Dr. David Eisenberg
Box 951570
Los Angeles, CA 90095-1570
Phone: 310-825-3754
Fax: 310-206-3914
Email: david@pauling.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: 9
Project Identifier: UCLA-92-639
Project Title:
Mapping Dopamine Receptors with F-18 Fluorethylspiperone
Principal Investigator:
Dr. Gary W. Small
Project started in: 1992
Project Funding Information:
Project received funding in Fiscal Year 1997.
Project did not use human subjects in Fiscal Year 1997.
Explanation:
Project was inactive in this fiscal year; no human subjects were studied.
Funding Sources:
Funding from DOE under a cooperative agreement is for basic research in nuclear medicine, which may or may not be used for human subject research studies in a given fiscal year.
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: October 03, 1996
IRB Approval Number: 92-11-639-04
Number of Human Subjects who participated in this project/protocol during
FY 1997 (10/1/96 - 9/30/97): 0
Type of Human Subjects Involvement:
This project 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 subjects vein while sampling blood from a vein or artery. While this is happening, the subject is lying on a couch with their head in a large machine 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.
Each year, up to 20 normal and 30 patient volunteers will be recruited. Ages will be 18 and older.
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 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 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-92-640
Project Title:
Dopamine Transport and Storage Measured with DOPA
Principal Investigator:
Dr. Gary W. Small
Project started in: 1992
Project Funding Information:
Project received funding in Fiscal Year 1997.
Project did not use human subjects in Fiscal Year 1997.
Explanation:
Human subjects were studied under previous IRB approval with funding through NIH. No human subjects have yet been studied under the new IRB approval.
Funding Sources:
Funding from DOE under a cooperative agreement is for basic research in nuclear medicine, which may or may not be used for human subject research studies in a given fiscal year.
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: October 02, 1996
IRB Approval Number: 92-11-640-04A
Number of Human Subjects who participated in this project/protocol during
FY 1997 (10/1/96 - 9/30/97): 0
Type 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 labelled 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 (See UCLA-47-87ER60615 in FY96 database)
Principal Investigator:
Dr. Heinrich R. Schelbert
Project started in: 1993
Project Funding Information:
Project received funding in Fiscal Year 1997.
Project did not use human subjects in Fiscal Year 1997.
Explanation:
Study was inactive during this fiscal year
Funding Sources:
Funding from DOE under a cooperative agreement is for basic research in nuclear medicine, which may or may not be used for human subject research studies in a given fiscal year.
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: April 28, 1997
IRB Approval Number: 93-11-654-11
Number of Human Subjects who participated in this project/protocol during
FY 1997 (10/1/96 - 9/30/97): 0
Type of Human Subjects Involvement:
Calibration for PET scan
Internal administration of radioactive substances to human subjects.
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-95-036
Project Title:
Dopamine Transport and Storage Measured with [18F] Fluoro-L-m-Tyrosine
Principal Investigator:
Dr. Gary W. Small
Project started in: 1995
Project Funding Information:
Project received funding in Fiscal Year 1997.
Project did not use human subjects in Fiscal Year 1997.
Explanation:
Project was inactive in FY97; no human subjects were studied.
Funding Sources:
Funding from DOE under a cooperative agreement is for basic research in nuclear medicine, which may or may not be used for human subject research studies in a given fiscal year.
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: October 02, 1996
IRB Approval Number: 95-01-036-02
Number of Human Subjects who participated in this project/protocol during
FY 1997 (10/1/96 - 9/30/97): 0
Type of Human Subjects Involvement:
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 and thirty patient volunteers will be studied initially.
Risks will include the risk of having blood drawn, with potential side effects including momentary discomfort during the puncture, lightheadedness, faintness, soreness and discoloration of the area. Risks from the administration of L-DOPA produce some side effects in some patients including, symptoms involving movements of the muscles of the body and the eyes or a restless feeling, changes in heart rhythm in susceptible individuals, decreases in blood pressure, confusion and nausea. Should such side effects occur, the drug will be stopped immediately and the appropriate anti-arrhythmic drugs administered, if necessary. Arterial blood samples may be removed. Adverse reactions can occur in some individuals from the anesthetic agent, including shortness of breath, allergic reaction, low blood pressure and, extremely rarely, problems with heart rhythm or seizures. Also, arterial spasm can occur, making the hands cold and painful. Risks from the MRI include anxiety at being in a tight, enclosed space, and magnetism to certain metals.
No information that identifies the patient will be released without the patient'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
Project started in: 1995
Project Funding Information:
Project received funding in Fiscal Year 1997.
Project used human subjects in Fiscal Year 1997.
Funding Sources:
Funding from DOE under a cooperative agreement is for basic research in nuclear medicine, which may or may not be used for human subject research studies in a given fiscal year.
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: September 25, 1997
IRB Approval Number: 95-03-117-03
Number of Human Subjects who participated in this project/protocol during
FY 1997 (10/1/96 - 9/30/97): 33
Type of Human Subjects Involvement:
Calibration for PET scan
Internal administration of radioactive substances to human subjects.
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 (See UCLA-96-450 in FY96 database)
Principal Investigator:
Dr. Johannes Czernin
Project started in: 1995
Project Funding Information:
Project received funding in Fiscal Year 1997.
Project used human subjects in Fiscal Year 1997.
Funding Sources:
Funding from DOE under a cooperative agreement is for basic research in nuclear medicine, which may or may not be used for human subject research studies in a given fiscal year.
This grant provides salary support only to Dr. Czernin, the PI of this human subject study.
Total Funding: $15,000
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: March 25, 1997
IRB Approval Number: 95-10-450-02A
Number of Human Subjects who participated in this project/protocol during
FY 1997 (10/1/96 - 9/30/97): 42
Type of Human Subjects Involvement:
Calibration for PET scan
Internal administration of radioactive substances to human subjects.
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
Project started in: 1996
Project Funding Information:
Project received funding in Fiscal Year 1997.
Project used human subjects in Fiscal Year 1997.
Funding Sources:
Funding from DOE under a cooperative agreement is for basic research in nuclear medicine, which may or may not be used for human subject research studies in a given fiscal year.
Project does not involve use of multiple protocols/subprojects.
Protocol/Subproject Identifier: 0
IRB Review:
Type of Review: Full Board
Most Recent Approval: May 02, 1997
IRB Approval Number: 96-02-082-02
Number of Human Subjects who participated in this project/protocol during
FY 1997 (10/1/96 - 9/30/97): 7
Type 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 of 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. Johannes Czernin
Project started in: 1996
Project Funding Information:
Project received funding in Fiscal Year 1997.
Project did not use human subjects in Fiscal Year 1997.
Explanation:
Project was approved by IRB but no human subjects were studied.
Funding Sources:
Funding from DOE under a cooperative agreement is for basic research in nuclear medicine, which may or may not be used for human subject research studies in a given fiscal year.
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: June 12, 1997
IRB Approval Number: 95-09-426-02
Number of Human Subjects who participated in this project/protocol during
FY 1997 (10/1/96 - 9/30/97): 0
Type of Human Subjects Involvement:
Calibration for PET scan
Internal administration of radioactive substances to human subjects.
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-97-490
Project Title:
Whole Body PET scanning with Flouride-18 and FDG
Principal Investigator:
Dr. Carl K. Hoh
Project started in: 1997
Project Funding Information:
Project received funding in Fiscal Year 1997.
Project used human subjects in Fiscal Year 1997.
Funding Sources:
Funding from DOE under a cooperative agreement is for basic research in nuclear medicine, which may or may not be used for human subject research studies in a given fiscal year.
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: January 21, 1997
IRB Approval Number: 96-11-490-01
Number of Human Subjects who participated in this project/protocol during
FY 1997 (10/1/96 - 9/30/97): 13
Type of Human Subjects Involvement:
18F-bone scans have been shown to produce high resolution tomographic bone images with improved lesion detectability due to the higher lesion contrast from the tomographic technique. Fluorodeoxyglucose (FDG) PET imaging has been useful for detecting tumor lesions in patients with malignancy; however, it is sometimes difficult to accurately localize the lesion(s) anatomically. The combination of a 18F- PET bone scan and a FDG PET tissue scan may allow more accurate anatomical localization of a FDG lesion.
No more than 12 patients with tumor lesions will be studied. Subjects who are suspected of being pregnant will not be studied.
The basic procedure to be performed will involve the intravenous injection of a small amount of 18F- ion and FDG. The 18F- ion will be adsorbed by the bones in the body reflecting the relative rates of fluoride uptake in the bones, while the FDG will be taken up by the soft tissues reflecting glucose metabolism. Total acquisition time is approximately 1-2 hours.
The 18F- fluoride and FDG will be prepared in our laboratory with pharmaceutical grade materials and good pharmaceutical practice. The identity and chemical assay of the solution, as well as the freedom from radiochemical and radionuclide impurities, will be determined. Assay for total radioactivity will be by ionization chamber prior to use in humans.
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.