECG findings within 5 days after intracoronary infusion of umbilical cord-derived MSCs [Safety Assessment]
timeFrame: First 5 days after infusion
Secondary outcomes:
measure: Change in left ventricular structure and function
timeFrame: 1, 3, and 6 months
measure: Change in NT-proBNP levels
timeFrame: 1, 3, and 6 months
measure: Change in 6-minute walk test distance
timeFrame: 1, 3, and 6 months
measure: Change in NYHA functional class
timeFrame: 1, 3, and 6 months
measure: Change in quality of life
timeFrame: 1, 3, and 6 months
Other outcomes:
Locations:
city: Taraz
country: Kazakhstan
facility: The Research-Clinical Center for Cardiac Surgery and Transplantology LLP
state: Zhambyl
Study officials:
affiliation: The Research-Clinical Center for Cardiac Surgery and Transplantology LLP
name: Aziz Azkhojayev, MD
role: PRINCIPAL_INVESTIGATOR
References: