Dr. David
Eisenberg
Box 951570
Los Angeles, CA 90095-1570
Phone: 310-825-3754
Fax: 310-206-3914
E-mail: david@pauling.mbi.ucla.edu
Number of Human Subjects projects reported: 10
Project Identifier:
UCLA-92-640
Project Title:
"Dopamine Transport and Storage Measured with DOPA"
Principal Investigator: Dr. Gary W. Small, University of California, Los Angeles
Project started in: 1992
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Identifier or number: UCLA1-92-640
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Most recent IRB approval: 02/05/99
IRB approval number: 92-11-640-12
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 1999 (10/1/98-9/30/99)
Type(s) of Human Subjects Involvement:
Dopamine is a major neurotransmitter in the central nervous system that is involved in mediating thoughts, emotions and motor behaviors. L-DOPA, which we have labeled with 18F, is a precursor in the synthesis of dopamine. By injecting trace amounts of 18F-L-DOPA in subjects and using PET technologies, we are able to measure the rates at which the dopamine neurons synthesize and excrete dopamine. MRI scans and drawing blood samples for genetic analysis has been added to the protocol this past year. If genetic links can be found, it may be possible to diagnose a brain disorder before symptoms develop.
Cocaine produces its euphoric effects, at least in part, through its effects on the dopamine neuron. Other substances of abuse, such as alcohol and opiates, may have dopamine mechanisms too. In Parkinson's disease, the dopamine neurons are slowly destroyed. With continued cocaine or amphetamine use in animals, there is evidence for damage of the dopamine secreting neurons. Our PET studies so far in humans and monkeys have also shown this. Drug abusers trying to synthesize narcotics in Northern California a number of years ago accidentally made a compound (referred to as MPTP) that induced Parkinson's disease.
We are doing fluorodopa PET scans of Parkinson's disease patients, cocaine abusers, amphetamine abusers, opiate abusers with and without MPTP exposure, alcoholics, and normal controls to better understand the effects of these drugs on the presynaptic dopamine neuron. Damage that these patients sustained to their dopamine system may explain their difficulty in getting off of drugs. Subjects undergo fluorodopa scanning after first stopping the drug, and then after at least 6 months abstinence, to see if there is any recovery. We correlate the findings with their symptoms. We are doing parallel studies in monkeys where drug use and amounts can be controlled to better understand this problem. Drug abusers come from UCLA Neuropsychiatric Hospital and populations. MPTP exposed individuals are sometimes referred by Dr. William Langston in San Jose. Patients who are not UCLA outpatients come into the Clinical Research Center (CRC) in San Jose under an approved CRC protocol.
Risks include: from exposure to radiation, the dose received from this study is well below the levels that are thought to result in a significant risk of harmful effects; from injection of radiopharmaceutical, side effects in some people including muscle stiffness, involuntary movements of the eyes, or restlessness; from blood sampling, slight discomfort from the needle, lightheadedness, fainting, soreness and discoloration; from arterial blood samples, shortness of breath, allergic reaction and low blood pressure from the local anesthetic agent, arterial spasm causing cold or painful hands, tenderness at site of the tube insertion; from the MRI, anxiety and attraction of certain metals to the magnetism of the machine.
The identity of the participants in this research study will remain confidential. Any identifying information will be securely locked in a file cabinet, and only personnel related to the study will have access to these records. No information that identifies any participant will be released without that subject's separate consent, except as specifically required by law.
Project Identifier:
UCLA-93-654
Project Title:
"Assessment of Myocardial Viability by N-13 Ammonia, F-18 Deoxyglucose and Positron Emission Tomography"
Principal Investigator: Dr. Heinrich R. Schelbert, University of California, Los Angeles
Project started in: 1993
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Identifier or number: UCLA1-93-654
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Most recent IRB approval: 04/09/99
IRB approval number: 93-11-654-13
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 1999 (10/1/98-9/30/99)
Type(s) of Human Subjects Involvement:
This study seeks to define noninvasively the presence of viable myocardium in patients with coronary artery disease using Positron Emission Tomography (PET) and radiotracers of blood flow (N-13 ammonia) and glucose metabolism (F-18 deoxyglucose). Myocardial viability denotes heart muscle that does not contract appropriately because of reduced blood flow. Importantly, such heart muscle can regain its function if blood flow is restored by coronary artery bypass surgery or balloon angioplasty. Such viable myocardium differs distinctly from myocardium that has sustained permanent damage; the loss or impairment of contraction is irreversible even if blood flow were to be restored. Identification of patients with viable myocardium is, thus, important because of potential benefits from bypass surgery. Patients with large amounts of viable myocardium are likely to improve symptomatically, are physically more active and can live a more active life after surgical revascularization. Identification of viable myocardium, thus, becomes clinically important in many patients with a diminished pumping function of the heart because in many instances the only alternative treatment is cardiac transplantation.
The objective of Study Protocol A is to determine the amount of viable myocardium, and how this amount can predict an improvement in the patient's symptoms after surgical bypass grafting. In 50 patients with coronary artery disease, blood flow to the heart muscle will be measured with the radiotracer N-13 ammonia and glucose metabolism of the heart with the radiotracer F-18 deoxyglucose. Both measurements will be done at rest while the patient is in the Nuclear Medicine imaging scanner. To establish normal values, an additional 15 normal volunteers will be studied in an identical fashion. Under Study Protocol B, another 30 patients with coronary artery disease will be examined in a similar fashion, except for one additional measurement of blood flow following administration of a drug (dipyridamole) which maximally increases flow to the heart. Because such increases will be diminished in coronary artery disease, this additional measurement yields information on the presence of additional coronary artery disease and its severity. Thus, the objective of this part of the protocol is to determine whether severe coronary artery disease accounts for a loss in the contractile function of the heart muscle with normal blood flow at rest. These studies, to be performed with N-13 ammonia and F-18 deoxyglucose and PET or with dipyridamole, are well established standard examinations in nuclear medicine. Physician investigators conducting these studies are certified in advanced cardiac life support. Study Protocol A will require approximately 3 hours and Study Protocol B approximately 4 hours for completion in each subject. The information obtained in each patient may be of direct medical benefit. A total of 80 patients and 30 healthy volunteers will be enrolled.
Participants will be exposed to risks from venous blood sampling (slight discomfort); the administration of N-13 ammonia (discomfort, lightheadedness, fainting, bruising, or none of these); exposure to a small amount of radiation (well below the levels that result in risks of harmful effects); the cold pressor test (may cause mild to severe pain of the hand which quickly subsides or coronary spasm in rare cases); slow heart rate which can be reversed by intravenous administration of atropine; dipyridamole (flushed feeling, mild headache, nausea, shortness of breath, irregular heart beat, hypotension or dizziness for a short while). People who suffer from bronchial asthma cannot participate in this study because asthma is a contra-indication for intravenous administration of dipyridamole.
The identity of the participants in this research study will remain confidential. Any identifying information will be securely locked in a file cabinet, and only personnel related to the study will have access to these records. No information that identifies any participant will be released without the participant's separate consent, except as specifically required by law.
Project Identifier:
UCLA-95-117
Project Title:
"Measurement of Myocardial Blood Flow with N-13 Ammonia"
Principal Investigator: Dr. Heinrich R. Schelbert, University of California, Los Angeles
Project started in: 1995
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Identifier or number: UCLA1-95-117
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Most recent IRB approval: 09/23/99
IRB approval number: 95-03-117-11
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 52
Reporting period for number of human subjects:
Fiscal Year 1999 (10/1/98-9/30/99)
Type(s) of Human Subjects Involvement:
Co-investigator is Johannes Czernin, MD.
The aim of this study is to determine, noninvasively, coronary artery disease in healthy subjects, individuals at risk, and patients with the disease, using Positron Emission Tomography (PET). PET can assess these problems noninvasively and can identify individuals with early abnormalities in coronary vasomotion or endothelial function. This is of importance because lifestyle modifications, such as smoking cessation or a low lipid diet, might reverse the course of the disease.
All subjects will undergo PET imaging of the heart at rest and during cold pressor stress under baseline conditions and during intravenous L-arginine. L-arginine, a physiologically occurring amino acid, is a precursor of nitric oxide and might induce a small increase in the blood flow to the heart. L-arginine is used clinically to test the pituitary function.
The cold pressor test will be performed by immersing the patient's hand in ice water for about 2 minutes. Cold pressor testing induces a modest increase in heart rate and systolic blood pressure, and is, therefore, considered a very mild stressor.
On the first day, radioisotope N-13 ammonia will be injected when the subject is at rest, and then again during cold pressor testing.
On the second day, the radioisotope N-13 ammonia will be injected when the subject is at rest with the simultaneous application of intravenous L-arginine.
On the third day, the radioisotope N-13 ammonia will be injected during cold pressor testing with the simultaneous application of intravenous L-arginine.
Patients aged 18 years or older, males and nonpregnant females after giving written consent and proving to be within the study criteria will be accepted in the study.
Normal control subjects ages 18 years and older, male and nonpregnant females will be given a normal resting electrocardiogram after giving written consent and proving to be within the study criteria will be accepted in the study.
Twenty normal controls and 40 patient volunteers will be studied.
This is an open trial.
Johannes Czernin, MD., Assistant Professor Nuclear Medicine and H.R. Schelbert, MD., Professor Pharmacology/Nuclear Medicine will be responsible for this research. The research will be conducted in the PET Center, AR-115, CHS, UCLA.
Participants will be exposed to risks from venous blood sampling (slight discomfort); the administration of N-13 ammonia (discomfort, lightheadedness, fainting, bruising, or none of these); exposure to a small amount of radiation (well below the levels that result in risks of harmful effects); the cold pressor test (may cause mild to severe pain of the hand which quickly subsides or coronary spasm in rare cases, slow heart rate which can be reversed by intravenous administration of atropine); dipyridamole (flushed feeling, mild headache, nausea, shortness of breath, irregular heart beat, hypotension or dizziness for a short while). People who suffer from bronchial asthma cannot participate in this study because asthma is a contra-indication for intravenous administration of dipyridamole.
The identity of the participants in this research study will remain confidential. Any identifying information will be securely locked in a file cabinet, and only personnel related to the study will have access to these records. No information that identifies any participant will be released without the participant's separate consent, except as specifically required by law.
Project Identifier:
UCLA-95-450
Project Title:
"Significance of Cardiac Allograft Vasculopathy"
Principal Investigator: Dr. Johannes Czernin, University of California, Los Angeles
Project started in: 1995
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Identifier or number: UCLA1-95-450
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Most recent IRB approval: 11/23/98
IRB approval number: 95-10-450-04
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 1999 (10/1/98-9/30/99)
Type(s) of Human Subjects Involvement:
Study #1
The aim of this study is to determine, noninvasively with positron emission tomography (PET) the effects the amino acid L-arginine on myocardial blood flow and flow reserve in cardiac transplant recipients. PET can assess these problems noninvasively and can identify individuals with early abnormalities in coronary vasomotion or endothelial function. This is of importance because early abnormalities in coronary vasomotion and blood flow might be reversible, indicating that transplant vasculopathy is a reversible process.
All subjects will undergo PET imaging of the heart at rest and during cold pressor stress under baseline conditions and during intravenous L-arginine. L-arginine, a physiologically occurring amino acid, is a precursor of nitric oxide and might induce a small increase in the blood flow to the heart. L-arginine is used clinically to test the pituitary function.
The cold pressor test will be performed by immersing the patients hand in ice water for about 2 minutes. Cold pressor testing induces a modest increase in heart rate and systolic blood pressure and is therefore considered a very mild stressor.
On the first day, the radioisotope N-13 ammonia will be injected when the subject is at rest, and then again during cold pressor testing while the amino acid L-arginine is infused for 45 minutes.
On the second day, the cold pressor test will be performed first followed by the radioisotope injection when the patient is at rest with the simultaneous application of intravenous L-arginine.
Patients aged 18 years or older, males and nonpregnant females after giving written consent and proving to be within the study criteria will be accepted in the study.
Normal control subjects ages 18 years and older, male and nonpregnant females will be given a normal resting electrocardiogram after giving written consent and proving to be within the study criteria will be accepted in the study.
Twenty normal controls and 20 transplant recipients will be studied.
This is an open trial.
Johannes Czernin, MD, Assistant Professor, Nuclear of Medicine will be responsible for this research. The research will be conducted in the PET Center, AR-115, CHS, UCLA.
Study #2
The aim of this study is to determine, noninvasively, in cardiac transplant recipients the presence and severity of transplant coronary artery disease using Positron Emission Tomography (PET). In addition, early abnormalities in the blood flow to the heart will be determined and related to future clinical events, such as recurrent heart failure or sudden cardiac death. Patients will undergo N-13 ammonia PET at rest, during cold pressor testing and during intravenous dipyridamole.
PET can assess blood flow to the heart noninvasively and can identify individuals with early abnormalities in coronary vasomotion. This is of importance because such abnormalities might precede transplant coronary artery disease, and might be modulated by acute or chronic pharmacologic interventions.
A total of 300 cardiac transplant recipients will be studied for this 5-year study: 60 patients/year within 4-6 weeks after cardiac transplantation. They will be restudied annually for 5 years.
The cold pressor test will be performed by immersing the patient's hand in ice water for about 2 minutes. Cold pressor testing induces a modest increase in heart rate and systolic blood pressure, and is, therefore, considered a very mild stressor. Dipyridamole, a commonly used pharmacologic stress agent, will be given intravenously at a rate of 0.56 mg/kg over 4 minutes.
Patients aged 18 years or older, males and nonpregnant females after giving written consent and proving to be within the study criteria will be accepted in the study.
Normal control subjects ages 18 years and older, male and nonpregnant females will be given a normal resting electrocardiogram, after giving written consent, and proving to be within the study criteria will be accepted in the study.
Twenty normal controls and 60 transplant recipients/year will be studied.
This is an open trial.
Johannes Czernin, MD., Assistant Professor Nuclear Medicine. The research will be conducted in the PET Center, AR-115, CHS, UCLA.
For study #1 and #2, the participants will be exposed to risks from venous blood sampling (slight discomfort); the administration of N-13 ammonia (discomfort, lightheadedness, fainting, bruising, or none of these); exposure to a small amount of radiation (well below the levels that result in risks of harmful effects); the cold pressor test (may cause mild to severe pain of the hand which quickly subsides or coronary spasm in rare cases, slow heart rate which can be reversed by intravenous administration of atropine); dipyridamole (flushed feeling, mild headache, nausea, shortness of breath, irregular heart beat, hypotension or dizziness for a short while). People who suffer from bronchial asthma cannot participate in this study because asthma is a contra-indication for intravenous administration of dipyridamole.
The identity of the participants in this research study will remain confidential. Any identifying information will be securely locked in a file cabinet, and only personnel related to the study will have access to these records. No information that identifies any participant will be released without the participant's separate consent except, as specifically required by law.
Project Identifier:
UCLA-96-082
Project Title:
"Sparing/Recovery of Function after Hemispherectomy: Analysis with Functional Imaging"
Principal Investigator: Dr. Sanjiv Gambhir, University of California, Los Angeles
Project started in: 1996
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Identifier or number: UCLA1-96-082
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Most recent IRB approval: 04/30/98
IRB approval number: 96-02-082-03
Explanation of IRB approval:
This project was inactive in FY1999. The last IRB approval was for 4/30/98. No subjects were studied and the project is pending.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Year prior to last IRB approval date
Type(s) of Human Subjects Involvement:
Co-investigators are Harley Kornblum, MD., Ph.D., and Sarah Copeland, Ph.D.
The objective of this study is to examine patterns of cerebral blood flow during rest or during movement or sensory stimulation using positron emission tomography (PET), and functional magnetic resonance imaging (fMRI). The goal of this project is to investigate the mechanisms that allow subjects to retain certain motor and sensory abilities after cerebral hemispherectomy, the removal of the cerebral cortex of an entire hemisphere. If this surgery is performed at an early age (typically prior to 7-8 years), sensory and motor performance is usually better than the performance seen after damage in adulthood. Although some motor deficits remain following surgery (e.g., the loss of fine finger movements and foot tapping), gross motor performance (e.g., walking) can be relatively spared. Despite the presence of some sensory deficits, evidence exists, though not yet determined, for the preservation of these functions after early brain damage in humans, although they may involve recruitment of some already existing motor pathways, and/or formation of new connections between the remaining hemisphere and subcortical structures involved in the control of movement on the affected side. Both of these mechanisms have been shown to play roles in the recovery of function after hemispherectomy in cats and rats. In this study, patterns of cerebral activation during movement and sensory stimulation of the affected and unaffected limbs in patients and of the two limbs in normal control volunteers will be related to the recovery of motor and sensory function after hemispherectomy.
A brief neurological examination will be administered to each patient prior to scanning. Additionally, handedness will be assessed by means of a standard questionnaire. Subsequently, functional neuroimaging techniques will be employed to examine areas activated during motor performance and sensory stimulation in patients and normal volunteers. For PET studies, each scan will involve an injection of radioactive water, which will be adjusted for the subject's weight. A single session will consist of 5-7 scans, with 3 baseline (resting) scans and 2-3 activation scans for the right and left limbs in either a sensory or motor activation condition. Motor activation tasks will consist of simple, repetitive arm or leg movements, and sensory conditions will involve repeated sensory stimulation of an arm or leg. MRI sessions will include a set of scans to obtain images of brain anatomy that will be used for co-registration of PET and fMRI data, and a set of functional MRI images obtained during both rest and the same activation conditions as are used in PET scans. Both of these functional imaging techniques are designed to demonstrate areas of local cerebral blood flow increase in the brain during activation.
The study population will consist of up to 40 patients, both male and female, ranging in age from 10 to 25 years, who have undergone cerebral hemispherectomy for epilepsy at the UCLA Medical Center. After HSPC approval, an ad will be placed in local newspapers to solicit up to 40 volunteers aged 18 or over, and they will be matched with subjects for gender to serve as a control population. Control subjects will be neurologically normal, and not on medication. Any subject who is suspected of being pregnant will be excluded from the study. We propose to reimburse the volunteers at the rate of $25/hour for involvement in the procedures described above. The volunteers will be asked to read and sign the enclosed normal volunteer consent forms that will be explained to them in detail by one of the investigators. Patients will also be asked to read and sign the patient consent forms, or in the case of patients under age 12, the child assent forms.
Sam Gambhir, MD., Ph.D., Harley Kornblum, MD., Ph.D, and Sarah Copeland, Ph.D., will be conducting the research and will be responsible for obtaining informed consent from all subjects. PET scanning will be conducted at the UCLA clinical PET center (CHS A-level), and MRI scanning will take place either at the UCLA clinical MRI suite (CHS B-level) or at 200 Medical Plaza.
Risks include: from exposure to radiation, the dose received from this study is well below the levels that are thought to result in a significant risk of harmful effect; from injection of the radiopharmaceutical, side effects in some people including muscle stiffness, involuntary movements of the eyes, or restlessness; for blood sampling, slight discomfort from the needle, lightheadedness, fainting, soreness and discoloration; from the MRI, anxiety and attraction of certain metals to the magnetism of the machine.
The identity of the participants in this research study will remain confidential. Any identifying information will be securely locked in a file cabinet, and only personnel related to the study will have access to these records. No information that identifies any participant will be released without the participant's separate consent, except as specifically required by law.
Project Identifier:
UCLA-96-426
Project Title:
"Response of Coronary Vasomotion to Intravenous L-Arginine"
Principal Investigator: Dr. Heinrich Schelbert, University of California, Los Angeles
Project started in: 1996
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Identifier or number: UCLA1-96-426
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Most recent IRB approval: 02/25/99
IRB approval number: 95-09-426-03
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 1999 (10/1/98-9/30/99)
Type(s) of Human Subjects Involvement:
This three day study protocol will be performed using N-13 ammonia PET at rest (baseline), during Cold Pressor testing, during baseline and intravenous application of L-arginine and during Cold Pressor testing and intravenous L-arginine. This study is aimed at identifying early abnormalities in myocardial blood flow and their potential reversibility by intravenous application of L-arginine. Early identification of individuals with abnormal coronary vasomotion is important because these abnormalities have been shown to precede the development of coronary artery disease.
N-13 ammonia, diluted in saline, is a radiolabeled compound which will be administered intravenously. There are no known side effects of N-13 ammonia. However, the participants will be aware that a small amount of radioactivity will be involved in this study which is comparable to less than 1% of what California law deems an acceptable amount of exposure during the course of one year for a radiology technologist. Women of child bearing age will only be enrolled if they undergo a pregnancy test. Women who are or have been on contraceptive medication until 4 weeks prior to the study will be excluded from the study because estrogen might alter the baseline measurements of myocardial blood flow. However, women using a barrier method such as an intrauterine device or women who agree to take birth control pills for three months following the study will be able to participate in this study.
The cold pressor test involves the immersion of one hand in ice water for 90-120 seconds. This evokes the release of local and adrenal catecholamines resulting in a modest, about 20-30% increase in cardiac work as evidenced by modest increases in the rate pressure product (heart rate x systolic blood pressure). The most common adverse effect of cold is local pain. Other side effects occur rarely. However, episodes of low heart rate and low blood pressure have been observed. This was ascribed to increases in parasympathetic nerve activity. The side effects can be reversed promptly by the intravenous application of atropine, a drug that blocks parasympathetic activity. Cold might induce coronary vasospasm. However, the risk for vasospasm to occur is very small and not greater than induced by cold weather. Some patients with coronary artery disease might develop chest pain. If this occurs, oral nitroglycerine will be administered.
L-arginine is a physiologically occurring amino-acid. It is a known precursor of nitric oxide, a strong physiologic coronary vasodilator. It has been used to test human pituitary function. Few side effects are known. For instance, mild allergic reactions such as flushing, vomiting, headache, or numbness might occur and will pass. Other possible side effects are skin rash, swelling of the hands and the face which will be treated by anti-histamines.
Both N-13 ammonia and L-arginine will be administered intravenously. Therefore, a intravenous line (butterfly) will be placed on day I and day II and III of the study. This might be associated with local pain and a blue discoloration of the skin (hematoma).
Twenty patients with known coronary artery disease will be recruited through the division of Cardiology/Department of Medicine at UCLA. Both, the attending physician and the home officer will need to agree in writing to the participation in this study.
Twenty healthy individuals, matched in age to the patients will be recruited through advertising the study in local newspapers.
Twenty individuals with elevated total or LDL cholesterol will also be enrolled. They will be recruited through the Division of Cardiology/Department of Medicine at UCLA. Both the attending physician and the home officer will need to agree in writing to the participation of their patients in this study.
All participants will be paid $25/hour. They also will be compensated for travelling time and parking.
The Principal Investigator (Johannes Czernin, MD) will obtain the informed consent in the presence of a consent monitor provided by the volunteer office at UCLA. He will also be present throughout the entire study.
Participants will be exposed to risks from venous blood sampling (slight discomfort); the administration of N-13 ammonia (discomfort, lightheadedness, fainting, bruising, or none of these); exposure to a small amount of radiation (well below the levels that result in risks of harmful effects); the cold pressor test (may cause mild to severe pain of the hand which quickly subsides or coronary spasm in rare cases, slow heart rate which can be reversed by intravenous administration of atropine); dipyridamole (flushed feeling, mild headache, nausea, shortness of breath, irregular heart beat, hypotension or dizziness for a short while). People who suffer from bronchial asthma cannot participate in this study because asthma is a contra-indication for intravenous administration of dipyridamole.
The identity of the participants in this research study will remain confidential. Any identifying information will be securely locked in a file cabinet, and only personnel related to the study will have access to these records. No information that identifies any participant will be released without the participant's separate consent, except as specifically required by law.
Project Identifier:
UCLA-98-021
Project Title:
"Human Subject Research Under Structural Biology & Molecular Medicine Research Program"
Principal Investigator: Dr. David Eisenberg, University of California, Los Angeles
Project started in: 1998
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Identifier or number: UCLA1-98-021
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Most recent IRB approval: 10/26/98
IRB approval number: 97-10-021-02
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 1999 (10/1/98-9/30/99)
Type(s) of Human Subjects Involvement: Abstract:
This approval represents the administrative approval for human subject related research projects through the UCLA-DOE Laboratory of Structural Biology and Molecular Medicine under DOE Cooperative Agreement DE-FC03-87ER60615. The various projects represented by this approval have been listed separately in the database with their individual identifiers since this administrative approval was not put in place until FY1998.
Project Identifier:
UCLA-98-039
Project Title:
"Beta-Amyloid Probes of Alzheimer's Disease"
Principal Investigator: Dr. Gary W. Small, University of California, Los Angeles
Project started in: 1998
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Identifier or number: UCLA1-98-039
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Most recent IRB approval: 09/16/99
IRB approval number: 97-07-039-03
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 5
Reporting period for number of human subjects:
Fiscal Year 1999 (10/1/98-9/30/99)
Type(s) of Human Subjects Involvement:
Current methods of imaging brain function can show patterns of brain activity that are characteristic of Alzheimer's disease, including decreased brain activity in areas known to be involved in memory function. These approaches may show such abnormalities early in the course of the disease. However, the current methods provide measures of general brain function rather than measures specific to the disease process. In order to develop disease-specific brain measures, we measure the concentration of a neuropathological hallmark of the disease, the amyloid plaque. Small molecules labeled with fluorine-18, which can be measured using positron emission tomography (PET) imaging, will be used in the study. After determining the safety of these small molecules, we will inject a small amount into a subject's blood stream and then use PET imaging to determine the molecule's concentration in different regions of the brain. Patients with Alzheimer's disease will be compared with age-matched persons without cognitive impairment. This approach may facilitate a brain imaging test that shows specific patterns that predict the development of Alzheimer's disease, making it useful in identifying persons who would be candidates for new anti-dementia treatments.
The data will be collected by a PET scanning device. Image data will be stored on optical disks. Patient charts with personal identifiers will be kept in a securely locked file cabinet in a locked room to which only the investigators have access.
No severe substantial risks are anticipated. The examination will expose the subjects to a very small amount of radiation, which is not expected to cause any adverse effects. The procedure is associated with the placement of a small IV line. Placing this line might cause some discomfort, dizziness, fainting. In rare instances, infection or bleeding might occur. However, this is unlikely since sterile and standard medical practices will be used, and the discomforts are no different from those encountered during a routine blood test or blood donation.
The identity of the participants in this research study will remain confidential. Any identifying information will be securely locked in a file cabinet, and only personnel related to the study will have access to these records. No information that identifies any participant will be released without the participant's separate consent, except as specifically required by law.
Project Identifier:
UCLA-98-062
Project Title:
"FDG PET for Evaluating Patients with a Pelvic Mass"
Principal Investigator: Dr. Johannes Czernin, University of California, Los Angeles
Project started in: 1998
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Identifier or number: UCLA1-98-062
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Most recent IRB approval: 09/23/99
IRB approval number: 98-03-062-02
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 5
Reporting period for number of human subjects:
Other: 07/09/98 to 07/08/99
Explanation:
IRB approval in FY1998 was approved 7/9/98 but was not activated until after this database was updated. This is the second year of the approval.
Type(s) of Human Subjects Involvement:
Cancers of the ovaries constitute a major portion of all pelvic masses and continue to be a major health problem in the United States. Approximately 20,000 new cases of ovarian cancer occur annually in the United States and about 60% of women with ovarian cancer will succumb to this disease within 5 years of the diagnosis. Ovarian cancer is currently the 6th most common cancer in the United States and the 4th most common cause of female cancer deaths, ranking behind lung, breast and colon cancer. Five-year survival rates have been disappointingly stable at a low level of about 35-40% despite the use of aggressive chemotheraphy, second-look surgery and salvage therapies including radiation, intraperitoneal chemotherapy, and the use of investigational agents. In post-menopausal women, about 30-40% of all pelvic masses by ultrasound are identified as malignant during surgical exploration, indicating that 60-70% of these interventions would be unnecessary if ovarian cancer could have been ruled out prior to surgery. The presurgical evaluation of a pelvic mass has largely relied on the use of physical pelvic examination, ultrasound and computed tomography. Different size and morphological criteria have been established to determine the nature of the pelvic mass. However, the diagnostic accuracy of pelvic examination and transvaginal ultrasound to predict the nature of a pelvic mass are equally disappointing. Thus, the standard approach for evaluating pelvic masses in post-menopausal women remains exploratory surgery, and most gynecologists remain uncomfortable, adopting a wait and see policy. A correct presurgical diagnosis would therefore be desirable to avoid exploratory surgery in women with benign pelvic disease.
Positron emission tomography (PET) is a form of computer-assisted imaging which produces images that show body function, for instance glucose metabolism of tumors. Using this technique together with an isotope called F-18 deoxyglucose (FDG) allows the imaging of tumor metabolism in patients with cancer. FDG-PET imaging utilizes the accelerated rate of glucose consumption characteristic of malignant tissue. Whole body PET-imaging together with FDG detects accurately and safely many different cancers including lung cancer, thyroid cancer, breast cancer, melanoma, lymphoma, squamous cell carcinomas of the head and neck region, colon cancer and musculo-skeletal tumors. Although PET-FDG cannot replace surgery in the detection of microscopic recurrence, it can accurately detect tumors greater than 1.0 cm in diameter. Preliminary data suggest that FDG-PET might aid in the presurgical diagnosis of pelvic masses. Such diagnosis might eventually alter patient management if FDG-PET imaging can differentiate relaibly between benign and malignant disease.
After surgical removal, patients with ovarian cancer are followed by determining the serum levels of the tumor marker CA-125. Increases in CA-125 suggest recurrence of disease and are frequently followed by several anatomic imaging studies such as CT-scans of the pelvis and abdomen. However, postsurgical scarring precludes the exact determination of the site of recurrence as well as the extent of disease by anatomical imaging modalities such as CT or ultrasound. PET imaging might overcome these limitations since functional changes such as increases in glucose metabolic activity in malignant tissue are observable independent of structural alterations.
The current pilot study, which will not alter the clinical management of the study population, consists of two parts:
a) Fifty postmenopausal women with evidence of a pelvic mass by pelvic examination, transvaginal ultrasound and computed tomography (CT), and/or elevated serum CA-125 levels, who are scheduled for exploratory surgery, will undergo a whole body PET scan to determine the diagnostic accuracy of PET for identifying malignancy.
b) Fifty patients with ovarian cancer and status post surgical removal of a pelvic mass, whose tumor markers are rising, will undergo a whole body PET scan to determine location and extent of recurrent disease.
The patho-histological findings during surgery will be used as the reference gold standard to determine the diagnostic accuracy of FDG-PET.
It should be emphasized that only the PET study should be considered research. Measurements of tumor markers, ultrasound and CT-evaluation and physical pelvic examination as well as exploratory surgery, are part of the routine work-up of patients with a pelvic mass.
Risks: This is a minimal risk study. The amount of radioactivity involved is less than that associated with a CT scan. The insertion of the i.v. line might induce pain, bleeding and, in rare instances, infection. Some research subjects might experience claustrophobia during the imaging procedure.
Confidentiality: The identity of the participants in this research study will remain confidential. Any identifying information will be securely locked in a file cabinet and only personnel related to the study will have access to these records. No information that identifies any participant will be released without the participant's separate consent, except as specifically required by law.
Project Identifier:
UCLA-99-061
Project Title:
"Repeat Measurements of Myocardial Blood Flow with N-13 Ammonia and PET During Cold Pressor Testing"
Principal Investigator: Dr. Heinrich R. Schelbert, University of California, Los Angeles
Project started in: 1999
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Identifier or number: UCLA1-98-061
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Most recent IRB approval: 11/09/98
IRB approval number: 98-08-061-01
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 1999 (10/1/98-9/30/99)
Type(s) of Human Subjects Involvement:
The objective of this study is to evaluate the reproducibility of cold pressor test in healthy individuals, as a non-invasive means to assess early coronary artery disease.
Background: In previous studies we have demonstrated the possibility to identify individuals with early coronary artery disease (CAD). Importantly, disease at this very early stage can be reversed or its progression be halted by changes in lifestyle and newly available medications. Individuals with evidence of early disease typically have coronary risk factors like cigarette smoking, hypertension, diabetes, high cholesterol or obesity. These "coronary risk factors" are usually responsible for the development of early CAD. Therefore, it is of interest to identify these individuals and then, to prevent future manifestations of heart disease.
Identification of early disease required until recently use of highly invasive techniques as for example coronary arteriography or intracoronary ultrasound. However, such evaluation is now possible noninvasively through measurements of myocardial blood flow with positron emission tomography (PET) and cold pressor testing (CPT). Blood flow responses to CPT can be abnormal in patients with coronary artery disease, so that this test will be useful for the detection of early CAD. Several medications are now available for the treatment of early CAD. In order to study the effects of these medications on the coronary artery, repeat measurements of blood flow are needed. Therefore, it will be important to define whether the cold pressor test when used in the same individual produces always the same change. This will be especially important for testing whether newly available medication does in fact normalize blood flow responses to cold and, by implication, reverse the very early stage of coronary artery disease.
Protocol: We will have one study group: healthy young individuals without any coronary risk factors or symptoms of CAD. We will measure myocardial blood flow with PET and a radioactive indicator (N-13 ammonia) at baseline and during CPT when the volunteer immerses the left hand in ice cold water for 90-120 seconds; this will be done on two separate days. It will give us an answer about the reproducibility of this methodology. In addition, in order to rule out the presence of fully developed CAD, we will perform one measurement of myocardial blood flow during adenosine infusion (a standard clinical test to evaluate presence of CAD) only on the first study session. By helping to identify the reproducibility of CPT, this research will provide insight into a potential new strategy for detecting early CAD in humans. Furthermore, it is anticipated to become useful for monitoring "reversal" of early coronary disease in response to treatment.
Forty healthy volunteers will be recruited for this study.
Risks: The overall risk classification of the research is minimal. Participants will be exposed to risks from venous blood sampling (slight discomfort); the administration of N-13 ammonia (discomfort, lightheadedness, fainting, bruising, or none of these); exposure to a small amount of radiation (well below the levels that result in risks of harmful effects); the cold pressor test (mild to severe pain of the hand which quickly subsides, or no pain, coronary spasm in rare cases, slow heart rate which can be reversed by intraveous administration of atropine or no effect); adenosine (flushed feeling, mild headache, nausea, dizziness, abnormal heart rhythms, palpitations, shortness of breath, fainting spells, chest pressure or chest pain for a short while after the injection, or none of these).
Confidentiality: The identity of the participants in this research study will remain confidential. Any identifying information will be securely locked in a file cabinet and only personnel related to the study will have access to these records. No information that identifies any participant will be released without the participant's separate consent, except as specifically required by law.