Transplantation Efficacy of Autologous Bone Marrow Mesenchymal Stem Cells With Intensive Atorvastatin in AMI Patients (TEAM-AMI)

The Randomized Double-blind Placebo-Controlled Multi-center Clinical Trial of Transplantation Efficacy of Autologous Bone Marrow Mesenchymal Stem Cells With Intensive Atorvastatin in Acute Myocardial Infarction Patients

The benefit of current stem cell transplantation therapy for myocardial infarction is limited by low survival rate for stem cell. The purpose of this study is to test whether intensive Atorvastatin therapy can improve the outcome of patients with impaired left ventricle function after acute myocardial infarction who underwent intracoronary transfer of autologous bone marrow mesenchymal stem cells.

Study Overview

• Status: Unknown
• Conditions: Myocardial Infarction; Stem Cell Transplantation; Angioplasty, Transluminal, Percutaneous Coronary
• Intervention / Treatment: Drug: Atorvastatin; Drug: Low dose BMMSC; Drug: Middle dose BMMSC; Drug: High dose BMMSC; Drug: Transplantation; Drug: Intensive Atorvastatin

Detailed Description

The major challenge to a successful stem cell therapy for myocardial infarction is the low survival rate of implanted cells in the damaged tissue. Atorvastatin, an HMG-CoA reductase inhibitor, has multiple biological activities independent of cholesterol-lowering action.This study is performed to find out more information about the strategy with Atorvastatin therapy to improve the survival of implanted cells, autologous bone marrow mesenchymal stem cells transplantation. Patients between 30 and 75 years of age who receive autologous bone marrow mesenchymal stem cells transplant may be eligible for this study. These patients receive autologous bone marrow mesenchymal stem cells transplantation intracoronary undergoing Percutaneous Coronary Intervention with regular or high dose of Atorvastatin treatment. The objective evaluations will be performed at baseline and during 12 months follow-up.

Heart function tests may include the following:

Electrocardiogram (EKG) evaluates the electrical activity of the heart. Electrodes placed on the chest transmit information from the heart to a machine.

Echocardiogram (Echo) is an ultrasound test that uses sound waves to create an image of the heart and examine the function of the heart chambers and valves.

Gated acquisition scan is a nuclear medicine test that uses a small amount of radioactive chemical injected into a vein. A special scanner creates an image of the heart for examining the beating motion of the muscle.

MRI evaluates function of the heart chambers the beating motion of the muscle.

• Study Type: Interventional
• Enrollment (Anticipated): 124
• Phase: Phase 2

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with the first time ST-elevation myocardial infarction (STEMI).
2. Patients after undergoing PCI 2 to 5 days.
3. Patients without PCI but emergency coronary angiography shows the criminal coronary artery recanalized.
4. Left ventricular infarction area seriously hypokinesis or no movement
5. Left ventricular ejection fraction <=45% based on coronary angiography or echocardiography.

Exclusion Criteria:

Any one of the following exclusion criteria is sufficient to disqualify a patient from the study.

1. Patients without emergency PCI and the criminal coronary artery fail to be recanalized.
2. Patients with non-ST-elevation myocardial infarction.
3. Patients with normal left ventricular function.
4. Patients with mechanical complications of myocardial infarction.
5. Patients with a malignant tumor.
6. Patients with infection disease.
7. Less than 6 months since last episode of stroke.
8. Patients with hematological disease (leukemia, myeloproliferative disease, or myelodysplastic syndromes).
9. ALT (GPT) exceeding 100 IU/L.
10. Leukocytes less than 4,000/µL or exceeding 10,000/µL.
11. Platelets less than 100,000/µL.
12. Hemoglobin less than 10 g/dL.
13. Pregnant or nursing patients, those who may be pregnant, or those who plan on becoming pregnant before the end of the study period.
14. Any other reason that the Clinical Supervisors or Clinical Researchers may have for considering a case unsuitable for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Triple

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Phase A: Atorvastatin; Atorvastatin routine dose + placebo transplantation	Drug: Atorvastatin; Routine dose of Atorvastatin therapy; Other Names: Statin
Experimental: Phase A: Low dose BMMSC; Atorvastatin routine dose + low dose BMMSC Transplantation	Drug: Atorvastatin; Routine dose of Atorvastatin therapy; Other Names: Statin; Drug: Low dose BMMSC; Low dose autologous Bone Marrow Mesenchymal Stem Cells transplantation
Experimental: Phase A: Middle dose BMMSC; Atorvastatin routine dose + middle dose BMMSC Transplantation	Drug: Atorvastatin; Routine dose of Atorvastatin therapy; Other Names: Statin; Drug: Middle dose BMMSC; Middle dose autologous Bone Marrow Mesenchymal Stem Cells transplantation
Experimental: Phase A: High dose BMMSC; Atorvastatin routine dose + high dose BMMSC Transplantation	Drug: Atorvastatin; Routine dose of Atorvastatin therapy; Other Names: Statin; Drug: High dose BMMSC; High dose autologous Bone Marrow Mesenchymal Stem Cells transplantation
Placebo Comparator: Phase B: Atorvastatin; Atorvastatin routine dose + placebo transplantation	Drug: Atorvastatin; Routine dose of Atorvastatin therapy; Other Names: Statin
Active Comparator: Phase B: Atorvastatin+Transplantation; Atorvastatin routine dose+ Optimal dose BMMSC Transplantation	Drug: Atorvastatin; Routine dose of Atorvastatin therapy; Other Names: Statin; Drug: Transplantation; Optimal dose autologous Bone Marrow Mesenchymal Stem Cells transplantation
Placebo Comparator: Phase B: Intensive Atorvastatin; Atorvastatin Intensive dose + placebo transplantation	Drug: Intensive Atorvastatin; Intensive dose of Atorvastatin therapy
Experimental: Phase B: Intensive Atorvastatin+Transplantation; Atorvastatin Intensive dose + Optimal dose BMMSC Transplantation	Drug: Transplantation; Optimal dose autologous Bone Marrow Mesenchymal Stem Cells transplantation; Drug: Intensive Atorvastatin; Intensive dose of Atorvastatin therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in left ventricular ejection fraction from baseline to 12 months'	Changes in left ventricular ejection fraction from baseline to 12 months' by MRI	12 months

Collaborators and Investigators

• Sponsor: Yuejin Yang
• Collaborators: Peking Union Medical College Hospital; The First Hospital of Hebei Medical University; Zunyi Medical College

Publications and helpful links

General Publications

• Xu JY, Qian HY, Huang PS, Xu J, Xiong YY, Jiang WY, Xu Y, Leng WX, Li XD, Chen GH, Tang RJ, Huang CR, Hu MJ, Jin C, Wu Y, Zhang J, Qian J, Xu B, Zhao SH, Lu MJ, Shen R, Fang W, Wu WC, Chen X, Wang Y, Li W, Lu XF, Jiang XF, Ma CC, Li JW, Geng YJ, Qiao SB, Gao RL, Yang YJ. Transplantation efficacy of autologous bone marrow mesenchymal stem cells combined with atorvastatin for acute myocardial infarction (TEAM-AMI): rationale and design of a randomized, double-blind, placebo-controlled, multi-center, Phase II TEAM-AMI trial. Regen Med. 2019 Dec;14(12):1077-1087. doi: 10.2217/rme-2019-0024. Epub 2019 Dec 12.

Study record dates

Study Major Dates

• Study Start (Anticipated): March 6, 2018
• Primary Completion (Anticipated): December 31, 2018
• Study Completion (Anticipated): December 31, 2018

Study Registration Dates

• First Submitted: February 7, 2017
• First Submitted That Met QC Criteria: February 7, 2017
• First Posted (Estimate): February 9, 2017

Study Record Updates

• Last Update Posted (Actual): January 25, 2018
• Last Update Submitted That Met QC Criteria: January 23, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: 2016-807-10.1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No