Timing for Bone Marrow Mononuclear Cells After Acute Myocardial Infarction

Timing for Intracoronary Administration of Bone Marrow Mononuclear Cells After Acute ST-elevated Myocardial Infarction: a Pilot Study

Most studies on intracoronary bone marrow mononuclear cell (BMC) transplantation for acute myocardial infarction (AMI) involve treatment 3-7 days after primary percutaneous coronary intervention (PCI); however, the optimal timing is unknown. The present study assessed the therapeutic effect at different times after ST-elevation myocardial infarction (STEMI).

Study Overview

• Status: Completed
• Conditions: Myocardial Infarction
• Intervention / Treatment: Other: BMC therapy within 24 hours; Other: BMC therapy within 3-7 days; Other: BMC therapy within 7-30 days; Other: PCI only

Detailed Description

On the basis of experimental studies that bone marrow mononuclear cells (BMCs) transfer in the injured tissue can promote regional myocardial perfusion and improved cardiac function, several clinical trials have shown that intracoronary bone marrow mononuclear cell (BMC) transplantation in acute myocardial infarction (AMI) patients several days after myocardial reperfusion is safe and may enhance the improvement of left ventricular ejection fraction (LVEF). The timing of BMC administration, baseline LVEF, dosage of BMC and other factors has been linked to improvement in LVEF after BMC transplantation. In our previous work, we gave BMCs within 24 hours after emergency percutaneous coronary intervention (PCI) and found that it was safe and effective . In addition, there are another report about longer time from symptom onset to BMC infusion (2-4 weeks), which also appeared effective . The timing of intracoronary stem cell administration may have a critical effect on cell engraftment and may be responsible for the various biological and functional responses to therapy. However, few studies have directly addressed the optimal timing of cell injections. Therefore, in this prospective randomized study, BMCs were given at different times (within 24 hours, 3 to 7 days, or 7 to 30 days after reperfusion) to investigate whether the timing of therapy affects the therapeutic response of AMI patients.

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Phase 2; Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• a history of first acute ST-elevation myocardial infarction
• treatment with successful PCI two to twelve hours after symptom onset
• LVEF less than 50% on angiography immediately after emergency PCI or rescue PCI

Exclusion Criteria:

• previous Q-wave myocardial infarction
• cardiogenic shock
• severe coexisting conditions such as acute and chronic heart failure, malignant
• arrhythmia, renal failure and severe bleeding that interfered with the ability of the
• patient to comply with the protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BMC therapy within 24 hours; Patients with acute myocardial infarction who receive intracoronary infusion of BMC within 24 hours after successful primary PCI.	Other: BMC therapy within 24 hours; The BMCs were isolated by Ficoll density gradient centrifugation on Lymphocyte Separation Medium. BMCs were infused into IRA at the site of the previous occlusion. This was accomplished with the use of a microtubular. After positioning of the microtubular into the distal segment vessel of the stent position in the infarct-related artery, 15 milliliter of the whole cell suspension was slowly administered via microtubular. The usual time should be over 10min to prevent back-flow and to prolong cellular contact time for cellular migration into the tissue. Patients in BMC therapy group within 24 hours remained in the cath-lab until the entire procedure, including primary PCI and intracoronary BMC infusion, was completed.
Experimental: BMC therapy within 3-7 days; Patients with acute myocardial infarction who receive intracoronary infusion of BMC within 3-7days after successful primary PCI.	Other: BMC therapy within 3-7 days; Patients in this group, who underwent a second procedure, to receive BMC transplantation in the cath-lab during the same hospitalization or returned for a second hospitalization.
Experimental: BMC therapy within 7-30 days; Patients with acute myocardial infarction who receive intracoronary infusion of BMC within 7-30days after successful primary PCI.	Other: BMC therapy within 7-30 days; Patients in this group, who underwent a second procedure, to receive BMC transplantation in the cath-lab during the same hospitalization or returned for a second hospitalization.
Active Comparator: PCI only; Patients with acute myocardial infarction who were performed successful primary PCI.	Other: PCI only; The saline was intracoronary infusion with the use of microtubular.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change of left ventricular eject factor (LVEF) from the baseline	12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Change of left ventricular end-diastolic volume (LVESV) from the baseline	12 months
Change of left ventricular end-systolic volume (LVEDV) from the baseline	12 months
Change of myocardial perfusion from the baseline	12 months

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Dalian Medical University
• Collaborators: Fudan University

Publications and helpful links

General Publications

• Yao K, Huang R, Sun A, Qian J, Liu X, Ge L, Zhang Y, Zhang S, Niu Y, Wang Q, Zou Y, Ge J. Repeated autologous bone marrow mononuclear cell therapy in patients with large myocardial infarction. Eur J Heart Fail. 2009 Jul;11(7):691-8. doi: 10.1093/eurjhf/hfp062. Epub 2009 May 6.
• Yao K, Huang R, Qian J, Cui J, Ge L, Li Y, Zhang F, Shi H, Huang D, Zhang S, Sun A, Zou Y, Ge J. Administration of intracoronary bone marrow mononuclear cells on chronic myocardial infarction improves diastolic function. Heart. 2008 Sep;94(9):1147-53. doi: 10.1136/hrt.2007.137919. Epub 2008 Apr 1.
• Huang R, Yao K, Sun A, Qian J, Ge L, Zhang Y, Niu Y, Wang K, Zou Y, Ge J. Timing for intracoronary administration of bone marrow mononuclear cells after acute ST-elevation myocardial infarction: a pilot study. Stem Cell Res Ther. 2015 May 29;6(1):112. doi: 10.1186/s13287-015-0102-5.

Study record dates

Study Major Dates

• Study Start: February 1, 2005
• Primary Completion (Actual): August 1, 2006
• Study Completion (Actual): August 1, 2006

Study Registration Dates

• First Submitted: April 15, 2015
• First Submitted That Met QC Criteria: April 23, 2015
• First Posted (Estimate): April 24, 2015

Study Record Updates

• Last Update Posted (Estimate): April 24, 2015
• Last Update Submitted That Met QC Criteria: April 23, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: cell therapy; timing; BMC
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction
• Other Study ID Numbers: 2004BA714B05-2