Dr. David Eisenberg
Box 951570
Los Angeles, CA 90095-1570
Phone: 310-825-3754
Fax: 310-206-3914
Email: david@uclaue.mbi.ucla.edu
Projects are approved by an IRB located at: University of California, Los Angeles.
The approving IRB operates under a Multiple Project Assurance (MPA) recognized by DOE or by the Department of Health and Human Services (HHS).
MPA number of the IRB: M-1127
Number of Human Subjects Projects reported: 1
Project Identifier: UCLA-47-87ER60615
Project Title:
Structural Biology and Molecular Medicine Research Program/Nuclear Medicine Applications (see projects numbered UCLA-89-12-515-4 in 1994 database)
Principle Investigator:
Dr. David Eisenberg
Principle Investigator's Institution: University of California, Los Angeles
Project started in: 1947
Project Funding Information:
Project received funding in Fiscal Year 1995.
Project used human subjects in Fiscal Year 1995.
Funding Sources:
Direct costs of research project
Project involves use of multiple protocols/subprojects.
Number of protocols/subprojects associated with this project: 11
Protocol/Subproject # 1
Protocol/Subproject Identifier: 91-12-542
IRB Review:
Type of Review: Expedited
Most Recent Approval: December 19, 1994
Number of Human Subjects in the Last Reporting Period for this Project: 0
(Reporting periods vary.)
Type of Human Subjects Involvement:
TITLE: "Pathogenesis of symptomatic versus silent myocardial ischemia". The PI on this project is Heinrich R. Schelbert, M.D. No studies were performed during FY95.
Patients, male or female, ages 21-75, from outpatient cardiology clinics at Wadsworth Veterans Administration Medical Center (VAMC) and UCLA Medical Center, with stable coronary artery disease/angina, will be recruited to study the pathophysiological differences between silent myocardial ischemic episodes and symptomatic ischemic episodes. It has been established that frequent episodes of silent myocardial ischemia exist in all subsets of patients with symptomatic ischemia (otherwise known as angina pectoris) and represent 70% to 90% of all ischemic episodes. Why myocardial ischemia remains silent in a person who also has symptomatic episodes remains unknown. Possible causes include differences in pain thresholds, defective warning signals, b-endorphin activity, duration of ischemic episodes, myocardial hemodynamic demand and extent/severity of ischemia.
Positron emission tomography (PET), with its unique ability to quantitate metabolically impaired (ischemic) tissue, will be used for this study. About 20 patients per year will be studied.
Baseline clinical data will be obtained, including Holter monitoring to verify preset criteria for the presence of symptomatic and silent ischemic episodes. Baseline PET studies include blood flow using the radionuclides N-13 ammonia or Rb-82 and metabolic imaging using F-18 fluorodeoxyglucose. Hemodynamic variables and catecholamine levels will be measured.
Mental stress tests will be done to provoke silent ischemia, and PET scans for blood flow and metabolic imaging will be performed during an ischemic episode, signaled by specialized Holters with on-line analysis. Two days later, the above scan procedure will be repeated during symptomatic ischemia provoked by supine bicycle exercise.
The tracer amounts of radioactivity used are well within the guidelines for permissible exposure. Additional potential risks include blood sampling.
IRB Review:
Type of Review: Expedited
Most Recent Approval: February 07, 1995
Number of Human Subjects in the Last Reporting Period for this Project: 0
(Reporting periods vary.)
Type of Human Subjects Involvement:
TITLE: "Metabolic tissue characterization in patients with acute myocardial infarction by positron emission tomography". The PI on this project is Heinrich R. Schelbert, M.D. No studies were performed in FY95.
The benefit of the study is primarily directed toward medical science. The study is expected to provide information on the metabolic pattern of infarcted and ischemically injured myocardium in humans. An early differentiation between viable and necrotic tissue during an evolving infarct will then allow better definition of patients who will benefit from therapuetic interventions such as angioplasty or surgical revascularization. For the individual patient, there will be the benefit of assessing the severity and extent of disease which may be important information for further management.
For the study early after the acute infarction, the patient will be transported from the UCLA Coronary Care Unit (CCU) to the UCLA Nuclear Medicine Clinic where the positron tomograph is located. He/she will be escorted by a CCU nurse and cardiologist or cardiologist fellow. The follow-up study will be performed electively on an outpatient basis approximately 6 weeks later. For the study later after an acute myocardial infarction, patients will be examined first at the time of hospital discharge, 10-14 days post myocardial infarction and then again at 3 months. Concurrent with the PET studies will be gated MRI evaluation of the heart in terms of tissue characterization and regional function. This protocol seeks to examine the predictive value of residual metabolic abnormality as seen on PET for subsequent characterization. The study will be performed jointly with the cardiology group at Cedars Sinai Medical Center, where the gated MRI studies will be obtained. Both scintigraphic studies include the injection of 82Rubidium, 18Fluorodeoxyglucose and 11Carbon palmitate.
During the 1st study, the patient will be continuously monitored electrocardiographically, and hemodynamical monitoring will be performed periodically. The cardiologist will be present throughout the stay of the patient in the Nuclear Medicine Clinic. The scanner room is equipped with all standard cardiac monitoring and emergency devices including defibrillator. The additional risk to the patient by participating in the study is considered minimal, since no intervention is involved which significantly stresses the cardiovascular system. However, sudden arrhythmias can occur in patients with acute infarct. Therefore, care will be taken to continuously monitor the patient.
Patients' diagnoses of acute myocardial infarction must be established by ECG and enzyme criteria. Hemodynamically and clinically unstable patients will be excluded. Patients with life threatening dysrhythmias will not be considered. Additionally, patients who are deemed unable to comprehend the context of the study either due to the disease or drug intervention will be excluded. The selection will be discussed with the referring physician of the patient and the attending staff of the CCU.
IRB Review:
Type of Review: Expedited
Most Recent Approval: April 17, 1995
Number of Human Subjects in the Last Reporting Period for this Project: 0
(Reporting periods vary.)
Type of Human Subjects Involvement:
TITLE: "Mapping dopamine receptors with F-18 fluorospiperone". The PI on this project is Lewis R. Baxter, M.D.
This protocol uses a trace amount of a compound which binds specifically to key sites in the brain that have been implicated in a variety of disease processes involving mental illness and neurological disorders. Some of the illnesses that affect these receptor sites include depression, schizophrenia, movement disorders and behavioral abnormalities following head trauma. To measure these receptors, we administer a trace amount of a radioactive compound into the subject's vein while sampling blood from a vein or artery. While this is happening, the subject is lying on a couch with his or her head in a large machine (tomograph) that records the radioactivity from the compound as it passes through the brain. These serial pictures plus the information about the behavior of the compound in the blood allow for the precise and accurate measurement of these receptors in the brain. Once known in normal subjects, changes associated with diseases can be determined. Such information will provide insights into the basic disorders as well as provide direction as to the proper therapy of such patients.
Up to 20 normal volunteers will be recruited and 30 patients. Ages will be 18 and older.
IRB Review:
Type of Review: Expedited
Most Recent Approval: January 25, 1995
Number of Human Subjects in the Last Reporting Period for this Project: 0
(Reporting periods vary.)
Type of Human Subjects Involvement:
TITLE: "Study of hemodynamics and metabolism with compounds labeled with short-lived positron emitting radionuclides (heart)". The PI on this project is Heinrich R. Schelbert, M.D.
The objective of these study protocols is to develop non-invasive techniques for accurate and specific measurements of regional myocardial metabolism and blood flow. This information will potentially be useful for early diagnosis and acquisition of highly specific information that is of potential clinical value for early disease detection, characterization of extent and severity of disease, and patient management. These studies will include evaluation and measurement of myocardial blood flow (with nitrogen-13 ammonia, rubidium-82 or oxygen-15 carbon monoxide), myocardial fatty acid metabolism (with carbon(C)-11 palmitic acid), and/or regional myocardial glucose utilization (with F-18 fluorodeoxyglucose) as well as of myocardial oxidative metabolism (with C-11 acetate). These studies will be performed in normal volunteers and in patients with cardiovascular disease (i.e., with coronary artery disease, ischemic heart disease and/or cardiomyopathy).
The tracer amounts of radioactivity used are well within the guidelines for permissible exposure. Additional potential risks include blood sampling.
We expect to study 100 patients and 50 normal subjects, male and female. Ages will be 18 or older.
IRB Review:
Type of Review: Expedited
Most Recent Approval: December 29, 1994
Number of Human Subjects in the Last Reporting Period for this Project: 0
(Reporting periods vary.)
Type of Human Subjects Involvement:
TITLE: "Determination of local myocardial amino acid utilization in man by means of N-13 labeled amino acids (and by single pass uptake) and positron emission tomography". The PI on this project is Johannes Czernin, M.D. No studies were performed in FY95.
This study is concerned with gaining a better understanding of how the heart muscle uses amino acids. Radioactive amino acids, such as glutamate, glutamine, and/or alanine, will be injected into patients and normal volunteers in order to determine potentially different distribution of amino acids between normal and ischemic myocardium. The usefulness of amino acids as an imaging agent for local ischemia or locally disturbed amino acid metabolism will be studied using PET. Early studies have indicated that amino acid levels in the myocardium vary in patients with coronary artery disease. There have been some indications that certain amino acids may be a protective agent on ischemic myocardium.
The study of amino acid metabolism may provide new insights into myocardial amino acid utilization under both normal and ischemic conditions, which would be useful in identifying metabolically altered segments of the heart. After injection of a tracer amount of radioactive amino acid, heart scans will be performed immediately in a series of images of a period of 20-30 minutes. During this time, blood samples will be obtained.
The tracer amounts of radioactivity used are well within permissible guidelines. Additional potential risks include blood sampling.
We expect to study 50 patients with suspected cardiac disease and 20 normal subjects, male and female. Ages will be 18 and order.
Radionuclides injected into arm: N-13 Glutamate, Glutamine, Alanine.
IRB Review:
Type of Review: Expedited
Most Recent Approval: February 03, 1994
Number of Human Subjects in the Last Reporting Period for this Project: 53
(Reporting periods vary.)
Type of Human Subjects Involvement:
TITLE: "Noninvasive quantification of regional myocardial blood flow reserve and glucose metabolism by myocardial imaging during dipyridamole or adenosine hypermia". The PI on this project is Heinrich R. Schelbert, M.D.
The objectives of this research proposal include investigation of the effect of maximal coronary artery vasodilation on regional myocardial blood flow and metabolism in patients with suspected or known coronary artery disease and in normal volunteers. This research will attempt not only to investigate the pathophysiology of maximal coronary artery vasodilation but also to determine whether high-risk patients can be identified so that irreversible myocardial damage can be prevented.
Significant coronary artery disease and myocardial disease remain undetected until the occurrence of a catastrophic event such as sudden death or acute myocardial infarction. Even when angina or congestive symptoms herald the presence of significant disease, accurate, predictive diagnostic tools are not currently available to determine which patients require immediate aggressive intervention in order to prevent irreversible myocardial damage.
The quantification of myocardial blood flow, oxygen consumption and myocardial metabolism in cardiac disease is of considerable clinical interest. Such measurements are important in order to gain insights into disease mechanisms for assessing diagnostic and therapeutic efficacy. PET is the only technique at this time which can noninvasively assess regional myocardial metabolism. Although perfusion defects may be observed under conditions of rest, the detection of a hemodynamic significant coronary artery lesion frequently requires conditions of increased myocardial workload and hence, blood flow. Pharmacological coronary vasodilation is an alternative to exercise. One pharmacological stress agent proven in more than 1,000 patients with PET and thallium-201 (Tl-201) imaging for the diagnosis of coronary artery disease is dipyridamole. Adenosine is a relatively new potent coronary vasodilator with clear potential as a pharmacological stress agent in cardiac imaging. Its rapid onset of action and extremely short elimination half-life suggest it may be superior to dipyridamole in this regard.
The tracer amounts of radioactivity used are well within the guidelines for permissible exposure. Additional potential risks include blood sampling.
We expect to study 500 patients with proven/suspected cardiac disease and 100 normal subjects, male and female, ages 18 and older.
Radionuclides injected into arm or inhaled: Nitrogen-13 ammonia; Carbon-11 palmitate/acetate; Fluorine-18-deoxyglucose; Oxygen-15, water, carbon monoxide, carbon dioxide.
IRB Review:
Type of Review: Expedited
Most Recent Approval: August 24, 1995
Number of Human Subjects in the Last Reporting Period for this Project: 0
(Reporting periods vary.)
Type of Human Subjects Involvement:
TITLE: "Measurement of local cerebral glucose utilization in man by means of F-18 fluorodeoxyglucose and radionuclide computed tomography". Please note that the PI on this project has been changed from John Mazziotta, M.D., Ph.D. to Sam Gambhir, M.D., Ph.D., and Carl Hoh, M.D. No subjects were seen in FY95.
PET methods using the radioactive tracer known as F-18 fluorodeoxyglucose (FDG) make it possible to construct images showing the use of sugar in different parts of the brain. These images provide unique insights into normal brain function and the disruption of normal brain function in disease states including epilepsy, cerebral palsy, learning disorders, depression, and head trauma.
The basic procedure involves injection of a small amount of FDG into a vein in the subject's arm. The subject rests quietly for 40 minutes while the sugar is being taken up by cells in the body including those in the brain. After this uptake period, images are collected for 30-60 minutes while the subject rests quietly. When certain quantitative results are needed to interpret the images, up to 50 cc of arterial or venous blood may be collected from subjects through a small catheter placed in the subject's arm. (Cardiac imaging will be offered only to the pediatric epilepsy patients with normal hearts. The heart images will be made while the FDG injection comes to equilibrium during this 30-60 minute period.)
The tracer amounts of radioactivity used are well within the guidelines for permissible exposure. Additional potential risks include blood sampling.
Approximately 350 patients and 80 normal volunteer subjects will be studied over the course of the protocol. Patients will be male and female, neonates and older. Normal male volunteers will be age 18 and older.
Radionuclides used: Fluorine-18 deoxyglucose.
IRB Review:
Type of Review: Expedited
Most Recent Approval: August 27, 1995
Number of Human Subjects in the Last Reporting Period for this Project: 0
(Reporting periods vary.)
Type of Human Subjects Involvement:
TITLE: "Positron tomography: exercise induced cardiac ischemia". The PI on this project is Janine Krivokapich, M.D.
This study is designed to investigate non-invasively the hemodynamic and metabolic effects which are elicited with stress-induced ischemia using positron emission tomography (PET). Stress will be induced with exercise, with an intravenous infusion of dobutamine, or with an intravenous infusion of dipyridamole. The tracers will be used in various combinations to characterize the acute and delayed effects of myocardial ischemia induced by stress on metabolism. Insight into the metabolic characteristics of the stunned myocardium should result.
The tracer amounts of radioactivity used are well within the guidelines for permissible exposure. Additional potential risks include blood sampling. We expect to study 35 patients with known/suspected cardiac disease and 15 normal volunteers, male and female. Ages will be 18 and older.
Radionuclides injected into arm: nitrogen-13 ammonia/glutamate; Fluorine-18 deoxyglucose; Carbon-11 Acetate/Palmitate.
IRB Review:
Type of Review: Expedited
Most Recent Approval: January 26, 1995
Number of Human Subjects in the Last Reporting Period for this Project: 0
(Reporting periods vary.)
Type of Human Subjects Involvement:
TITLE: "In-vivo measurement of regional myocardial blood flow and metabolism at different cardiac workloads using tracers of blood flow and metabolism with positron emission tomography". The PI's on this project are Heinrich R. Schelbert, M.D. and Johannes Czernin, M.D. No studies were performed in FY95.
This study investigates blood flow and metabolism at different cardiac workloads in patients with coronary artery disease. In addition, patients with other cardiac diseases, such as hypertrophic or dilated cardiomyopathy, will be studied, and normal values determined in volunteers. Methods of increasing cardiac workload and/or demand that will be utilized include exercise, intravenous dipyridamole, dobutamine and pacing. Pacing will not be utilized in normal volunteers. This study will provide improvement in the non-invasive diagnosis and characterization of cardiovascular disease and better understanding of the human heart's physiology and pathophysiology.
A baseline PET imaging study will be obtained following the first group of injections of the tracers. Cardiac workload and/or demand will be increased by exercise (walking on a treadmill or using a cycle ergometer), intravenous dipyridamole, intravenous dobutamine or pacing, and a second study will be obtained following the second group of injections of the tracers. The study may include arterial or venous blood sampling.
Echocardiography will be performed during dobutamine stimulation in healthy subjects as well as in patients with coronary artery disease, to evaluate changes in regional wall motion induced by pharmacologic stress.
The protocol will be performed on 20 patients per year, both male and female, age 18 or older, and 10 normal volunteers per year, both male and female, age 18 or older.
The tracer amounts of radioactivity used are well within permissible guidelines for exposure. Additional potential risks include blood sampling, discomfort to the patient due to rapid arterial pacing or mild chest pain in patients with coronary artery disease.
Radionuclides used: Rubidium-82 chloride; Nitrogen-13 ammonia; Carbon-11 acetate or palmitate; Fluorine-18 deoxyglucose.
IRB Review:
Type of Review: Expedited
Most Recent Approval: April 16, 1995
Number of Human Subjects in the Last Reporting Period for this Project: 0
(Reporting periods vary.)
Type of Human Subjects Involvement:
TITLE: "Tomographic measurement of local protein synthesis in man with carbon-11 leucine, phenylalanine, methionine, and/or nitrogen-13 leucine". The PI on this project is Heinrich R. Schelbert, M.D. No studies were performed in FY95.
The research plan is two-fold: The plan for the brain protocol will verify the technique in normal subjects and will examine the usefulness and effectiveness of the technique in patients with stroke and partial epilepsy to examine the alterations in local protein synthesis due to these disorders. The research plan for the heart protocol will explore the possibility of quantifying regional rates of protein synthesis in myocardium with positron emission tomography (PET) and labeled amino acids in normal subjects and in patients with heart disease.
Labeled amino acids will be injected into the subjects and imaging will be done by PET. Blood samples will be withdrawn at intervals during the imaging process. Risks to the subjects are minimal: the radiation dose is small and well within prescribed limits; the tracer is a natural amino acid that is present in plasma; and arterial and venous sampling has been done for years without complications.
70 patients and 30 normal subjects, male and female, will be studied. The age of the epilepsy patients will be newborn up; others will be 18 or older.
Radionuclides used: Carbon-11 Leucine, Phenylalanine, Methionine, and/or Nitrogen-13 Leucine.
IRB Review:
Type of Review: Full Board
Most Recent Approval: August 07, 1995
Number of Human Subjects in the Last Reporting Period for this Project: 0
(Reporting periods vary.)
Type of Human Subjects Involvement:
TITLE: "Dopamine transport and storage measured with 4-[18F] fluoro-L-metatyrosine". The PI's on this project are Jorge Barrio, Ph.D. and Sam Gambhir, M.D., Ph.D.
The objective of this study is to perform in vivo quantitative measurements of regional L-DOPA transport and storage in the brain of human subjects using Positron Emission Tomography (PET), both in normal volunteers and patients with certain neurological and psychiatric disorders. Abnormalities in the dopamine system with changes in dopamine receptor binding have been demonstrated in animal models and human autopsy studies of many neurological and psychiatric illnesses. Over recent years, major institutions throughout the world have developed radiopharmaceuticals to label precursors of dopamine in the living human brain.
Initially, the use of 4-FMT will be directed at control subjects of both sexes with ages greater than 19. These subjects will provide a database for the distribution, magnitude and range for quantitative values for 6-FMT in the normal brain at various ages. From this database, we will compare patients with a variety of disorders, including epilepsy, Huntington's disease, tardive dyskinesia, Parkinson's disease, progressive supranuclear palsy, dystonia, affective disorders, schizophrenia, Gilles de La Tourette syndrome, obsessive compulsive disorders, individuals exposed to toxins that may produce Parkinsonian-like symptoms (e.g., MPTP, carbon monoxide, manganese), and others.
Thirty normal volunteers and thirty patients will be studied initially.