Ignite Creation Date:
2024-05-06 @ 12:20 AM
Last Modification Date:
2024-10-26 @ 10:48 AM
Study NCT ID:
NCT01557543
Status:
TERMINATED
Last Update Posted:
2018-07-05
First Post:
2012-03-16
Brief Title:
Stem Cell Injection to Treat Heart Damage During Open Heart Surgery
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Preliminary Assessment of Direct Intra-Myocardial Injection of Autologous Bone Marrow-derived Stromal Cells on Patients Undergoing Revascularization for CAD With Depressed Left Ventricular Function
Status:
TERMINATED
Status Verified Date:
2018-06-18
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background
- Bone marrow stromal stem cells also known as mesenchymal stem cells have been isolated and are found to make large amounts of growth factors Because they make growth factors these cells can help re-grow tissue and encourage repair of damaged tissue Tests on damaged heart muscle suggest that injecting these cells directly into damaged heart muscle can improve heart function Researchers want to give stem cells to people who are having open heart surgery to see if they can help to repair heart muscle damage
Objectives
- To test the safety and effectiveness of bone marrow stromal stem cell injections given during heart surgery to treat heart muscle damage
Eligibility
- Individuals at least 18 years of age who are scheduled to have open heart surgery for heart artery or vein blockages
Design
Participants will be screened with a physical exam and medical history Blood and urine samples will also be collected
Participants will have bone marrow taken from both hip bones about 3 weeks before the heart surgery
During the surgery the stromal stem cells collected from the bone marrow will be given into the damaged portion of the heart muscle The rest of the heart surgery will be performed according to standard procedures
After the surgery participants will be monitored for complications from the stromal stem cells
Participants will have heart function tests to see if the stromal stem cell treatments were effective
- Bone marrow stromal stem cells also known as mesenchymal stem cells have been isolated and are found to make large amounts of growth factors Because they make growth factors these cells can help re-grow tissue and encourage repair of damaged tissue Tests on damaged heart muscle suggest that injecting these cells directly into damaged heart muscle can improve heart function Researchers want to give stem cells to people who are having open heart surgery to see if they can help to repair heart muscle damage
Objectives
- To test the safety and effectiveness of bone marrow stromal stem cell injections given during heart surgery to treat heart muscle damage
Eligibility
- Individuals at least 18 years of age who are scheduled to have open heart surgery for heart artery or vein blockages
Design
Participants will be screened with a physical exam and medical history Blood and urine samples will also be collected
Participants will have bone marrow taken from both hip bones about 3 weeks before the heart surgery
During the surgery the stromal stem cells collected from the bone marrow will be given into the damaged portion of the heart muscle The rest of the heart surgery will be performed according to standard procedures
After the surgery participants will be monitored for complications from the stromal stem cells
Participants will have heart function tests to see if the stromal stem cell treatments were effective
Detailed Description:
Background
Many investigators now believe that bone marrow-derived stem cells or endothelial progenitor cells can be recruited to and incorporated into tissues undergoing neovascularization including cardiac tissue
Stem cells which include hematopoietic stem cells HSCs endothelial progenitor cells EPCs mesenchymal stem cells stromal stem cells MSCs myoblasts and undifferentiated side population cells have been used as an alternative therapeutic strategy for ischemic cardiovascular diseases that cannot be treated by routine interventional approaches
In a porcine pre-clinical study we found that cells survived after intramyocardial injection and differentiated into vascular cells smooth muscle or endothelial cells Functional analysis of regional wall motion and ejection fraction demonstrated statistically significant improvement in function in cell treated animals after six weeks compared with baseline and sham controls
A variety of studies have been conducted in subjects with coronary artery disease using different cell types and routes of administration This study will be the first of its kind to administer autologous BMSC via direct intramyocardial injection in a rigorous clinical trial in the US
Objectives
To evaluate the safety and feasibility of direct intra-myocardial injection of autologous bone marrow stromal cells BMSCs in adult subjects undergoing coronary artery bypass graft CABG or transmyocardial revascularization TMR
A secondary objective is to assess whether direct intra-myocardial injection of autologous bone marrow stromal cells BMSCs improves the patient s cardiac function quality of life and reduces cardiac events compared with historical controls at three and six months after intervention
Eligibility
Adult subjects with three-vessel coronary artery disease who plan to undergo CABG or TMR at the NIH Heart Center at Suburban Hospital and are willing to participate who have stable angina LV EF less than or equal to 50 and who have evidence of hypokinetic segments
Subjects will be excluded if they have had a recent myocardial infarction MI bleeding disorder infection HIV or who are unable to wait 3 weeks for surgery while cells are being expanded prior to injection
Design
Bone marrow aspiration will be performed on subjects who suffer from ischemic heart disease with depressed left ventricular function three weeks before their admission to have CABG or TMR in the NIH Clinical Center Outpatient Clinic
Data will be presented based on the subject s treatment regimen
Group 1 CABGCells total of 10 evaluable subjects
Group 2 TMR Cells total of 10 evaluable subjects
The autologous MSCs will be isolated from the marrow aspirate cultured and expanded in vitro for 3 passages approximately 21 days - 4 days in the Clinical Center Cell Processing Laboratory CPS located in the Department of Transfusion Medicine DTM Clinical Center NIH
During the surgery at Suburban Hospital the MSCs will be injected directly into the ischemic area after CABG or TMR Patients will be assessed for functional improvements pre 3 6 12 and 60 months after the surgery by transthoracic echocardiography andor by MRI at pre 3 and 6 months after surgery Toxicity data will be reported from time of surgery to 6 months after surgery unless later toxicities occur that are related to cell injection
Many investigators now believe that bone marrow-derived stem cells or endothelial progenitor cells can be recruited to and incorporated into tissues undergoing neovascularization including cardiac tissue
Stem cells which include hematopoietic stem cells HSCs endothelial progenitor cells EPCs mesenchymal stem cells stromal stem cells MSCs myoblasts and undifferentiated side population cells have been used as an alternative therapeutic strategy for ischemic cardiovascular diseases that cannot be treated by routine interventional approaches
In a porcine pre-clinical study we found that cells survived after intramyocardial injection and differentiated into vascular cells smooth muscle or endothelial cells Functional analysis of regional wall motion and ejection fraction demonstrated statistically significant improvement in function in cell treated animals after six weeks compared with baseline and sham controls
A variety of studies have been conducted in subjects with coronary artery disease using different cell types and routes of administration This study will be the first of its kind to administer autologous BMSC via direct intramyocardial injection in a rigorous clinical trial in the US
Objectives
To evaluate the safety and feasibility of direct intra-myocardial injection of autologous bone marrow stromal cells BMSCs in adult subjects undergoing coronary artery bypass graft CABG or transmyocardial revascularization TMR
A secondary objective is to assess whether direct intra-myocardial injection of autologous bone marrow stromal cells BMSCs improves the patient s cardiac function quality of life and reduces cardiac events compared with historical controls at three and six months after intervention
Eligibility
Adult subjects with three-vessel coronary artery disease who plan to undergo CABG or TMR at the NIH Heart Center at Suburban Hospital and are willing to participate who have stable angina LV EF less than or equal to 50 and who have evidence of hypokinetic segments
Subjects will be excluded if they have had a recent myocardial infarction MI bleeding disorder infection HIV or who are unable to wait 3 weeks for surgery while cells are being expanded prior to injection
Design
Bone marrow aspiration will be performed on subjects who suffer from ischemic heart disease with depressed left ventricular function three weeks before their admission to have CABG or TMR in the NIH Clinical Center Outpatient Clinic
Data will be presented based on the subject s treatment regimen
Group 1 CABGCells total of 10 evaluable subjects
Group 2 TMR Cells total of 10 evaluable subjects
The autologous MSCs will be isolated from the marrow aspirate cultured and expanded in vitro for 3 passages approximately 21 days - 4 days in the Clinical Center Cell Processing Laboratory CPS located in the Department of Transfusion Medicine DTM Clinical Center NIH
During the surgery at Suburban Hospital the MSCs will be injected directly into the ischemic area after CABG or TMR Patients will be assessed for functional improvements pre 3 6 12 and 60 months after the surgery by transthoracic echocardiography andor by MRI at pre 3 and 6 months after surgery Toxicity data will be reported from time of surgery to 6 months after surgery unless later toxicities occur that are related to cell injection
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 12-H-0078 | None | None | None |