Stem Cell Implantation in Patients Undergoing CABG
Primary Purpose
Ischemic Cardiomyopathy, Coronary Artery Disease
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Autologous CD133+ Bone Marrow Stem Cells
Carrier Solution
Sponsored by
About this trial
This is an interventional treatment trial for Ischemic Cardiomyopathy
Eligibility Criteria
Inclusion Criteria:
- 18 years of age or older
- Patients with ischemic heart disease manifested by Canadian class II or greater angina and/or New York Heart Association class II, III or IV exercise intolerance AND who have undergone diagnostic coronary angiography demonstrating at least 70% diameter narrowing of at least 2 major coronary arteries or branches or at least 50% diameter narrowing of the left main coronary artery.
- Left ventricular systolic dysfunction evaluated by echocardiography or LV angiography (LV ejection fraction less than or equal to 49%).
- No contraindications or exclusions (see below)
- Willingness to participate and ability to provide informed consent
Exclusion Criteria:
- Contraindications to magnetic resonance imaging .
- Need for emergent revascularization.
- Need for concomitant surgical procedure at the time of CABG (e.g. valve repair or replacement, aneurysm resection, etc.).
- Hemodynamically unstable patients.
- Patients with confirmed transmural myocardial infarction within 4 weeks, and/or rising cardiac biomarker proteins (i.e. troponin), and/or worsening ECG changes.
- Prior CABG surgery.
- Stroke within 1 month prior to planned CABG.
- Diagnosed with human immunodeficiency virus (HIV) or any other immune disorder or immunosuppressive medication (e.g. prednisone, cyclophosphamide, etanercept, etc.)
- Organ dysfunction
- Contra-indication for bone marrow aspiration (Thrombocytopenia < 50.000 mm3, INR > 2.0, use of antiplatelet agents other than aspirin).
- Hemoglobin less than 8g/dL, white blood cell count less than 4,000/mm3, absolute neutrophil count less than 1500/mm3
- Active infection
- Myelodysplastic syndrome (MDS)
- Significant cognitive impairment
- Any condition associated with a life expectancy of less than 6 months
- Patients known allergic reaction or contraindication to any of the component of the CD133+ enriched cells
- Participation in other studies concomitant with this study
- History of severe ventricular tachy-arrythmias
- Inability or unwillingness to provide written informed consent
- Positive serum pregnancy test
Sites / Locations
- University of Pennsylvania
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Autologous CD133+ Bone Marrow Stem Cells
Carrier Solution
Arm Description
Intra-myocardial injection of autologous CD133+ cells in suspension.
Intra-myocardial inception of carrier solution.
Outcomes
Primary Outcome Measures
Freedom from a Major Adverse Cardiac Event (MACE)
Defined as cardiac death, myocardial infarction (CK/CK-MB over 5 times the upper limit of normal), repeat coronary bypass grafting, or a repeat percutaneous intervention of bypassed coronary artery.
Feedom from any major arrhythmias
Defined as sustained ventricular tachycardia or survived sudden death.
Secondary Outcome Measures
Regional myocardial perfusion and function assessed by comparing paired magnetic resonance scans, ECHOs and SPECT scans obtained prior to CABG and again at 6 months post CABG.
Symptom severity and quality of life at 6 months after CABG surgery.
Full Information
NCT ID
NCT01721902
First Posted
October 1, 2012
Last Updated
December 3, 2013
Sponsor
Miltenyi Biotec, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01721902
Brief Title
Stem Cell Implantation in Patients Undergoing CABG
Official Title
Stem Cell Implantation in Patients Undergoing CABG
Study Type
Interventional
2. Study Status
Record Verification Date
December 2013
Overall Recruitment Status
Terminated
Why Stopped
The study was terminiated due the lack of recruitment.
Study Start Date
January 2010 (undefined)
Primary Completion Date
October 2013 (Actual)
Study Completion Date
December 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Miltenyi Biotec, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary objective of this study is to demonstrate the feasibility and safety of intra-operative, intra-myocardial injection of autologous CD133 positive bone marrow cells at the time of coronary artery bypass graft (CABG) surgery in patients with chronic ischemic cardiomyopathy. Additionally, the feasibility of producing autologous CD133+ bone marrow stem cells will be assessed.
The investigators hypothesize that collection of a sufficient number of CD133+ cells through bone marrow aspiration prior to surgery, with subsequent processing and intra-myocardial injection of high purity cells following completion of CABG, will be feasible without significant adverse clinical consequences.
Detailed Description
Coronary heart disease (CHD) is the leading cause of death in the U.S. in both men and women and the aging of the population and rising prevalence of diabetes ensure that the number of persons with CHD will continue to increase over the next several decades. Two major factors contributing to adverse outcomes in patients undergoing coronary artery bypass grafting (CABG) surgery are failure to achieve complete revascularization, and residual impairment in left ventricular function.
In the present study, the investigators propose a Phase I randomized double-blind study designed to assess the feasibility and safety of autologous CD133+ cells in patients referred for CABG who have significant regions of viable but non-revascularizable myocardium and/or significant LV systolic dysfunction not likely to improve with conventional coronary revascularization.
Autologous CD133+ bone marrow progenitor cells will be harvested from study subjects at the time of CABG, processed and then injected into patients' myocardium prior to completion of CABG surgery. The test material consists of autologous CD133+ cells. Since intra-myocardial injections per se could stimulate neovascularization, control group patients will receive a placebo injection of carrier solution. Control subjects will thus have an identical procedure to those randomized to autologous CD133+ cell injections.
The three goals of the study are as follows:
To demonstrate the feasibility and safety of intra-operative, intra-myocardial injection of autologous CD133+ bone marrow cells in adults with chronic ischemic cardiomyopathy associated with impair left ventricular function.
To assess the effect of autologous CD133+ cell injections on regional myocardial perfusion and function by comparing paired magnet resonance scans obtained prior to CABG and again 6 months post CABG.
To assess the effect of autologous CD133+ stem cell injections on symptom severity and quality of life at 6 months after CABG surgery.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ischemic Cardiomyopathy, Coronary Artery Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
23 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Autologous CD133+ Bone Marrow Stem Cells
Arm Type
Active Comparator
Arm Description
Intra-myocardial injection of autologous CD133+ cells in suspension.
Arm Title
Carrier Solution
Arm Type
Placebo Comparator
Arm Description
Intra-myocardial inception of carrier solution.
Intervention Type
Device
Intervention Name(s)
Autologous CD133+ Bone Marrow Stem Cells
Intervention Description
Intra-myocardial injection of 2-3 x 10E6 CD133+ Bone Marrow Stem Cells
Intervention Type
Other
Intervention Name(s)
Carrier Solution
Intervention Description
Intra-myocardial injection of carrier solution
Primary Outcome Measure Information:
Title
Freedom from a Major Adverse Cardiac Event (MACE)
Description
Defined as cardiac death, myocardial infarction (CK/CK-MB over 5 times the upper limit of normal), repeat coronary bypass grafting, or a repeat percutaneous intervention of bypassed coronary artery.
Time Frame
Six months
Title
Feedom from any major arrhythmias
Description
Defined as sustained ventricular tachycardia or survived sudden death.
Time Frame
Six months
Secondary Outcome Measure Information:
Title
Regional myocardial perfusion and function assessed by comparing paired magnetic resonance scans, ECHOs and SPECT scans obtained prior to CABG and again at 6 months post CABG.
Time Frame
6 months
Title
Symptom severity and quality of life at 6 months after CABG surgery.
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
18 years of age or older
Patients with ischemic heart disease manifested by Canadian class II or greater angina and/or New York Heart Association class II, III or IV exercise intolerance AND who have undergone diagnostic coronary angiography demonstrating at least 70% diameter narrowing of at least 2 major coronary arteries or branches or at least 50% diameter narrowing of the left main coronary artery.
Left ventricular systolic dysfunction evaluated by echocardiography or LV angiography (LV ejection fraction less than or equal to 49%).
No contraindications or exclusions (see below)
Willingness to participate and ability to provide informed consent
Exclusion Criteria:
Contraindications to magnetic resonance imaging .
Need for emergent revascularization.
Need for concomitant surgical procedure at the time of CABG (e.g. valve repair or replacement, aneurysm resection, etc.).
Hemodynamically unstable patients.
Patients with confirmed transmural myocardial infarction within 4 weeks, and/or rising cardiac biomarker proteins (i.e. troponin), and/or worsening ECG changes.
Prior CABG surgery.
Stroke within 1 month prior to planned CABG.
Diagnosed with human immunodeficiency virus (HIV) or any other immune disorder or immunosuppressive medication (e.g. prednisone, cyclophosphamide, etanercept, etc.)
Organ dysfunction
Contra-indication for bone marrow aspiration (Thrombocytopenia < 50.000 mm3, INR > 2.0, use of antiplatelet agents other than aspirin).
Hemoglobin less than 8g/dL, white blood cell count less than 4,000/mm3, absolute neutrophil count less than 1500/mm3
Active infection
Myelodysplastic syndrome (MDS)
Significant cognitive impairment
Any condition associated with a life expectancy of less than 6 months
Patients known allergic reaction or contraindication to any of the component of the CD133+ enriched cells
Participation in other studies concomitant with this study
History of severe ventricular tachy-arrythmias
Inability or unwillingness to provide written informed consent
Positive serum pregnancy test
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yi-Ping J Woo, M.D.
Organizational Affiliation
University of Pennsylvania
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
12. IPD Sharing Statement
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Stem Cell Implantation in Patients Undergoing CABG
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