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

February 18, 2021 updated by: Biao Xu, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

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

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed 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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
90

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: WJ-MSC cells implantation group
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".
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.
Other Names:
  • WJ-MSC
Drug: 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), β-receptor blockers, statins and nitrate esters.
Other Names:
  • Conventional
Placebo Comparator: CTSTMD PBS without WJ-MSC group
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".
Drug: 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), β-receptor blockers, statins and nitrate esters.
Other Names:
  • Conventional
Drug: CTSTMD PBS without WJ-MSC
For Case-control study only.
Other Names:
  • CTSTMD PBS

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
IS
Time Frame: at Month 3 after treatment.
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
MACCE
Time Frame: within 1 year after PCI.
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.
MVO and Hemorrhage
Time Frame: at Day 4 to Day 7 after PCI.
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.
CMR Markers of Myocardial and Microvascular Damage
Time Frame: at Month 3 after PCI.
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.
CK-MB and Troponin
Time Frame: at baseline and at Hour 6, Hour 12, Hour 24 and Hour 48 after PCI.
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.
Echocardiographic Changes
Time Frame: at Hour 6, Week 1, Month 1, Month 6 and Year 1 after PCI.
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.
6-min Walk Test
Time Frame: at Hour 6, Week1, Month 1, Month 6 and Year 1 after PCI.
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.
Serum BNP
Time Frame: at Hour 7, Month 1, Month 6 and Year 1 after PCI.
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.
MLHFQ Scale
Time Frame: at Week1, Month 1, Month 6 and Year 1 after PCI.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: BIAO XU, Ph.D., Drum Tower Hospital, Nanjing University Medical School

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2021

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 30, 2023

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 30, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 24, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 9, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 23, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 21, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 18, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MSC-NanjingUMS

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

We have not decided to make it open.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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