Clinical trial NCT04011059: Randomized Study of Coronary Revascularization Surgery With Injection of WJ-MSCs and Placement of an Epicardial Extracellular Matrix
Official title: Randomized Study as Proof of Concept of Coronary Revascularization Surgery With Injection of Wharton's Jelly-derived Mesenchymal Cells and Placement of an Epicardial Extracellular Matrix Patch Seeded With WJ-MSCs in Patients With Ischemic Cardiomyopathy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Cardiovascular Diseases
Heart Failure
Coronary Artery Disease
Mesenchymal Stem Cell Transplantation
Regenerative Medicine
Keywords: Heart Failure
Cardiomyopathies
Coronary Artery Disease
Ischemic Dilated Cardiomyopathy
Lead sponsor: Hospital San Vicente Fundación
Sponsor class: OTHER
Collaborators: name: Instituto Colombiano para el Desarrollo de la Ciencia y la Tecnología (COLCIENCIAS)
name: IPS Universitaria Servicios de Salud Universidad de Antioquia
name: Hospital San Vicente Fundación - Rionegro
First posted: 2019-07-08
Enrollment: 40
Sex: ALL
Minimum age (years): 30
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A randomized clinical trial will be conducted as a proof of concept in 40 patients with previous myocardial infarction and a viable myocardial zone with indications for coronary artery bypass grafts. Twenty patients will be included in each treatment arm over 36 months. One group will undergo revascularization surgery, extracellular matrix patch placement and injection of cell culture medium; the other group will undergo revascularization surgery, extracellular matrix patch placement on the epicardial surface with cultured WJ-MSCs and injection of WJ-MSCs around the infarcted zone.

The allocation of treatments will be defined by block sizes of 2, 4 and 6, randomly determined by a random number generator (ralloc, Stata Co. 8,2). This assignment will only be known by the tissue bank that will deliver the syringes with the solution to be administered and the epicardium patches to the study participants.
Primary purpose: TREATMENT

Brief summary: Ischemic heart disease is one of the most important causes of mortality and morbidity in the Western world and is a public health problem. Among ischemic heart diseases, myocardial infarction has specific significance because the cardiac muscle does not have sufficient and adequate capacity to regenerate; therefore, necrosis of a region leads to the formation of a fibrous scar. Infarction can lead to a progressive and irreversible decrease in cardiac function, resulting in heart failure (HF) syndrome, depending on the area affected by this scar, via a ventricular remodeling mechanism.

In recent years, HF has been revealed as a major public health problem due to its incidence and its social, economic and especially human impact, as it represents a serious limitation of the quality of life of individuals. The prevalence of HF in the general population of the United States and the United Kingdom is approximately 1%, and in those older than 75 years, the prevalence varies between 5 and 10%. Regarding its prognosis, recent data from the Framingham Study indicate that at 5 years, the mortality rate of HF is 75% in men and 62% in women; the mean mortality rate of all cancers is 50%.

The molecular basis of congestive HF is the absence of cardiac cells capable of regenerating the heart muscle. Despite the publication of recent studies suggesting the existence of stem cells capable of regenerating cardiomyocytes destroyed because of myocardial infarction, in humans, the capacity of these cells is insufficient to replace the cells destroyed due to necrosis secondary to ischemia.

In recent years, the accumulation of results derived from preclinical studies has allowed the development of the first clinical trials of the feasibility and safety of cardiac regeneration using cellular therapy. Several studies have shown that t cells exist in adult bone marrow, such as mesenchymal stem cells, hematopoietic stem cells and, more recently, multipotent stem cells (MAPC), with the ability to differentiate into endothelial tissue and cardiac muscle, which can contribute to the regeneration of damaged myocardial tissue and improve cardiac function in animal infarction models. However, cell therapy research has moved rapidly toward the use of more undifferentiated cells rather than hematopoietic lineages, such as mesenchymal cells. These cells can be obtained from different sources, with a tendency toward the use of characterized allogeneic cells, which are immediately available in the potential recipient. Given that this type of therapy has not been rigorously investigated in Latin America, we aim to determine the effect of therapy using Wharton's jelly-derived mesenchymal cells (WJ-MSCs) from the human umbilical cord on neomyogenesis in patients with previous myocardial infarction who are undergoing open revascularization. Our hospital has some experience with regenerative therapy, both in patients with acute myocardial infarction and chronic infarction, with encouraging results that support this new phase of inter-institutional research.

Objective: To evaluate the safety and estimate the effect of coronary revascularization accompanied by intramyocardial injection of WJ-MSCs and the placement of an extracellular matrix patch seeded with WJ-MSCs compared to coronary revascularization accompanied by injection of culture medium without the presence of WJ-MSC and placement of an extracellular matrix patch without seeding with WJ-MSC on global and regional cardiac function, myocardial viability and the incidence of adverse effects determined as ventricular arrhythmias.

Detailed description: A randomized clinical trial will be conducted as a proof of concept in 40 patients with previous myocardial infarction and a viable myocardial zone with indications for coronary artery bypass grafts. Twenty patients will be included in each treatment arm over 36 months. One group will undergo revascularization surgery, extracellular matrix patch placement and injection of cell culture medium; the other group will undergo revascularization surgery, extracellular matrix patch placement on the epicardial surface with cultured WJ-MSCs and injection of WJ-MSCs around the infarcted zone.

The allocation of treatments will be defined by block sizes of 2, 4 and 6, randomly determined by a random number generator (ralloc, Stata Co. 8,2). This assignment will only be known by the tissue bank that will deliver the syringes with the solution to be administered and the epicardium patches to the study participants.

Eligibility criteria: Inclusion Criteria:

* Patients with a diagnosis of coronary disease, performed by coronary angiography, requiring conventional coronary revascularization surgery
* History of myocardial infarction; evidence of akinesia or regional dyskinesia more than 1 week old
* Ejection fraction less than 40%
* Age between 30 and 75 years
* Negative serology for HIV, hepatitis B virus (HBV), and hepatitis C virus HCV
* Negative pregnancy test for women of childbearing age
* Patients who sign the informed consent complying with all of the provisions of current regulations in Colombia

Exclusion Criteria:

* History of myocardial infarction with ST-segment elevation within 2 weeks prior to surgery
* History of myocardial infarction without ST-segment elevation within the previous week (the decision to include these patients within the first week after suffering a non-ST elevation infarction is at the discretion of the research team)
* Previous history of tachycardia or ventricular fibrillation
* History of active neoplasia or previous chemotherapy treatment
* Severe or uncontrolled concomitant disease (i.e., poorly controlled chronic kidney or liver failure)
* Patients who, due to their place of residence, mental health or social situation, have difficulty meeting the conditions of the protocol
* Women who are pregnant or breast-feeding
* Patients or legal representatives withdrawing informed consent at any time during the study.
* Previous history of heart transplant
* Patients with functional organ impairment: liver function: total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase greater than 2 times the upper reference limit; kidney function: serum creatinine \> 1.5 mg/dl or creatinine clearance \< 60 ml/min.

Primary outcomes:
measure: Left ventricular ejection fraction (LVEF)
timeFrame: 12 months
measure: Final diastolic and systolic volumes
timeFrame: 12 months
measure: Left ventricule viability
timeFrame: 12 months
measure: Ventricular arrhythmias
timeFrame: 12 months
Secondary outcomes:
measure: Estimated functional status
timeFrame: 12 months
measure: Change in the median score of Quality of life
timeFrame: 12 months
measure: Delayed enhancement of the left ventricle
timeFrame: 12 months
measure: Improvement in the 6-minute walk test
timeFrame: 12 months
measure: Mortality at 3 and 12 months due to cardiovascular causes
timeFrame: 12 months
measure: Mortality at 3 and 12 months due to all causes
timeFrame: 12 months
Other outcomes:
Locations:
city: Medellín
country: Colombia
facility: Hospital San Vicente Fundación
state: Antioquia
Study officials:
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