Clinical trial NCT02368587: Intracoronary or Intravenous Infusion Human Wharton' Jelly-derived Mesenchymal Stem Cells in Patients With Ischemic Cardiomyopathy
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
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Ischemic Cardiomyopathy
Keywords: intracoronary infusion
intravenous infusion
Wharton's jelly-derived mesenchymal stem cells
ischemic Cardiomyopathy
heart function
Lead sponsor: Navy General Hospital, Beijing
Sponsor class: OTHER
Collaborators: name: First People's Hospital of Foshan
name: General Hospital of Armed Police, Beijing
name: PLA General Hospital, Beijing
First posted: 2015-02-23
Enrollment: 160
Sex: ALL
Minimum age (years): 17
Maximum age (years): 90
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Age no limited
2. Patient must provide written informed consent.
3. 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.
4. 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
5. left ventricular ejection fraction (LVEF)\<45% by echocardiogram, CMRI, or left ventriculogram within the prior 6 m
6. 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:

1. Have a baseline glomerular filtration rate \> 50 mL/min per 1.73 m2
2. Evidence of a life-threatening arrhythmia (ventricular tachycardia or complete heart block) on screening ECG..
3. Have a hematologic abnormality as evidenced by hematocrit \<25% , white blood cell \<2500/u L or platelet values\<100000/u L without another explanation.
4. Have liver dysfunction , as evidenced by enzymes (aspartate aminotransferase and alanine aminotransferase) \>3× the upper limits of normal.
5. Have a coagulopathy (international normalized ratio \> 1.3) not because of a reversible cause (ie, coumadin).
6. Have a contraindication to performance of CMRI (CMRIs will be performed in patients with pacemaker who are not pacemaker dependent).
7. Be an organ transplant recipient.
8. Have a clinical history of malignancy within 5 y except curatively treated basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma.
9. Have a noncardiac condition that limits lifespan to \<1y.
10. Have a history of drug or alcohol abuse within the past 24 m.
11. Be serum positive for human immunodeficiency virus, hepatitis B surface antigen, or hepatitis C.
12. Be a female who is pregnant, nursing, or of childbearing potential who is not practicing effective contraceptive methods.

Primary outcomes:
measure: The primary end point was safety in incidence of adverse events (AEs) within 12 months
timeFrame: 12 months
Secondary outcomes:
measure: The secondary end point was efficacy in absolute change of the global LV ejection fraction (LVEF) from baseline to 12 months by MRI
timeFrame: 12 months
Other outcomes:
Locations:
Study officials:
affiliation: Navy General Hospital, Beijing
name: Ning K Zhang, MS
role: STUDY_DIRECTOR
References: