Clinical trial NCT01291329: Intracoronary Human Wharton's Jelly- Derived Mesenchymal Stem Cells (WJ-MSCs) Transfer in Patients With Acute Myocardial Infarction (AMI)
Official title: Phase 2 Study of Intracoronary Human Wharton's Jelly- Derived Mesenchymal Stem Cells (WJ-MSCs) Transfer in Patients With ST-segment Elevation Acute Myocardial Infarction (AMI)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: ST-Elevation Myocardial Infarction
Keywords: stem cell
acute ST-Elevation Myocardial Infarction
Lead sponsor: Navy General Hospital, Beijing
Sponsor class: OTHER
Collaborators: name: Chinese PLA General Hospital
name: General Hospital of Chinese Armed Police Forces
name: First People's Hospital of Foshan
First posted: 2011-02-08
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: 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 human umbilical Wharton's jelly-derived mesenchymal stem cell (WJ-MSC) transfer in patients with ST-segment elevation acute myocardial infarction.

Detailed description: It has been demonstrated that MSCs have the potential to differentiate into cardiomyocytes both in vitro and in vivo. Several clinical trials have been performed using autologous bone marrow-derived MSCs, but the results of these trials have been unsatisfactory because of a low number of MSCs in older patients and in those with coronary heart disease. WJ-MSCs from the human umbilical cord matrix which are of epiblastic origin and contain both human embryonic stem cell (hESC) and human mesenchymal stem cell markers appear to have a number of important advantages: they do not raise ethical issues, are widely multipotent, are not tumorigenic, and are not immunogenetic. Because of a short population doubling time they can be rapidly scaled up in large numbers. We performed a double-blind, placebo-controlled, multicenter trial, randomly assigning 160 patients with acute ST-segment elevation myocardial infarction to receive an intracoronary infusion of WJ-MSCs or placebo medium into the infarct artery 4-7 days after successful reperfusion therapy.

Eligibility criteria: Inclusion Criteria:

1. Patients at least 18 years of age；
2. Patients with 1st acute ST-elevation myocardial infarction (AMI) who undergo successful primary percutaneous coronary intervention (PCI) thrombolysis in myocardial infarction (TIMI) flow grade 3, but have a substantial residual left ventricular regional wall-motion abnormality measured by 2-D echocardiography.
3. No contraindications to undergoing cell-therapy procedure within 1 weeks after AMI and PCI.
4. Hemodynamic stability-defined as no requirement for intra-aortic balloon pump or for inotropic or blood-pressure supporting medications.
5. Consent to protocol and agree to comply with all follow-up visits and studies.

Exclusion Criteria:

1. Presence of cardiogenic shock ( defined as systolic blood pressure \< 80 mmHg requiring intravenous pressors or intra-aortic balloon counterpulsation);
2. Major bleeding requiring blood transfusion after acute reperfusion treatment;
3. A history of leucopenia;
4. Thrombocytopenia;
5. Hepatic or renal dysfunction;
6. Evidence for malignant diseases;
7. Unwillingness to participate;

Primary outcomes:
measure: Quantify myocardium metabolic and perfusion measured by F-18-fluorodeoxyglucose (F-18-FDG) postremission tomography (PET) and 99 mTctetrofosmine single-photon (SPET), as well as global left ventricular ejection fraction measured by echocardiography.
timeFrame: 4 months- 1 year
Secondary outcomes:
measure: Secondary endpoints: safety will be determined by the assessment of major adverse coronary events (MACE).
timeFrame: 4 months-1year
Other outcomes:
Locations:
city: Beijing
country: China
facility: Fu Cheng Lu 6
Study officials:
affiliation: Cardiology Division of Navy General Hospital
name: Lian Ru Gao, MD
role: STUDY_CHAIR
References:
citation: 1.Monya Baker. How to fix a broken heart? Nature. 2009; 460:18-19. 2.Psaltis PJ, Zannettino A, Worthley SG. Mesenchymal stromal cells potential for cardiovascular repair. Stem cells.2008; 10:1634. 3.Deryl L, Mark LT, Weiss, et al. Concise review : wharton's jelly-derived cells are a primitive stromal cell population. Stem Cells. 2008 ; 26 :591-599. 4.Nekanti U, Rao VB, Bahirvani AG, Ta M, et al. Long-term Expansion and Pluripotent Marker Array Analysis of Wharton's Jelly-Derived Mesenchymal Stem Cells. Stem Cells and Dev. 2010; 19:117-130. 5.Chen MY, Lie PC, Li ZL. Endothelial differentiation of Wharton's jelly-derived mesenchymal stem cells in comparison with bone marrow-derived mesenchymal stem cells. Exp Hematol. 2009;37(5):629-40.. 6.Wu KH, Mo XM, Zhou, B. et al. Cardiac potential of stem cells from whole human umbilical cord tissue. Journal of Cellular Biochemistry. 2009; 107:926-932.
citation: Gao LR, Chen Y, Zhang NK, Yang XL, Liu HL, Wang ZG, Yan XY, Wang Y, Zhu ZM, Li TC, Wang LH, Chen HY, Chen YD, Huang CL, Qu P, Yao C, Wang B, Chen GH, Wang ZM, Xu ZY, Bai J, Lu D, Shen YH, Guo F, Liu MY, Yang Y, Ding YC, Yang Y, Tian HT, Ding QA, Li LN, Yang XC, Hu X. Intracoronary infusion of Wharton's jelly-derived mesenchymal stem cells in acute myocardial infarction: double-blind, randomized controlled trial. BMC Med. 2015 Jul 10;13:162. doi: 10.1186/s12916-015-0399-z.