WJMSCs Anti-inflammatory Therapy in Acute Myocardial Infarction (WAIAMI)
Primary Purpose
Acute Myocardial Infarction
Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Intravenous infusion placebo
Intravenous infusion WJMSCs
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myocardial Infarction focused on measuring AMI;, Mesenchymal Stem Cells;, anti-inflammatory;
Eligibility Criteria
Inclusion Criteria:
- Age limited ≥ 18 years at Visit 1
- Patient must provide written informed consent
- Have a diagnosis of acute ST-Segment-Elevation or Non-ST-Segment-Elevation myocardial infarction as defined by any of the following criteria:
- According to the Third Universal Definition of Myocardial Infarction Type:
Type 1 spontaneous myocardial infarction Type 2 myocardial infarction secondary to an ischemic imbalance Type 3 myocardial infarction resulting in death when biomarker values are unavailable Including: acute ST-Segment-Elevation or Non-ST-Segment-Elevation myocardial infarction, creatine kinase (CK)-MB levels over three-fold the upper limit of the reference values.
- Successful or unsuccessful. revascularization by percutaneous coronary intervention, within 12 hours after symptom onset with stent implantation and thrombolysis.
Exclusion Criteria:
- Myocardial infarction related to stent thrombosis; Myocardial infarction related to restenosis
- Myocardial infarction related to coronary artery bypass grafting (CABG)
- Have a hematologic abnormality as evidenced by hematocrit <25% , white blood cell <2500/u L or platelet values<100000/u L without another explanation.
- Have liver dysfunction , as evidenced by enzymes (aspartate aminotransferase and alanine aminotransferase) >3× the upper limits of normal
- Have a coagulopathy (international normalized ratio > 1.3) not because of a reversible cause (ie, coumadin)
- Be an organ transplant recipient
- Have a clinical history of malignancy within 5 y except curatively treated basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma.
- Have a noncardiac condition that limits lifespan to <1y.
- Have a history of drug or alcohol abuse within the past 24 m.
- Be serum positive for human immunodeficiency virus, hepatitis B surface antigen, or hepatitis C.
- Be a female who is pregnant, nursing, or of childbearing potential who is not practicing effective contraceptive methods.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Active Comparator
Arm Label
Placebo PBS
WJMScs
Arm Description
Standard therapy+Intravenous infusion PBS in patients with AMI
Standard therapy+Intravenous infusion WJMSCs in patients with AMI
Outcomes
Primary Outcome Measures
Any composite of major adverse cardiovascular events
The main safety endpoints was the first occurrence of a major adverse cardiovascular event (a composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) and hospitalization for unstable angina that led to urgent coronary revascularization within 12 months.
Checking patient LVEF
The main feasibility endpoints were defined as the change in LVEF, infarct size as determined by MRI and perfusion defect as assessed by MIBI SPECT from baseline to 6 months.
Checking patient infarct size
The main feasibility endpoints were defined as the change in infarct size
checking patient perfusion defect.
The main feasibility endpoints were defined as non significant perfusion defect
Secondary Outcome Measures
Coronary disease
Secondary end points included death from a composite of major adverse card cardiovascular events plus any coronary revascularization within 12 months.
Coronary congestive heart failure
Secondary end points included death from hospitalization for congestive heart failure within 12 months.
Coronary changes in hsCRP
Secondary end points included the level change of hsCRP within 12 months.
Full Information
NCT ID
NCT04551443
First Posted
December 12, 2019
Last Updated
September 10, 2020
Sponsor
Navy General Hospital, Beijing
Collaborators
Peking University Third Hospital, Peking Union Medical College Hospital, Xijing Hospital, Chinese PLA General Hospital
1. Study Identification
Unique Protocol Identification Number
NCT04551443
Brief Title
WJMSCs Anti-inflammatory Therapy in Acute Myocardial Infarction
Acronym
WAIAMI
Official Title
Randomised, Double-blind, Placebo-controlled, Intravenous Infusion Human Wharton' Jelly-derived Mesenchymal Stem Cells in Patients With Acute Myocardial Infarction
Study Type
Interventional
2. Study Status
Record Verification Date
December 2019
Overall Recruitment Status
Unknown status
Study Start Date
November 1, 2020 (Anticipated)
Primary Completion Date
December 30, 2021 (Anticipated)
Study Completion Date
December 30, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Navy General Hospital, Beijing
Collaborators
Peking University Third Hospital, Peking Union Medical College Hospital, Xijing Hospital, Chinese PLA General Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Cumulative evidence has demonstrated that cardiac repair after acute myocardial infarction (AMI) is characterized by a series of time-dependent events orchestrated by the innate immune system. This begins immediately after the onset of necrotic cell death with intense sterile inflammation and myocardial infiltration of a variety of immune cell subtypes including monocytes and macrophages during the first several days after MI. There is increasing evidence to suggest inflammation is not limited to the infarcted myocardium and systemic imbalances in the post-infarct inflammatory cascade can exacerbate adverse remodelling beyond the infarct site. Therefore, it is very important that therapies seek to target the intricate balance between pro- and antiinflammatory pathways timely after AMI. Human mesenchymal stem cells (hMSCs) have been shown to exhibit immunomodulation, angiogenesis, and paracrine secretion of bioactive factors that can attenuate inflammation and promote tissue regeneration, making them a promising cell source for AMI therapy. However, it has been proved in our and other studies that perfusion of WJMSCs after 5 days of AMI can only slightly improve left ventricular end-diastolic volume, which is the most important indicator of left ventricular remodeling. Thus, WANIAMI Trial is a randomized, double-blind, placebo controlled, phase#study designed to assess the safety and feasibility of intravenous infusion of WJMSCs in the treatment of patients in the acute phase ( within 24h) with the both of ST-Segment-Elevation or Non-ST-Segment-Elevation AMI.
Detailed Description
At present, although the implementation of timely reperfusion strategies has reduced the acute mortality associated with AMI, improved patient survival has increased the incidence of chronic heart failure, due in large part to adverse remodeling of the damaged left ventricle (LV) following the initial ischemic event. However, recently, pathophysiological mechanisms of AMI reveal that begins immediately after the onset of necrotic cell death with intense sterile inflammation and myocardial infiltration of a variety of immune cell subtypes including neutrophils, monocytes and macrophages during the first several days after MI. Improved understanding in the interactions between cells, extracellular matrix (ECM) and signaling molecules within the injured myocardium have allowed development of novel experimental therapies. These therapies seek to target the intricate balance between pro- and anti-inflammatory pathways in an attempt to limit ischemic injury and prevent subsequent development of heart failure. Mesenchymal stem cells (MSCs), in particular, have emerged as potent paracrine modulators of inflammation that promote myocardial healing after infarction.
The latest cell biological studies have demonstrated that mesenchymal stem cells have a unique immunomodulatory function. MSCs contribute to a critical role in regulating the inflammatory microenvironment and interacting with immune cells, including T cells, B cells, natural killer (NK) cells, and dendritic cells (DCs). MSC induce anti- inflammatory macrophages, inhibit foam cell formation, suppress immune responses of endothelial cells and innate lymphoid cells, and increase phagocytic capacity, which indirectly suppresses T cell proliferation. In mouse AMI models, we found MSCs transplantation significantly reduced the number of inflammatory macrophages (M1), increased the number of anti-inflammatory macrophages (M2) and prevented the expansion of AMI during early stage of AMI. More recently, the paracrine potency might vary with sources and microenvironment of MSCs. MSCs isolated from fetal tissues such as umbilical cord (UC) and UC-blood (UCB) were shown to have increased secretion of anti-inflammatory factors (TGF-β,IL-10) and growth factors than MSCs obtained from adult adipose tissue or bone marrow. Our previous research found that the expression characteristics of special immunomodulatory genes of human umbilical cord Wharton's jelly-derived MSCs (WJMSCs). At present, many studies have demonstrated WJMSC possess s a robust immunomodulatory potential and anti-inflammatory effects through release of secretome consisting of a diverse range of cytokines, chemokines, and extracellular vesicles (EVs), the cross talk and interplay of WJMSCs and local environment reversely control and regulate the paracrine activity of MSCs. Thus WJMSCs are important regulators of immune responses and may hold great potential to be used as a therapeutic in AMI. In particular#safety and feasibility of WJMSCs transplant have been clearly proved by us and other studies in patients with AMI.
Given the current evidence, systemic paracrinemediated anti-inflammatory effects of WJMSCs can drive beneficial in therapy of AMI. These concepts lead to a potentially transformative strategy that intravenous delivery of WJMSCs, through systemic anti-infammatory mechanisms.
Therefore, the investigators performed a double-blind, placebo- controlled trial, randomly assigning 200 patients with AMI to receive three times at 30-day intervals for equal doses of 1x106 /kg of WJMSCs, first time infusing within 24h after AMI or placebo , to investigate the therapeutic efficacy and safety of WJMSCs in patients with acute ST-Segment-Elevation or Non-ST-Segment-elevation myocardial infarction.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myocardial Infarction
Keywords
AMI;, Mesenchymal Stem Cells;, anti-inflammatory;
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Placebo Comparator: Intravenous infusion WJMSCs +standard therapy Vs placebo+ standard therapy in patients with acute myocardial infarction
Masking
ParticipantInvestigator
Masking Description
The eligible patients were assigned randomly to each of two groups (WJMSCs or placebo control) in a 1:1 fashion using a computer-generated randomization of sequence numbers. Physicians and other clinical personnel remained blind to the treatment assignment throughout the study.
Allocation
Randomized
Enrollment
200 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Placebo PBS
Arm Type
Placebo Comparator
Arm Description
Standard therapy+Intravenous infusion PBS in patients with AMI
Arm Title
WJMScs
Arm Type
Active Comparator
Arm Description
Standard therapy+Intravenous infusion WJMSCs in patients with AMI
Intervention Type
Biological
Intervention Name(s)
Intravenous infusion placebo
Other Intervention Name(s)
PBS
Intervention Description
Intravenous infusion placebo or WJMSCs in patients with AMI
Intervention Type
Biological
Intervention Name(s)
Intravenous infusion WJMSCs
Other Intervention Name(s)
WJMSCs
Intervention Description
Intravenous infusion WJMSCs or placebo in patients with AMI
Primary Outcome Measure Information:
Title
Any composite of major adverse cardiovascular events
Description
The main safety endpoints was the first occurrence of a major adverse cardiovascular event (a composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) and hospitalization for unstable angina that led to urgent coronary revascularization within 12 months.
Time Frame
12 months
Title
Checking patient LVEF
Description
The main feasibility endpoints were defined as the change in LVEF, infarct size as determined by MRI and perfusion defect as assessed by MIBI SPECT from baseline to 6 months.
Time Frame
6 months
Title
Checking patient infarct size
Description
The main feasibility endpoints were defined as the change in infarct size
Time Frame
6 months
Title
checking patient perfusion defect.
Description
The main feasibility endpoints were defined as non significant perfusion defect
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Coronary disease
Description
Secondary end points included death from a composite of major adverse card cardiovascular events plus any coronary revascularization within 12 months.
Time Frame
12 months
Title
Coronary congestive heart failure
Description
Secondary end points included death from hospitalization for congestive heart failure within 12 months.
Time Frame
12 months
Title
Coronary changes in hsCRP
Description
Secondary end points included the level change of hsCRP within 12 months.
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age limited ≥ 18 years at Visit 1
Patient must provide written informed consent
Have a diagnosis of acute ST-Segment-Elevation or Non-ST-Segment-Elevation myocardial infarction as defined by any of the following criteria:
According to the Third Universal Definition of Myocardial Infarction Type:
Type 1 spontaneous myocardial infarction Type 2 myocardial infarction secondary to an ischemic imbalance Type 3 myocardial infarction resulting in death when biomarker values are unavailable Including: acute ST-Segment-Elevation or Non-ST-Segment-Elevation myocardial infarction, creatine kinase (CK)-MB levels over three-fold the upper limit of the reference values.
Successful or unsuccessful. revascularization by percutaneous coronary intervention, within 12 hours after symptom onset with stent implantation and thrombolysis.
Exclusion Criteria:
Myocardial infarction related to stent thrombosis; Myocardial infarction related to restenosis
Myocardial infarction related to coronary artery bypass grafting (CABG)
Have a hematologic abnormality as evidenced by hematocrit <25% , white blood cell <2500/u L or platelet values<100000/u L without another explanation.
Have liver dysfunction , as evidenced by enzymes (aspartate aminotransferase and alanine aminotransferase) >3× the upper limits of normal
Have a coagulopathy (international normalized ratio > 1.3) not because of a reversible cause (ie, coumadin)
Be an organ transplant recipient
Have a clinical history of malignancy within 5 y except curatively treated basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma.
Have a noncardiac condition that limits lifespan to <1y.
Have a history of drug or alcohol abuse within the past 24 m.
Be serum positive for human immunodeficiency virus, hepatitis B surface antigen, or hepatitis C.
Be a female who is pregnant, nursing, or of childbearing potential who is not practicing effective contraceptive methods.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ning K Zhang, MS
Phone
13011864761
Email
zhangningkun2004@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Chen Yu, MD.PhD
Phone
18600310120
Email
yuchen911@hotmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lian Ru Gao, MD
Organizational Affiliation
The Sixth Medical Center of P.L.A. General Hospital
Official's Role
Study Chair
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
WJMSCs Anti-inflammatory Therapy in Acute Myocardial Infarction
We'll reach out to this number within 24 hrs