Intravenous MSC Therapy on Ischemia-Reperfusion Injury in Patients With Myocardial Infarction

Nanjing University

Status and phase: Not yet enrolling; Phase 2; Phase 1

Conditions: Myocardial Infarction

Treatments: Drug: CTSTMD PBS without WJ-MSC; Drug: Conventional drug therapy; Biological: WJ-MSC cells implantation

Study type: Interventional

Funder types: Other

Identifiers

NCT03533153

MSC-NanjingUMS

Details and patient eligibility

About

The investigators scheduled to assess the value of intravenous injection of WJ-MSC in patients with ST-segment elevation myocardial infarction (STEMI).

Full description

Ischemia/reperfusion injury in myocardial infarction can induce mass release of oxygen free radicals, trigger inflammatory reaction, and ultimately lead to myocardial remodeling and irreversible cardiac function decline. Microvascular obstruction (MVO) and haemorrhage are common pathological alternations in myocardium post primary PCI, which provide strong prognostic information for STEMI patients. Till now, there is no treatment to be used in clinical practice to reduce myocardium MVO and haemorrhage. With the deep research on stem cells, it is found that the benefits of MSC transplants for myocardium infarction may be achieved by its paracrine effect. Meanwhile, the immunoregulatory effect of MSC has been widely reported in multiply immune disease. Therefore, the applicant proposed the hypothesis that MSC can play an effective role in reducing oxidative stress and inflammatory response, inhibiting microvascular obstruction and haemorrhage. Intravenous injection of MSC will be used in patients with STEMI within 12 hours post primary PCI. The primary endpoint and safety endpoint are recorded in the one year follow up to assess the clinical outcome of intravenous MSC treatment.

Enrollment: 90 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Age between 18 and 75;
2. First performance of anterior acute ST-segment elevation myocardial infarction (STEMI), Killip grade 2 or below on admission;
3. Completing emergency percutaneous coronary intervention within 12h, with TIMI flow grade 0 or 1 (before stent implantation) and 3 (after stent implantation);
4. LVEF in echocardiography is 45% or below primary PCI.

Exclusion criteria

1. Medical history of Q wave myocardial infarction, significant valve disease, pericarditis, pericardial tamponade, myocardiopathy, chronic heart failure or cardio embolism;
2. Non ST-segment elevation myocardial infarction;
3. Chronic occlusion in LCX or RCA besides LAD;
4. Diagnosed with severe coronary artery disease but not yet causing a loss of heart function;
5. Hemodynamic disorders, shock or respiratory failure on admission;
6. Atrial fibrillation with warfarin treatment only or at high risk of bleeding;
7. Constant tachycardia, malignant arrhythmia, complete atrioventricular block, new-onset complete left bundle branch block (LBBB) or pacemaker implantation;
8. Mechanical complications of acute myocardial infarction (interventricular septal defect, rupture of papillary muscle, etc.) or huge left ventricular aneurysm could only be corrected through surgical procedures;
9. Chronic pulmonary heart disease (COPD, bronchial asthma, chronic bronchitis, emphysema or pulmonary heart disease), autoimmune disease or patients on immunosuppressive therapy;
10. Acute infective disease;
11. Hepatitis B/C virus or HIV;
12. Blood system diseases (thrombocytopenia, severe anemia, leukemia, etc.);
13. Severe renal insufficiency, with creatinine clearance (CCr) <33 ml/min or serum creatinine >133 μmol/L;
14. Obvious abnormalities in liver function (ALT and AST 3 times higher than the upper limit of normal value);
15. Medical history of cerebral hemorrhage;
16. Medical history of the malignant tumor;
17. Cognitive impairment, dementia or severe mental illness (SMI);
18. Substantial disability negatively influenced regular follow-up research;
19. Systematic diseases not been effectively controlled or life expectancy < 1 year;
20. Pregnant or lactating women;
21. Not suitable for MRI examination, or could not stick to treatment plans;
22. Could not or not willing to give written informed consent.

Exit Criteria:

1. Intolerable infaust events or changed treatment strategy leading to serious violations of trial conduct;
2. Requiring to exit the clinical trial;
3. Research scheme violations, severely disrupted safety and effectiveness of the trail;
4. Lost to follow-up cases;
5. Conceiving children or want to do that during the treatment period;
6. Candidates not fit to carry on the trial.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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90 participants in 2 patient groups, including a placebo group

WJ-MSC cells implantation group

Experimental group

Description:

MSC cells (allogeneic transplantation from WJ-MSC primary cells); the frequency: for one time within12h after emergency coronary artery revascularization; dose levels: 1X10\^8; method of administration: intravenous injection. Other kinds of treatment are in accordance with the treatment guidelines for MI patients, listed in the column "Conventional drug therapy".

Treatment:

Drug: Conventional drug therapy

Biological: WJ-MSC cells implantation

CTSTMD PBS without WJ-MSC group

Placebo Comparator group

Description:

Saline only was injected in the control group. The frequency: for one time 2-12h after emergency coronary artery revascularization. Dose levels: the same dosage given to MSC group. Method of administration: intravenous injection. Other kinds of treatment are in accordance with the treatment guidelines for MI patients, listed in the column "Conventional drug therapy".

Treatment:

Drug: Conventional drug therapy

Drug: CTSTMD PBS without WJ-MSC