Back to resultsIntracoronary or Intravenous Infusion Human Wharton' Jelly-derived Mesenchymal Stem Cells in Patients With Ischemic Cardiomyopathy (WJ-ICMP Tria)
Primary Purpose
Ischemic Cardiomyopathy
Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
WJMSCs Vs. placebo
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Ischemic Cardiomyopathy focused on measuring intracoronary infusion, intravenous infusion, Wharton's jelly-derived mesenchymal stem cells, ischemic Cardiomyopathy, heart function
Eligibility Criteria
Inclusion Criteria:
- Age no limited
- Patient must provide written informed consent.
Have a diagnosis of chronic ischemic left ventricular dysfunction secondary to myocardial infarction (MI) as defined by any of the following 3 criteria:
- Previous MI is documented by a clinical history that includes an elevation of cardiac enzymes and/or electrocardiogram (ECG) changes consistent with MI.
- Patients treated with thrombolytic therapy or percutaneous coronary revascularization.
- Screening CMRI shows an area of akinesis, dyskinesis, or severe hypokinesis associated with evidence of myocardial scarring based on delayed hyperenhancement after gadolinium infusion.
- Patient has been treated with appropriate maximal medic al therapy for ICMP. For β -blockade, the patient must have be en on a stable dose of a clinically appropriate β-blocker for 3 months. For angiotensin-converting enzyme inhibition, the patient must have been on a stable dose of a clinically appropriate agent for 1 m
- left ventricular ejection fraction (LVEF)<45% by echocardiogram, CMRI, or left ventriculogram within the prior 6 m
- Patients who are a candidate for cardiac catheterization assignment intracoronary infusion group; but patients in no-candidate for cardiac catheterization assignment intravenous infusion group.
Exclusion Criteria:
- Have a baseline glomerular filtration rate > 50 mL/min per 1.73 m2
- Evidence of a life-threatening arrhythmia (ventricular tachycardia or complete heart block) on screening ECG..
- Have a hematologic abnormality as evidenced by hematocrit <25% , white blood cell <2500/u L or platelet values<100000/u L without another explanation.
- Have liver dysfunction , as evidenced by enzymes (aspartate aminotransferase and alanine aminotransferase) >3× the upper limits of normal.
- Have a coagulopathy (international normalized ratio > 1.3) not because of a reversible cause (ie, coumadin).
- Have a contraindication to performance of CMRI (CMRIs will be performed in patients with pacemaker who are not pacemaker dependent).
- Be an organ transplant recipient.
- Have a clinical history of malignancy within 5 y except curatively treated basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma.
- Have a noncardiac condition that limits lifespan to <1y.
- Have a history of drug or alcohol abuse within the past 24 m.
- Be serum positive for human immunodeficiency virus, hepatitis B surface antigen, or hepatitis C.
- Be a female who is pregnant, nursing, or of childbearing potential who is not practicing effective contraceptive methods.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Placebo Comparator
Arm Label
Intracoronary infusion WJMSCs
Intravenous infusion WJMSCs
Arm Description
Intracoronary infusion WJMSCs or placebo in patients with ischemic heart failure
Intravenous infusion WJMSCs or placebo in patients with ischemic heart failure.
Outcomes
Primary Outcome Measures
The primary end point was safety in incidence of adverse events (AEs) within 12 months
the incidence of adverse events (AEs) within 12 months, including death, nonfatal MI, stroke, hospitalization for worsening heart function, severe arrhythmias, repeated coronary intervention, stent thrombosis, coronary artery microvascular obstruction, immune system disorders, or ectopic tissue formation, was monitored and quantified. Laboratory assays, including biochemical assays, hematologic, tumor and immune indexes and Holter monitoring, were performed at the different follow-up times at 1 months-1 year. The trial will be monitored by a Data and Safety Monitoring Board (DSMB) and the trial will be discontinued in case of safety concerns.
Secondary Outcome Measures
The secondary end point was efficacy in absolute change of the global LV ejection fraction (LVEF) from baseline to 12 months by MRI
The secondary end point was efficacy, which was assessed in terms of the absolute change in the global LV ejection fraction (LVEF) from baseline to 12 months post-treatment, as measured by cardiac magnetic resonance imaging (CMRI). Furthermore, CMRI assessments measured scar mass and viable myocardial mass in the left ventricle, scar size, cardiac volumes, global function, regional function, and 6-min walk tests in all patients from baseline to 12 months post-treatment.
Full Information
NCT ID
NCT02368587
First Posted
February 3, 2015
Last Updated
December 3, 2019
Sponsor
Navy General Hospital, Beijing
Collaborators
First People's Hospital of Foshan, General Hospital of Armed Police, Beijing, PLA General Hospital, Beijing
1. Study Identification
Unique Protocol Identification Number
NCT02368587
Brief Title
Intracoronary or Intravenous Infusion Human Wharton' Jelly-derived Mesenchymal Stem Cells in Patients With Ischemic Cardiomyopathy
Acronym
WJ-ICMP Tria
Official Title
Randomised, Double-blind, Placebo-controlled, Intracoronary or Intravenous Infusion Human Wharton' Jelly-derived Mesenchymal Stem Cells in Patients With Ischemic Cardiomyopathy
Study Type
Interventional
2. Study Status
Record Verification Date
December 2019
Overall Recruitment Status
Unknown status
Study Start Date
January 1, 2020 (Anticipated)
Primary Completion Date
January 1, 2021 (Anticipated)
Study Completion Date
July 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Navy General Hospital, Beijing
Collaborators
First People's Hospital of Foshan, General Hospital of Armed Police, Beijing, PLA General Hospital, Beijing
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to investigate the safety and efficacy of intracoronary or intravenous infusion human umbilical Wharton's jelly-derived Mesenchymal Stem Cell (WJMSC) in patients with ischemic cardiomyopathy secondary to myocardial infarction.
Detailed Description
Ischemic heart failure (IHF) secondary to myocardial infarction is a common, lethal, disabling, and expensive condition. Despite advances over the last 30 years, the prognosis of patients with IHF remains poor. At present, there has been increasing interest in attempting to repair the failing heart with the use of stem cells, since this approach has the potential to regenerate dead myocardium and thus alleviate the underlying cause of IHF.
A very primitive population of mesenchymal stem cells (MSCs) has been isolated from a continuum from the sub-amnion to perivascular region of umbilical cord, referred to as Wharton's jelly-derived MSCs (WJMSCs). WJMSCs retain a combination of most of their embryonic stem cell (ESC) and MSC markers in primary culture and early passages, thus retaining their multipotent stem cell characteristics. Preclinical studies have demonstrated that WJMSCs can be induced to differentiate into cardiomyocytes and endothelial cells and to integrate into the vasculature and ischemic cardiac tissue, as well as to improve heart function significantly. Therefore, the investigators performed a double-blind, placebo-controlled trial, randomly assigning 160 patients with ischemic heart failure secondary to myocardial infarction to receive an intracoronary or intravenous infusion of WJMSCs or placebo, to investigate the therapeutic safety and efficacy of WJMSCs in patients with ischemic cardiomyopathy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ischemic Cardiomyopathy
Keywords
intracoronary infusion, intravenous infusion, Wharton's jelly-derived mesenchymal stem cells, ischemic Cardiomyopathy, heart function
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
160 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Intracoronary infusion WJMSCs
Arm Type
Placebo Comparator
Arm Description
Intracoronary infusion WJMSCs or placebo in patients with ischemic heart failure
Arm Title
Intravenous infusion WJMSCs
Arm Type
Placebo Comparator
Arm Description
Intravenous infusion WJMSCs or placebo in patients with ischemic heart failure.
Intervention Type
Biological
Intervention Name(s)
WJMSCs Vs. placebo
Intervention Description
WJMSCs Vs. placebo
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
WJMSCs Vs. placebo
Primary Outcome Measure Information:
Title
The primary end point was safety in incidence of adverse events (AEs) within 12 months
Description
the incidence of adverse events (AEs) within 12 months, including death, nonfatal MI, stroke, hospitalization for worsening heart function, severe arrhythmias, repeated coronary intervention, stent thrombosis, coronary artery microvascular obstruction, immune system disorders, or ectopic tissue formation, was monitored and quantified. Laboratory assays, including biochemical assays, hematologic, tumor and immune indexes and Holter monitoring, were performed at the different follow-up times at 1 months-1 year. The trial will be monitored by a Data and Safety Monitoring Board (DSMB) and the trial will be discontinued in case of safety concerns.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
The secondary end point was efficacy in absolute change of the global LV ejection fraction (LVEF) from baseline to 12 months by MRI
Description
The secondary end point was efficacy, which was assessed in terms of the absolute change in the global LV ejection fraction (LVEF) from baseline to 12 months post-treatment, as measured by cardiac magnetic resonance imaging (CMRI). Furthermore, CMRI assessments measured scar mass and viable myocardial mass in the left ventricle, scar size, cardiac volumes, global function, regional function, and 6-min walk tests in all patients from baseline to 12 months post-treatment.
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
17 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age no limited
Patient must provide written informed consent.
Have a diagnosis of chronic ischemic left ventricular dysfunction secondary to myocardial infarction (MI) as defined by any of the following 3 criteria:
Previous MI is documented by a clinical history that includes an elevation of cardiac enzymes and/or electrocardiogram (ECG) changes consistent with MI.
Patients treated with thrombolytic therapy or percutaneous coronary revascularization.
Screening CMRI shows an area of akinesis, dyskinesis, or severe hypokinesis associated with evidence of myocardial scarring based on delayed hyperenhancement after gadolinium infusion.
Patient has been treated with appropriate maximal medic al therapy for ICMP. For β -blockade, the patient must have be en on a stable dose of a clinically appropriate β-blocker for 3 months. For angiotensin-converting enzyme inhibition, the patient must have been on a stable dose of a clinically appropriate agent for 1 m
left ventricular ejection fraction (LVEF)<45% by echocardiogram, CMRI, or left ventriculogram within the prior 6 m
Patients who are a candidate for cardiac catheterization assignment intracoronary infusion group; but patients in no-candidate for cardiac catheterization assignment intravenous infusion group.
Exclusion Criteria:
Have a baseline glomerular filtration rate > 50 mL/min per 1.73 m2
Evidence of a life-threatening arrhythmia (ventricular tachycardia or complete heart block) on screening ECG..
Have a hematologic abnormality as evidenced by hematocrit <25% , white blood cell <2500/u L or platelet values<100000/u L without another explanation.
Have liver dysfunction , as evidenced by enzymes (aspartate aminotransferase and alanine aminotransferase) >3× the upper limits of normal.
Have a coagulopathy (international normalized ratio > 1.3) not because of a reversible cause (ie, coumadin).
Have a contraindication to performance of CMRI (CMRIs will be performed in patients with pacemaker who are not pacemaker dependent).
Be an organ transplant recipient.
Have a clinical history of malignancy within 5 y except curatively treated basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma.
Have a noncardiac condition that limits lifespan to <1y.
Have a history of drug or alcohol abuse within the past 24 m.
Be serum positive for human immunodeficiency virus, hepatitis B surface antigen, or hepatitis C.
Be a female who is pregnant, nursing, or of childbearing potential who is not practicing effective contraceptive methods.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yu Chen, MD,PhD
Phone
18600310120
Email
yuchen911@hotmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Lian Ru Gao, MD
Phone
13381207121
Email
glianru668@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ning K Zhang, MS
Organizational Affiliation
Navy General Hospital, Beijing
Official's Role
Study Director
12. IPD Sharing Statement
Learn more about this trial
Intracoronary or Intravenous Infusion Human Wharton' Jelly-derived Mesenchymal Stem Cells in Patients With Ischemic Cardiomyopathy
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