Dr. Steven
R.
Bergmann
Beth Israel Medical Center
Cardiology - Baird 5
First Avenue and 16th Street
New York, NY 10003
Phone: 212-420-4681
Fax: 212-420-4222
E-mail: sbergmann@bethisraelny.org
Number of Human Subjects projects reported: 2
| CU-93-62433 | "Detection and Assessment Using Position Emission Tomography of Defects in Myocardial Fatty Acid Utilization Leading to Cardiomyopathy" |
| CU-03-Progenitor Cells | "Noninvasive Imaging of Administered Progenitor Cells " |
"Detection and Assessment Using Position Emission Tomography of Defects in Myocardial Fatty Acid Utilization Leading to Cardiomyopathy"
Principal Investigator: Dr. Steven R. Bergmann, Columbia University
Project started in: 1993
This project ended in fiscal year 2005.
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Identifier or number: AAAA6166
Institutional Review Board (IRB) Review:
Type of Review:
Full Board
Approving Institution: Columbia University
Most recent approval: 05/27/04
IRB approval number: AAAA6166
Explanation of IRB approval:
The IRB was valid through 05/11/2005. Due to th FDA moratorium on production of tracers for human use at Columbia University, the protocol was not renewed. It was also not renewed as we were working on a tracer that would need to go through additional testing before use in humans.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Fiscal Year 2005
Type(s) of Human Subjects Involvement:
A. The objective of this project is to delineate whether defects in myocardial fatty acid metabolism, which can lead to cardiomyopathy and sudden death, can be delineated with positron emission tomography (PET).
B. The research is not, at the current time, used for diagnosis or for decisions regarding treatment to individual subjects, but only for research. Subjects are recruited who have been diagnosed as having cardiomyopathy. Their siblings are also invited to participate. For subjects less than 18 years of age, parental consent is obtained. For subjects greater than 18 years of age, informed written consent is obtained.
C. For assessment of myocardial perfusion, oxygen-15 water is administered intravenously. Regional myocardial perfusion is quantified using a one-compartment mathematical model. For assessment of regional myocardial oxygen consumption, subjects receive carbon-11 acetate intravenously, and for delineation of long-chain fatty acid metabolism, carbon-11 palmitate intravenously. Regional myocardial oxygen consumption and regional myocardial long-chain fatty acid metabolism are delineated with mathematical models. Blood samples are obtained for the analysis of plasma substrates and radioactive metabolites.Tracers made during this study were C-17 heptadecanoic acid and C-15 palmitic acid.
D. Human subjects receive intravenous administration of ionizing radioisotopes. The procedure does involve administration of ionizing radiation. The amount is 29 percent of the maximum permissible to radiation workers in subjects greater than 18 years of age and four percent in subjects less than 18 years of age. This amount of ionizing radiation is too small to have a directly measurable effect. Subjects undergo the research study after an overnight fast (which may be uncomfortable), have an intravenous catheter placed (associated also with discomfort, and potentially bruising, bleeding, or infection), and must lie in the PET scanner for a total of 1-1/2 to 2 hours, in 30 minute intervals (which can be uncomfortable). All data are collected specifically for this project. Subjects are assigned a study number and are not identified by name. Data are maintained in the principal investigator's laboratory under lock and are not disseminated other than to collaborators or to appropriate government agencies.
"Noninvasive Imaging of Administered Progenitor Cells"
Principal Investigator: Dr. Steven R. Bergmann, Columbia University
Project started in: 2003
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Full Board
Approving Institution: Columbia University
Most recent approval: 09/27/05
IRB approval number: AAAB5728
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Fiscal Year 2005
Type(s) of Human Subjects Involvement:
a. Objectives
The objective of this research grant is to develop an approach for labeling progenitor cells, specifically those that we have identified as being able to replace ischemic heart cells, so that the distribution can be followed non-invasively. In addition, the research is aimed at determining whether administration of progenitor cells results in improved myocardial perfusion and function. The efficiency and toxicity of radiolabeling of progenitor cells is also evaluated. We are also evaluating whether improved perfusion can be detected with contrast perfusion echocardiography.
b. Methodology
Briefly, subjects with end-stage ischemic coronary artery disease undergo a screening cardiac positron emission tomography (PET) scan using N-13 ammonia to delineate myocardial perfusion and function. If they qualify based on their PET scan, they undergo an in-hospital protocol where by CD34+ cells are stimulated by the administration of granulocytes-colony stimulating factor (G-CSF). CD34+ cells are then isolated by apharesis, and labeled with indium-111 oxine. Cells are re-infused and subjects undergo single photon emission computed tomography (SPECT) scanning to evaluate uptake and distribution of labeled progenitor cells. Three months after administration of progenitor cells, a cardiac PET scan is repeated to evaluate changes in myocardial perfusion and/or function.
c. Ionizing Radiation
Patients are exposed to nitrogen-13 ammonia and indium-111 oxine labeled progenitor cells.
d. Involvement of Human Subjects
If subjects qualify for this study based on the PET scan and agree to participate, they will be admitted to the Columbia Presbyterian Medical Center on a Monday morning to start the procedure. Subjects will be given subcutaneous injections of G-CSF on Monday, Tuesday, and Wednesday. On Thursday the subject will undergo a procedure called apharesis.
Apharesis is a procedure in which some white blood cells are removed from blood circulation. CD34+ progenitor cells are found in the white blood cell portion of the blood circulation. The procedure involves inserting a needle in each arm by a nurse or physician. The needles are connected to plastic tubing that is connected to the apharesis machine. Once the procedure begins, blood comes from the body through the needle and enters the bowl of the machine where a centrifuge separates the various blood components. The desired amount of white blood cells are collected in a separate bag attached to the apharesis machine and the remainder of plasma, red blood cells, and replacement fluid is returned to the subject. The procedure takes place over a predetermined amount of blood volume determined by weight, height, and blood count. An apharesis treatment lasts from 90 to 120 minutes. Specially trained apharesis personnel perform treatments in the apharesis lab.
CD34+ progenitor cells will be separated out from collected white blood cells. Purified CD34+ progenitor cells will be re-infused to the subject via a needle in the arm following the apharesis course. Six to 24 hours before the cells are given back to the subject, in order to aid in the ability of the CD34+ progenitor cells to go to damaged heart muscle, the subject will have a treadmill exercise test. This test involves walking on the treadmill until the subject cannot walk any more due to chest discomfort, general tiredness, or shortness of breath. During this time changes in the heart will be monitored. The CD34+ progenitor cells will be labeled with a small amount of another radioactive material called indium-111 oxine. The cells are labeled to determine how many of them go to the heart. Approximately 24 and 48 hours after the administration of the cells, the subject will undergo a brief (20 to 30 minute) scan of the heart to determine how many cells went to the heart. Three months after the CD34+ progenitor cell injection, the subject will undergo another adenosine perfusion imaging test using PET and nitrogen-13 ammonia in order to take pictures of the heart and look at heart blood flow and function. The subjects will also have another exercise stress test to see how far they can walk without chest pain. All participants will have blood drawn for standard clinical and experimental reasons prior to the procedures (approximately 3 to 4 tablespoons) and also during their admission to the Research Unit (approximately 20 to 30 tablespoons). Thus, the total amount of blood to be drawn will be approximately 25 to 35 tablespoons for the entire study.
Risks
G-CSF & Apharesis:
The injection of G-CSF into the arm and the drawing of blood samples by inserting a needle into a vein may cause bruising (black and blue marks) and discomfort at the site where the injection/blood is given/taken. There is also the possibility of infection. The injection of G-CSF may be associated with bone pain and, in people with coronary artery disease, chest pain, and perhaps even a heart attack or death. The potential risks of fluid shifts as blood is being removed and re-infused during apharesis may potentially worsen with heart disease. There is a risk of congestive heart failure, unstable angina, heart attack, or death. Study participants may be at greater risk as a result of the severity of their disease state and their general health status. This risk will be evaluated on an individual basis by the doctor and discussed with the subject. An intravenous line will also be required for each drug infusion. Starting the intravenous line may cause a mild degree of discomfort, and there is a small risk of bleeding, infection, or development of a blood clot with any intravenous catheter.
Radiation Exposure
This study involves exposure to radiation from radioactive tracers used to image the heart. The amount of radiation exposure is within accepted limits for studies of this kind and the study will be conducted in compliance with the standard procedures of the institution's Joint Radiation Safety Committee. Although the levels of radiation used in this study are within federal guidelines for research of this type, radiation risks are cumulative over a lifetime, so any additional exposure should be carefully considered.
There may be unforeseeable consequences if the subject is or become pregnant and has participated in this study. These unforeseeable risks may affect the subject as well as the fetus. If the subject is pregnant, lactating, or becomes pregnant during this study, she will be excluded from receiving radioactivity and participating in this study. The possibility also exists that complications and unwanted side effects, which are unknown at this time, could occur.
Confidentiality
Any information that is obtained in connection with this study and that can be identified with the subject will remain confidential and will be disclosed only with his/her permission to people not connected with this study.