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

Myocardial Infarction Clinical Trial

Official title:

Clinical Study on Ischemia-Reperfusion Injury Using Intravenous Administration of MSC in Patients With Myocardial Infarction Intended to Improve MVO and Prognosis After Surgery

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03533153
• Other study ID #: MSC-NanjingUMS
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: March 1, 2021
• Est. completion date: December 30, 2025

Study information

• Verified date: February 2021
• Source: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Contact: ZILUN WEI, PGT
• Phone: 86-18066045583
• Email: ljdwdth[@]outlook.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 90
• Est. completion date: December 30, 2025
• Est. primary completion date: December 30, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Infarction
• Ischemia
• Myocardial Infarction
• Reperfusion Injury

Intervention

Biological:
• WJ-MSC cells implantation
Laboratory of Stem Cell of Drum Tower Hospital, Nanjing University Medical School, is able to provide types of Good Manufacture Practice (GMP) level stem cells and stem cell-based medicinal products. Clinical-grade WJ-MSC primary cells are cultured to 4~ 8 passages, and the surface markers (CD90+, CD105+, CD45-, CD31-, CD117-) are identified by flow cytometry. WJ-MSC cells are trypsinized and resuspended in the wash buffer of CTSTMD PBS (+Ca2+, +Mg2+). Within 2 hours after enzyme digestion, WJ-MSC cells are shipped to coronary care unit (CCU) and injected into the body.

Drug:
• CTSTMD PBS without WJ-MSC
For Case-control study only.
• Conventional drug therapy
All patients undergo guideline-recommended treatment for STEMI, including aspirin (loading dose of 300mg before maintenance dose of 100 mg/d), clopidogrel (loading dose of 300mg before maintenance dose of 75 mg/d) or Ticagrelor (loading dose of 300mg before maintenance dose of 90 mg/d), angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB), ß-receptor blockers, statins and nitrate esters.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

References & Publications (4)

Ahn JM, Park DW, Lee CW, Chang M, Cavalcante R, Sotomi Y, Onuma Y, Tenekecioglu E, Han M, Lee PH, Kang SJ, Lee SW, Kim YH, Park SW, Serruys PW, Park SJ. Comparison of Stenting Versus Bypass Surgery According to the Completeness of Revascularization in Severe Coronary Artery Disease: Patient-Level Pooled Analysis of the SYNTAX, PRECOMBAT, and BEST Trials. JACC Cardiovasc Interv. 2017 Jul 24;10(14):1415-1424. doi: 10.1016/j.jcin.2017.04.037. — View Citation

Cuculi F, Dall'Armellina E, Manlhiot C, De Caterina AR, Colyer S, Ferreira V, Morovat A, Prendergast BD, Forfar JC, Alp NJ, Choudhury RP, Neubauer S, Channon KM, Banning AP, Kharbanda RK. Early change in invasive measures of microvascular function can predict myocardial recovery following PCI for ST-elevation myocardial infarction. Eur Heart J. 2014 Aug 1;35(29):1971-80. doi: 10.1093/eurheartj/eht434. Epub 2013 Oct 17. — View Citation

Robbers LF, Eerenberg ES, Teunissen PF, Jansen MF, Hollander MR, Horrevoets AJ, Knaapen P, Nijveldt R, Heymans MW, Levi MM, van Rossum AC, Niessen HW, Marcu CB, Beek AM, van Royen N. Magnetic resonance imaging-defined areas of microvascular obstruction after acute myocardial infarction represent microvascular destruction and haemorrhage. Eur Heart J. 2013 Aug;34(30):2346-53. doi: 10.1093/eurheartj/eht100. Epub 2013 Apr 17. — View Citation

Symons R, Pontone G, Schwitter J, Francone M, Iglesias JF, Barison A, Zalewski J, de Luca L, Degrauwe S, Claus P, Guglielmo M, Nessler J, Carbone I, Ferro G, Durak M, Magistrelli P, Lo Presti A, Aquaro GD, Eeckhout E, Roguelov C, Andreini D, Vogt P, Guaricci AI, Mushtaq S, Lorenzoni V, Muller O, Desmet W, Agati L, Janssens S, Bogaert J, Masci PG. Long-Term Incremental Prognostic Value of Cardiovascular Magnetic Resonance After ST-Segment Elevation Myocardial Infarction: A Study of the Collaborative Registry on CMR in STEMI. JACC Cardiovasc Imaging. 2018 Jun;11(6):813-825. doi: 10.1016/j.jcmg.2017.05.023. Epub 2017 Aug 16. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	IS	The primary endpoint is based on patients' myocardial infarction size (IS) as a result of CMR examination. The detection is recorded in the follow up at Month 3.	at Month 3 after treatment.
Secondary	MACCE	Follow up main adverse cardiovascular and cerebrovascular events (MACCE) such as death, myocardial infarction, stroke and heart failure within 1 year after treatment.	within 1 year after PCI.
Secondary	MVO and Hemorrhage	Patients underwent cardiac magnetic resonance imaging (CMR) at Day 4 to Day 7 after presentation with STEMI on a 3.0-T scanner.The change in Microvascular obstruction (MVO) and intramyocardial hemorrhage would be followed up. MVO was defined (and quantified) as hypoenhancement within infarcted myocardium, as determined from LGE images, and was included in the total infarct size. Myocardial oedema was quantified using semi-automatic thresholding, defining AAR as enhancement within myocardium of signal intensity > 2 standard deviations (SDs) above that of a region of interest contoured in remote myocardium. Hypoenhanced areas within the AAR were regarded as intramyocardial haemorrhage (IMH). The MSI was calculated as 100 × [(AAR - infarct size)/AAR]. Infarct size, MVO, AAR and IMH were expressed as %LVM and LV volumes were indexed to body surface area.	at Day 4 to Day 7 after PCI.
Secondary	CMR Markers of Myocardial and Microvascular Damage	CMR markers of myocardial and microvascular damage (myocardial salvage, left ventricular end diastolic volume (LVEDV), left ventricular ejection fraction (LVEF), microvascular obstruction (MVO), intramyocardial hemorrhage) would be followed up at Month 3 after treatment.	at Month 3 after PCI.
Secondary	CK-MB and Troponin	A sensitive troponin T assay for the early diagnosis and risk stratification of myocardial infarction would be evaluated. Blood samples were drawn at baseline and at Hour 6, Hour 12, Hour 24 and Hour 48 after PPCI for cardiac enzyme [creatine kinase MB isoenzyme (CK-MB) and troponin] estimation	at baseline and at Hour 6, Hour 12, Hour 24 and Hour 48 after PCI.
Secondary	Echocardiographic Changes	Changes in echocardiography would be tested at Hour 6, Week 1, Month 1, Month 6 and Year 1 after treatment.	at Hour 6, Week 1, Month 1, Month 6 and Year 1 after PCI.
Secondary	6-min Walk Test	Changes in 6-min walk test would be tested at Hour 6, Week1, Month 1, Month 6 and Year 1 after treatment.	at Hour 6, Week1, Month 1, Month 6 and Year 1 after PCI.
Secondary	Serum BNP	Changes in patients' serum BNP level would be tested at Hour 7, Month 1, Month 6 and Year 1 after treatment.	at Hour 7, Month 1, Month 6 and Year 1 after PCI.
Secondary	MLHFQ Scale	Patients would be required to fill out the quality of life (QQL) scale Minnesota Living with Heart Failure Questionnaire (MLHFQ) at Week1, Month 1, Month 6 and Year 1 after treatment.	at Week1, Month 1, Month 6 and Year 1 after PCI.