Clinical trial NCT03798353: Pericardial Matrix With Mesenchymal Stem Cells for the Treatment of Patients With Infarcted Myocardial Tissue
Official title: Pericardial Matrix With Mesenchymal Stem Cells for the Treatment of Patients With Infarcted Myocardial Tissue (The PERISCOPE Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Myocardial Infarction
Keywords: Cardiac repair
Wharton jelly mesenchymal stem cells
Chronic myocardial infarction
Tissue engineering
Cell therapy
Clinical trial
Lead sponsor: Fundació Institut Germans Trias i Pujol
Sponsor class: OTHER
Collaborators: name: Germans Trias i Pujol Hospital
First posted: 2019-01-09
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: - Experimental group: The patient will undergo surgery by sternotomy to perform the surgical revascularization of the arteries candidates for revascularization.

In addition, the matrix-cell construct will be placed on the ischemic area of the non-candidate revascularization area and will be fixed using surgical glue.

- Control group: The patient will undergo surgery by sternotomy to perform the surgical revascularization of the arteries candidates for revascularization. No additional procedure will be performed.
Primary purpose: TREATMENT

Brief summary: Myocardial infarction causes necrosis of myocardial cells and reduces cardiac function. Today, there are treatments such as primary angioplasty and thrombolysis that are effective in limiting cell death after acute myocardial infarction. However, the post-infarct scar often conditions a global ventricular remodeling that can evolve clinically towards heart failure and in more advanced stages the only therapy that completely restores cardiac function is heart transplantation.

Mesenchymal stem cells are multipotent cells found from embryonic mesoderm and found in all tissues. In the field of cardiac regeneration, studies have shown a certain degree of benefit when treated with MSCs from different origins. Our approach is based on a decellularized matrix that carries the cells directly over myocardial infarction.

Detailed description: Myocardial infarction causes necrosis of myocardial cells and reduces cardiac function. Today there are treatments such as primary angioplasty and thrombolysis that are effective in limiting cell death after acute myocardial infarction. However, the post-infarct scar often conditions a global ventricular remodeling that can evolve clinically towards heart failure and, in more advanced stages, the only therapy that completely restores cardiac function is heart transplantation.

Experimental studies are evaluating new therapeutic approaches based on tissue engineering for myocardial regeneration. Cardiac tissue engineering attempts to create functional tissue constructs that can restore the structure and function of damaged myocardium.

Mesenchymal stem cells (MSCs) are multipotent cells that develop from embryonic mesoderm and are found in all structural tissues of the body.

In the field of cardiac regeneration, studies have shown a certain degree of benefit when treated with MSCs from different origins. The investigators approach is based on a decellularized matrix that carries the cells directly over myocardial infarction.

Among the different types of MSC currently available, the investigators propose the use of those derived from the connective tissue surrounding the great vessels (2 arteries and one vein) of the umbilical cord called Wharton's gelatin (MSC, WJ) whose immunomodulatory properties are described extensively in the literature. These MSC, WJ cells have a PEI approved by the Spanish Agency for Medicines and Healthcare Products (AEMPS) (PEI 16-017) that guarantees an optimal manufacturing process for a clinical trial.

Eligibility criteria: Inclusion Criteria:

* Myocardial infarction of ≥50% of transmurally due to MR
* Candidate for coronary by-pass through that or another territory
* Age ≥18 years
* Signature of informed consent
* Wave Q present in the ECG
* Followed by the cardiology service of Germans Trial i Pujol hospital

Exclusion Criteria:

* Severe valvular disease with indication of surgical repair
* Candidate for ventricular remodeling
* Contraindication for MR (creatinine clearance less than 30 ml / min / 1.73m2, metallic implant carriers, claustrophobia)
* Extracardiac disease with estimated life expectancy less than 1 year
* Neoplastic disease detected in the last five years or without complete remission
* Severe renal or hepatic insufficiency
* Abnormal laboratory values, not explainable at the time of inclusion, and that at the discretion of the investigator contraindicate the patient's participation in the study
* Patients with a previous cardiac intervention
* Women who are pregnant or breast-feeding.
* Women of childbearing age who are heterosexually active and who do not use an effective contraceptive method from 14 days before the inclusion in the study and at least up to 12 weeks after the end of the study.
* Simultaneous participation in another clinical trial or treatment with another product in investigational phase in the 30 days prior to inclusion in the study.
* Negation of the patient to be followed by a period that exceeds the clinical trial itself (long-term follow-up in the second and third year).

Primary outcomes:
measure: Rate of death or rehospitalization due to any cause and / or adverse reactions related to the procedure / product under investigation.
timeFrame: at 12 months of follow-up
Secondary outcomes:
measure: Rate of death or rehospitalization due to any cause and / or adverse reactions related to the procedure / product under investigation.
timeFrame: At 1 week, 3 and 6 months
measure: Death rate or rehospitalization due to cardiovascular causes
timeFrame: At 1 week, 3 , 6and 12 months
measure: Rate of relevant arrhythmias in Holter of 24 hours
timeFrame: At 1 week, 3 and 12 months
measure: Relevant changes in N-terminal B-type natriuretic peptide (NT-proBNP) and High sensitivity troponin I (hsTnI) levels
timeFrame: At 1 week, 3 and 12 months
measure: Changes in the necrotic myocardial mass ratio
timeFrame: At 3 and 12 months
measure: Changes of regional contractility
timeFrame: At 3 and 12 months
measure: Changes in ejection fraction of the left ventricle
timeFrame: At 3 and 12 months
measure: changes in left and right ventricular geometric remodeling
timeFrame: At 3 and 12 months
measure: Changes in the score on the quality of life test Short Form 36 Healthy Survey (SF-36).
timeFrame: At 3 and 12 months
measure: Changes in the score on the quality of life Kansas City Cardiomyopathy Questionnaire (KCCQ) test in cases of participants with heart failure will be used.
timeFrame: At 3 and 12 months
Other outcomes:
measure: monocyte populations and cytokines and chemokines levels
timeFrame: At screening, day 3 and day 5
Locations:
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
state: Barcelona
Study officials:
affiliation: Institut del Cor, HUGTiP, IGTP
name: Antoni Bayes-Genís, MD, PhD,FESC
role: PRINCIPAL_INVESTIGATOR
References: