Pericardial Matrix With Mesenchymal Stem Cells for the Treatment of Patients With Infarcted Myocardial Tissue (PERISCOPE)

Pericardial Matrix With Mesenchymal Stem Cells for the Treatment of Patients With Infarcted Myocardial Tissue (The PERISCOPE Trial)

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.

Study Overview

• Status: Completed
• Conditions: Myocardial Infarction
• Intervention / Treatment: Combination product: PeriCord: Expanded and cryopreserved allogeneic umbilical cord Wharton´s jelly-derived adult mesenchymal stem cells colonized on human pericardial matrix.; Procedure: Surgery by sternotomy

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitari Germans Trias i Pujol

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 97 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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 (PeriCord) construct will be placed on the ischemic area of the non-candidate revascularization area and will be fixed using surgical glue. PeriCord: Expanded and cryopreserved allogeneic umbilical cord Wharton´s jelly-derived adult mesenchymal stem cells colonized on human pericardial matrix .	Combination product: PeriCord: Expanded and cryopreserved allogeneic umbilical cord Wharton´s jelly-derived adult mesenchymal stem cells colonized on human pericardial matrix.; A matrix-cell construct (PeriCord) will be placed on the ischemic area of the non-candidate revascularization area during a surgery by sternotomy to perform the surgical revascularization of the arteries candidates for revascularization.
Active Comparator: 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.	Procedure: Surgery by sternotomy; The patient will undergo surgery by sternotomy to perform the surgical revascularization of the arteries candidates for revascularization. No additional procedure will be performed only the by-pass.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of death or rehospitalization due to any cause and / or adverse reactions related to the procedure / product under investigation.	Safety measured with a combined endpoint of serious clinical events (death or rehospitalization due to any cause) and serious adverse reactions related to the investigational treatment.	at 12 months of follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of death or rehospitalization due to any cause and / or adverse reactions related to the procedure / product under investigation.	Safety measured with a combined endpoint of serious clinical events (death or rehospitalization due to any cause) and serious adverse reactions related to the investigational treatment	At 1 week, 3 and 6 months
Death rate or rehospitalization due to cardiovascular causes	Death rate or rehospitalization due to cardiovascular causes at week, 3, 6 and 12 months.	At 1 week, 3 , 6and 12 months
Rate of relevant arrhythmias in Holter of 24 hours	Rate of relevant arrhythmias in Holter of 24 hours a week, 3 and 12 months.	At 1 week, 3 and 12 months
Relevant changes in N-terminal B-type natriuretic peptide (NT-proBNP) and High sensitivity troponin I (hsTnI) levels	Relevant changes in NT-proBNP and hsTnI levels at week, 3 and 12 months.	At 1 week, 3 and 12 months
Changes in the necrotic myocardial mass ratio	Changes in the necrotic myocardial mass ratio due to gadolinium retention at 3 and 12 months.	At 3 and 12 months
Changes of regional contractility	change of regional contractility by nuclear magnetic resonance (NMR) at 3 and 12 months.	At 3 and 12 months
Changes in ejection fraction of the left ventricle	Changes in ejection fraction of the left at 3 and 12 months	At 3 and 12 months
changes in left and right ventricular geometric remodeling	changes in left and right ventricular geometric remodeling at 3 and 12 months	At 3 and 12 months
Changes in the score on the quality of life test Short Form 36 Healthy Survey (SF-36).	Changes in the score on the quality of life test SF-36 will be used at 3 and 12 months. The mínimum value is 0 and the máximum value is 100. Higher scores mean a better outcome.	At 3 and 12 months
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.	Changes in the score on the quality of life test KCCQ in cases of participants with heart failure will be used at 3 and 12 months. The test is composed of 23 items. The options for the answers are Likert scales 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.	At 3 and 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
monocyte populations and cytokines and chemokines levels	changes in the monocyte populations and cytokines and chemokines levels between the two groups in order to analyze if the PeriCord could improve these variables	At screening, day 3 and day 5

Collaborators and Investigators

• Sponsor: Fundació Institut Germans Trias i Pujol
• Collaborators: Germans Trias i Pujol Hospital
• Investigators: Principal Investigator: Antoni Bayes-Genís, MD, PhD,FESC, Institut del Cor, HUGTiP, IGTP

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2019
• Primary Completion (Actual): September 27, 2022
• Study Completion (Actual): October 6, 2022

Study Registration Dates

• First Submitted: December 21, 2018
• First Submitted That Met QC Criteria: January 8, 2019
• First Posted (Actual): January 9, 2019

Study Record Updates

• Last Update Posted (Actual): December 2, 2022
• Last Update Submitted That Met QC Criteria: December 1, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Clinical trial; Cell therapy; Tissue engineering; Wharton jelly mesenchymal stem cells; Cardiac repair; Chronic myocardial infarction
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction
• Other Study ID Numbers: ICOR-2016-02; 2018-001964-49 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No