USDOE Human Subjects Research Database, Fiscal Year 2003

Columbia University

Public Information Contact:

Dr. Steven R. Bergmann
Beth Israel Medical Center
Cardiology - Baird 5
First Ave and 16th St
New York, NY 10003

Phone: 212-420-4681
Fax: 212-420-4222
E-mail: sbergman@chpnet.org

Institutional Review Board (IRB):

Human Subject Projects:

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 "

Project Identifier: CU-93-62433

"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

Project Funding Information:

Funding for Human Subjects Research:

DOE: Office of Biological and Environmental Research (OBER)

$310,000.00 (Est.) for: Fiscal Year 2003

Information on Use of Human Subjects:

This project involves the use of multiple protocols/subprojects.
Number of protocols/subprojects associated with this project: 1

Identifier or number: 7874

Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Columbia University
Most recent approval: 12/06/02
IRB approval number: 7874

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 2003

Type(s) of Human Subjects Involvement:

Internal administration of radioactive substances to human subjects:

• For clinical research

Internal use of chemical substances (solid, liquid, or gas) on human subjects:

• For clinical research

Collection of personally identifiable bodily materials (blood or blood products, urine, cells, tissue, teeth, organs, excreta, etc):

• Using bodily materials collected specifically for this project.

(a. Objectives, b. Methodology, c. Ionizing Radiation, Radioactive Substances, or Chemical Substances to which human subjects are exposed, d. Involvement of Human Subjects [d.1. procedures used, d.2. risks if any])

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. 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, and for delineation of vascular structures (in subjects greater than 18 years of age), oxygen-15 carbon monoxide is administered by inhalation. 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.

D. Human subjects receive intravenous administration of ionizing radioisotopes, and subjects greater than 18 years of age also receive the ionizing radioisotopes by inhalation. 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.

Project Identifier: CU-03-Progenitor cells

"Noninvasive Imaging of Administered Progenitor Cells"

Principal Investigator: Dr. Steven R. Bergmann, Columbia University

Project started in: 2003

Project Funding Information:

Funding for Human Subjects Research:

DOE: Office of Biological and Environmental Research (OBER)

$101,440.00 (Est.) for: Fiscal Year 2003

Information on Use of Human Subjects:

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: 01/17/03
IRB approval number: 14577

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 2003

Type(s) of Human Subjects Involvement:

Internal administration of radioactive substances to human subjects:

• For clinical research

Internal use of chemical substances (solid, liquid, or gas) on human subjects:

• For clinical research

Collection of personally identifiable bodily materials (blood or blood products, urine, cells, tissue, teeth, organs, excreta, etc):

• Using bodily materials collected specifically for this project.

Use of personally identifiable data from questionnaires, surveys, or epidemiological studies:

• Using data collected from subjects specifically for this project.

(a. Objectives, b. Methodology, c. Ionizing Radiation, Radioactive Substances, or Chemical Substances to which human subjects are exposed, d. Involvement of Human Subjects [d.1. procedures used, d.2. risks if any])

Progenitor cell therapy holds the potential for the treatment of numerous disease states. Our group has shown that CD34+ progenitor cells can home into ischemic myocardium and induce new vascular growth as well as induce cardiomyocyte formation.

The aim of the proposed research is to evaluate whether indium-111 oxine can be used to label progenitor cells, evaluate the toxicity of labeling and biodistribution of labeled progenitor cells, and evaluate their use in both experimental and human studies.

After initial in-vitro toxicity and in-vivo biodistribution studies are completed, we will evaluate the ability of CD34+ cells to track into ischemic myocardium in a rat model of coronary ligation. Subsequently, we will evaluate the ability of labeled cells to be imaged in human subjects with intractable coronary artery disease after stimulation of the bone marrow with GCSF, CD34+ cell selection, labeling, and reinfusion. Positron emission tomomgraphy (PET) scans will be used prior to, and 3 months after cell labeling and reinfusion to determine changes in myocardial blood flow.