A Study of Allogeneic Mesenchymal Bone Marrow Cells in Subjects With ST Segment Elevation Myocardial Infarction (STEMI)
The purpose of this study is to assess the safety and tolerability of human allogeneic mesenchymal bone marrow cells (aMBMC) administered intravenously to subjects with ST Segment Elevation Myocardial Infarction (STEMI).
ST Segment Elevation Myocardial Infarction (STEMI)
Allogeneic Mesenchymal Bone Marrow Cells
Biological: ALLOGENEIC MESENCHYMAL BONE MARROW CELLS
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A PHASE IIa, DOUBLE-BLINDED, MULTI-CENTER, RANDOMIZED STUDY TO ASSESS THE SAFETY,TOLERABILITY, AND PRELIMINARY EFFICACY OF A SINGLE INTRAVENOUS DOSE OF ALLOGENEIC MESENCHYMAL BONE MARROW CELLS TO SUBJECTS WITH ST SEGMENT ELEVATION MYOCARDIAL INFARCTION (STEMI)|
- The safety and tolerability of aMBMC intravenous administration during the twelve month study period as determined by major adverse events MACE endpoint. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
- The change from baseline on physical exam conducted at day 14 and at 1, 3, 6 and 12 months post-administration, as available: [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- • LV end diastolic volume [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- • LV end systolic volume [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- • Infarct size measured by MRI, with and without contrast (only for patients eligible for MRI) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- • Global Left Ventricular Ejection Fraction (measured by echocardiography) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- • SF-36 Health Assessment [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- • Incidence of Ventricular Arrhythmias requiring intervention at 1 and 3 months post-administration [ Time Frame: 12 months ] [ Designated as safety issue: No ]
|Study Start Date:||February 2013|
|Estimated Study Completion Date:||May 2016|
|Estimated Primary Completion Date:||May 2015 (Final data collection date for primary outcome measure)|
Experimental: High dose group
The high dose group will receive 1.5 million ALLOGENEIC MESENCHYMAL BONE MARROW CELLS per kg body weight
|Biological: ALLOGENEIC MESENCHYMAL BONE MARROW CELLS|
Experimental: Low dose group
The low dose group will receive 1.0 million ALLOGENEIC MESENCHYMAL BONE MARROW CELLS per kg body weight
|Biological: ALLOGENEIC MESENCHYMAL BONE MARROW CELLS|
Placebo Comparator: The Control Group
Control Group will receive placebo consisting of intravenous administration of 1 mL/kg Lactated Ringer's Solution only.
Hide Detailed Description
Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality despite continuing advances in various treatment options. In developed countries, ischemic heart disease causes more than 50% of all cardiovascular deaths. It is estimated that one in three or approximately 80 million American adults have one or more types of CVD, with approximately 38.1 million of those estimated to be 60 years of age or older. The data was extrapolated to the United States population in 2006 from National Health and Nutrition Examination Survey (NHANES) 2005-2006 data.
Mortality data show CVD as the underlying cause of death (including congenital cardiovascular defects) accounting for 35.3% (864,480) of all 2,448,017 deaths in 2005, or one of every 2.8 deaths in the United States. CVD total deaths (1,372,000 deaths in 2005) accounted for about 56% of all deaths in 2005. Nearly 2,400 Americans die of CVD each day, an average of one death every 30 seconds. CVD claims about as many lives each year as cancer, chronic lower respiratory diseases, accidents, and diabetes mellitus combined (NCHS).
Stem cell transplantation has the potential to repair and improve cardiac function, thus helping to significantly decrease morbidity and mortality rates. Preclinical data from a variety of animal studies demonstrated the capacity for skeletal myoblasts to engraft, form myotubules, and enhance cardiac function after transplantation into infarcted myocardium. The underlying sequela of the post infarcted left ventricle often includes massive damage to the cardiomyocyte. The left ventricle remodeling (dilation) and dysfunction is thought to be irreversible. The development of treatments that will regenerate its musculature and vascular components is now considered a main therapeutic challenge. Preliminary human studies focusing on subjects with ischemic heart disease have demonstrated successful myoblast transplantation into the post infarction scar. Another study demonstrated the benefits of stem cell therapy on ventricular function and profusion. Dib et. al., demonstrated the survival, feasibility, and safety of autologous myoblast transplantation and suggests that stem cell transplantation offers a potential therapeutic treatment for end-stage heart disease.
Allogeneic mesenchymal stem cells have been used in a number of clinical trials for different indications. These clinical trials demonstrated the safety of allogeneic mesenchymal stem cell treatment. Allogenic mesenchymal bone marrow cells can be isolated from bone marrow. They are the primary cells used in tissue engineering expressing multiple cell types. Tissue engineering is very promising, generating hope that reconstruction of organs and repair diseased and damaged tissue may be possible.
There are two major types of aMBMC, hematopoetic (mononuclear) and stromal MSCs. Stromal MBMC, the cell type to be used in this study, proved to be more effective in reestablishing profusion as they secreted additional cytokine factors associated with angiogenesis. The multilineage potential of stromal MSCs, their ability to elude detection by the host immune system and even down regulate T-cell response allows for allogeneic multiple stem cell therapeutic use.
Occlusion of the left main or left anterior descending artery causes irreversible injury to the cardiomyocytes in as little as 20 minutes. The goal of therapy in ischemic cardiomyopathy is to limit damage in the following areas:
- Limit infarct size
- Prevent reperfusion injury
- Prevent excessive fibrosis
- Reestablish function of hibernating cardiomyocytes in peripheral zone area.
- Reestablish angiogenesis/vasculogenesis
- Preserve wall motion (prevent arrhythmia and functional contractile deterioration)
- Prevent post infarct ventricular remodeling and left ventricular dilation It is well accepted that dilated cardiomyopathy mortality rates are 50% within 5 years of diagnosis. If we can preserve and restore cardiac function as measured by ejection fraction, preserving left ventricular integrity would increase subject quality of life as well as longevity.
An IV study administering adult allogeneic mesenchymal stem cells (MSC) to 53 subjects following AMI showed excellent safety, reduction in arrhythmias, improvement in functional status and increased ejection fraction. The availability of "off the shelf" allogeneic stem cells will allow for an easily adjustable dose (getting enough cells in the autologous model is often a problem) for each individual subject. The ease of IV administration will make stem cell therapy more cost effective and safer to administer than the current catheter models. This study protocol will expand on the safety and efficacy of aMBMC in subjects suffering from ischemic cardiomyopathy.
|Contact: Ann Campbell, RN||480-728-9973|
|Contact: Kendra Bartels, RN||858-657-5389|
|United States, Arizona|
|Mercy Gilbert and Chandler Medical Center||Recruiting|
|Gilbert, Arizona, United States, 85224|
|Contact: Ann Campbell, RN 480-728-9973|
|Principal Investigator: Nabil Dib, MD, MSc, FACC|
|United States, California|
|University of California, San Diego||Not yet recruiting|
|La Jolla, California, United States, 92037|
|Contact: Kendra Bartels 858-657-5389|
|Principal Investigator: Anthony DeMaria, MD, MACC|