Mr. David McGraw
MS 90-1140
1 Cyclotron Road
Berkeley, CA 94720
Phone: 510-486-5551
Fax: 510-486-7488
E-mail: dcmcgraw@lbl.gov
Number of Human Subjects projects reported: 36
"Experimental Medicine Clinical"
Principal Investigator: Dr. Thomas F. Budinger, Lawrence Berkeley National Laboratory
Project started in: 1975
Funding for Human Subjects Research:
This project involves the use of multiple protocols/subprojects.
Number of protocols/subprojects associated with this project: 16
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Lawrence Berkeley National Laboratory
Most recent approval: 04/07/00
IRB approval number: 2000-4-62
Explanation of IRB approval:
Protocol discontinued by investigator in March, 2001.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Other: 04/07/00 to 03/15/01
Explanation:
Final period during which protocol was approved.
Type(s) of Human Subjects Involvement:
TITLE: Human Tumor Evaluation by Fluorodeoxyglucose and PET
OBJECTIVES
The objective of this study is the development and use of new technologies for the study of brain tumors. The focus is on the development of advanced emission tomography imaging modalities, as well as further development of magnetic resonance imaging techniques. This study hopes to lead in the development of effective brain tumor diagnosis and staging programs.
METHODOLOGY
Subjects with confirmed brain tumors are given radiotracer enhanced positron emission tomography (PET) scans before and 18 months after radiation therapy. As part of this procedure, patients are given both a venous and an arterial catheter for the administration of the radiotracer [fluorodeoxyglucose (FDG-18)]. Children receive a second venous catheter instead of an arterial catheter.
IONIZING RADIATION, RADIOACTIVE SUBSTANCES, OR CHEMICAL SUBSTANCES
Fluorine-18 Fluorodeoxyglucose (FDG-18) is used to enhance the PET scans.
INVOLVEMENT OF AND RISKS TO HUMAN SUBJECTS
PET scan risks include: venous catheter (bruising, faintness); arterial catheter (bruising, pain, faintness, development of a blot clot [1%]); radiation (equivalent to back x-ray).
CONFIDENTIALITY
The identities of the subjects are known, but any public report is by code numbers only. Results from PET and MRI are supplied to the patients' personal physicians. Subjects are reminded that the Food and Drug Administration may have access to their records and that research records are not immune to subpoena.
THIS PROTOCOL WAS DISCONTINUED IN MARCH 2001.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Lawrence Berkeley National Laboratory
Most recent approval: 10/12/00
IRB approval number: 2000-10-67
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 1
Reporting period for number of human subjects:
Year prior to last IRB approval date
Type(s) of Human Subjects Involvement:
TITLE: PET Study of Breast Cancer
OBJECTIVES
To evaluate the efficacy of the positron emission tomography (PET)-fluorodeoxyglucose (FDG-18) modality in detecting the presence and size of primary and metastatic breast cancer. The LBNL procedures are to be applied twice, once during the initial visit, then two to four months following this initial scan. The subject may benefit from the detection of the presence of metastasis. Society may benefit from an improved technique for the diagnosis and management of future breast cancer patients.
METHODOLOGY
A catheter will be placed in a vein in one arm to inject the radiotracer. Subjects are then positioned in the PET scanner, where the technician provides blankets and padding in order to make them as comfortable as possible. Subjects may not move during the scan, which may last as long as 120 minutes. A second scan will be performed two to four months following the initial scan to evaluate progression of the disease for subjects off therapy or therapeutic response for subjects who are receiving therapy.
IONIZING RADIATION, RADIOACTIVE SUBSTANCES, OR CHEMICAL SUBSTANCES
Fluorine-18 Fluorodeoxyglucose (FDG-18)
INVOLVEMENT OF AND RISKS TO HUMAN SUBJECTS
PET scan risk includes: venous catheter (bruising, faintness); radiation (equivalent to kidney x-ray).
CONFIDENTIALITY
The identities of the subjects are known, but any public report is by code numbers only. Results from PET and/or MRI are supplied to the patients' personal physicians. Subjects are reminded that the Food and Drug Administration may have access to their records and that research records are not immune to subpoena.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Lawrence Berkeley National Laboratory
Most recent approval: 10/12/01
IRB approval number: 2001-10-52
Explanation of IRB approval:
Protocol was under review at the end of the fiscal year and was only renewed just after the fiscal year began.
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:
OBJECTIVES
To evaluate the efficacy of the positron emission tomography (PET)-fluorodeoxyglucose (FDG-18) modality in detecting the viability of the heart muscle. The current trial is aimed at determining which of the patients with a negative diagnosis by a thallium perfusion study have a positive diagnosis for reversible disease by FDG. The benefit of this study to the subject and future individuals with damaged heart muscle is reversibility.
METHODOLOGY
Subjects are offered water before their study begins. A catheter will be placed in a vein in one arm to inject the radiotracer. After a half-hour uptake phase, subjects are asked to empty their bladder to keep the radiation exposure to the bladder as low as possible. Subjects are then positioned in the PET scanner, where the technician provides blankets and padding in order to make them as comfortable as possible. Subjects may not move during the scan, which may last as long as 120 minutes.
IONIZING RADIATION, RADIOACTIVE SUBSTANCES, OR CHEMICAL SUBSTANCES
Fluorine-18 Fluorodeoxyglucose.
INVOLVEMENT OF AND RISKS TO HUMAN SUBJECTS
PET scan risks include: venous catheter (bruising, faintness); radiation (equivalent to a back x-ray).
CONFIDENTIALITY
The identities of the subjects are known, but any public report is by code numbers only. Results from PET and/or MRI are supplied to the patients' personal physicians. Subjects are reminded that the Food and Drug Administration may have access to their records and that research records are not immune to subpoena.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Lawrence Berkeley National Laboratory
Most recent approval: 08/25/00
IRB approval number: 2000-8-118
Explanation of IRB approval:
Renewal of this protocol is pending submission of a major modification by the researcher.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Other: 08/25/00 to 08/24/01
Explanation:
Period between the last IRB review and approval and expiration of the protocol.
Type(s) of Human Subjects Involvement:
TITLE: Coronary Artery Disease Evaluation by Quantitative Perfusion Studies Using 13NH3 and PET
OBJECTIVES
The purpose of this project is to develop noninvasive, rapid, and economical methods for the evaluation of cardiac ischemia. This protocol will evaluate the clinical utility of quantitative heart perfusion data obtained with the radiotracer 13-nitrogen ammonia (13NH3) and Positron Emission Tomography (PET). The PET scan may provide information that could benefit the patient in his/her overall therapy management, but such a benefit is not assured. Society would benefit from improved and more economical diagnostic tests.
METHODOLOGY
A catheter will be placed in a vein in one arm to inject the radiotracers and to collect blood samples to verify the rate at which the radiotracer is cleared from the blood. A blood glucose test will be performed, and patients with blood sugars less that 120 mg% will receive oral glucose loading. After positioning the subject in the PET scanner, a transmission scan without radiotracer will be done to allow corrections of the emission data. Next the first 35 mCi dose of 13NH3 is injected and a resting PET scan is taken. Between 30 and 40 minutes after the initial tracer injection, dipyridamole will be infused intravenously. The second 13NH3 injection is given about 4 minutes after the perfusion is completed and the final PET scan begins shortly thereafter. Subjects may not move during the scans. The total procedure should take about 120 minutes.
RADIATION/CHEMICAL SUBSTANCES
13-nitrogen ammonia; dipyridamole
INVOLVEMENT OF HUMAN SUBJECTS
Risks include: venous catheter (bruising, faintness); radiation (equivalent to kidney x-ray); and the routine risks associated with any clinical use of dipyridamole (occasional severe chest pain, severe hypotension, respiratory distress, and vomiting or nausea; rarely, symptoms of myocardial ischemia requiring the use of aminophylline to reverse the effect; very rarely, heart attack or death).
CONFIDENTIALITY
The identities of the subjects are known, but any public report is by code numbers only. Results from PET scans are supplied to the patients' personal physicians. Subjects are reminded that the Food and Drug Administration may have access to their records and that research records are not immune to subpoena.
RENEWAL OF THIS PROTOCOL IS PENDING A MAJOR REVISION BY THE RESEARCHER. NO SUBJECTS WILL BE STUDIED UNDER THE PROTOCOL UNTIL IT IS AGAIN FULLY APPROVED BY THE INSTITUTIONAL REVIEW BOARD.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Lawrence Berkeley National Laboratory
Most recent approval: 08/25/00
IRB approval number: 2000-8-124
Explanation of IRB approval:
Renewal of this protocol is pending submission of a major revision by the researcher.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Other: 08/25/00 to 08/25/01
Explanation:
Period between last review and approval by the IRB and expiration date of the protocol.
Type(s) of Human Subjects Involvement:
TITLE: Coronary Artery Disease Evaluation by 13-Ammonia Perfusion and Deoxyglucose Uptake Measured by PET and Three-Dimensional MR Myocardial Tagging
OBJECTIVES
The purpose of this project is to develop noninvasive, rapid, and economical methods for the evaluation of myocardial perfusion and metabolism. This protocol will compare magnetic resonance imaging (MRI) strain data from rest and low dose dobutamine stress conditions to PET 13-ammonia/
18F-fluorodeoxyglucose (FDG) studies to determine which is the superior technique.
The PET scan may provide information that could benefit the patient in his/her overall therapy management, but such a benefit is not assured. Society would benefit from improved and more economical diagnostic tests.
METHODOLOGY
MRI: The standard medical procedure for myocardial tagging image will be used. Subjects will discontinue beta-blocker medications 48 hours before the procedure (with the permission of their personal physician/cardiologist). A venous catheter will be placed and heart rate and blood pressure monitors attached. After a resting MRI, dobutamine will be administered as a cardiac stressor. Drugs to counteract the effect of the dobutamine, if needed, will be on hand.
PET: Patients will fast the night before scanning. Subjects are offered water before their study begins. A catheter will be placed in a vein in one arm to inject the radiotracers and to collect blood samples to verify the rate at which the radiotracer is cleared from the blood. First the 13-ammonia scan is performed. Subjects are then allowed to void if necessary. Then a transmission scan without radiotracer is performed to allow corrections of the emission data. Lastly, the 18-FDG study is done. Subjects may not move during the scans. The total procedure should take about 120 minutes.
RADIATION/CHEMICAL SUBSTANCES
MRI: dobutamine
PET: Fluorine-18 fluorodeoxyglucose; nitrogen-13 ammonia
INVOLVEMENT OF HUMAN SUBJECTS
Each of the subjects will have two MRI studies but most subjects will have only a single 13-ammonia vs. 18-FDG uptake PET study.
MRI risks include: venous catheter (bruising, faintness); the discomfort of lying still in an enclosed space for a long period of time; the rare chance of an allergic reaction to dobutamine; the possibility of discomfort associated with discontinuing medication 48 hours prior to the study; and the rare possibility (as with any stress test) of arrhythmia, heart attack, or death.
PET scan risk includes: venous catheter (bruising, faintness); radiation (equivalent to kidney x-ray).
CONFIDENTIALITY
The identities of the subjects are known, but any public report is by code numbers only. Results from PET and or MRI are supplied to the patients' personal physicians. Subjects are reminded that the Food and Drug Administration may have access to their records and that research records are not immune to subpoena.
RENEWAL OF THIS PROTOCOL IS PENDING A MAJOR REVISION BY THE RESEARCHER. NO SUBJECTS WILL BE STUDIED UNDER THE PROTOCOL UNTIL IT IS AGAIN FULLY APPROVED BY THE INSTITUTIONAL REVIEW BOARD.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Lawrence Berkeley National Laboratory
Most recent approval: 08/25/00
IRB approval number: 2000-8-117
Explanation of IRB approval:
Renewal of this protocol is still pending; the researcher will be submitting a major revision.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Other: 08/25/00 to 08/25/01
Explanation:
Period between the last IRB review and approval and expiration of the protocol.
Type(s) of Human Subjects Involvement:
OBJECTIVES
The objectives of this study are to utilize magnetic resonance imaging (MRI) and positron emission tomography (PET) on patients with Alzheimer's disease, Parkinson's disease, and multi-infarct dementia to understand the longitudinal effects of these conditions on cerebral metabolism, to develop a new serotonin-based radiotracer which will provide a measure of the presynaptic degeneration in these cases and to correlate the presynaptic degeneration with behavioral changes. The new tracer will also be used to investigate serotonergic degeneration in these diseases. Societal benefits may include a greater understanding of dementing illnesses.
METHODOLOGY
Subjects are accompanied by an adult family member or guardian to assure an appropriate consent process. Subjects are offered water before their study begins. A catheter will be placed in a vein in one arm and another will be placed in an artery or vein of the hand on the other arm. The venous catheter will be used to inject the radiotracer and the arterial (or other venous) catheter will be used to collect blood samples to verify the rate at which the radiotracer is cleared from the blood. After a half-hour uptake phase, subjects are asked to empty their bladder to keep the radiation exposure to the bladder as low as possible. Subjects then watch a video display terminal on which words are presented. A delayed word presentation is used to determine the duration of subjects' memory. Subjects are then positioned in the PET scanner, where the technician provides blankets and padding in order to make them as comfortable as possible. Subjects may not move during the scan, which may last 60 to 90 minutes. Subsequently, the subjects may be placed in a MRI scanner for 2 scans totaling approximately 30 minutes.
IONIZING RADIATION, RADIOACTIVE SUBSTANCES, OR CHEMICAL SUBSTANCES
Fluorine-18 Fluorodeoxyglucose
INVOLVEMENT OF AND RISKS TO HUMAN SUBJECTS
PET scan risk includes: venous catheter (bruising, faintness); arterial catheter (bruising, pain, faintness); radiation (equivalent to back x-ray). If an arterial catheter is to be placed, lidocaine is used to provide local anesthesia before placing the catheter.
MRI scan risk includes discomfort associated with lying still in an enclosed space.
CONFIDENTIALITY
The identities of the subjects are known, but any public report is by code numbers only. Results from PET and/or MRI are supplied to the patients' personal physicians. Subjects are reminded that the Food and Drug Administration may have access to their records and that research records are not immune to subpoena. In patients whose cognition is or may be impaired, the consent of the responsible next of kin or conservator as well as the assent of the patient will be sought.
NOTE: The number of subjects participating under this protocol is reported under "Alzheimer's Disease as a Systemic Disorder" (LBNL-84-001-H03). Additional subjects were not studied under this project, therefore, the number of subjects reported here is zero to prevent counting the same subjects twice.
RENEWAL OF THIS PROTOCOL IS PENDING A MAJOR REVISION BY THE RESEARCHER. NO SUBJECTS WILL BE STUDIED UNDER THE PROTOCOL UNTIL IT IS AGAIN FULLY APPROVED BY THE INSTITUTIONAL REVIEW BOARD.
Institutional Review Board (IRB) Review:
Type of Review: Expedited
Approving Institution: Lawrence Berkeley National Laboratory
Most recent approval: 04/14/01
IRB approval number: 2001-3-51
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:
TITLE: Cardiovascular Relationships in Alzheimer's Disease --Determination of Peripheral Vascular Reactivity
OBJECTIVES
The goal of this study is to demonstrate the presence or absence of strong correlations between Alzheimer's disease (AD) and peripheral cardiovascular disease. Societal benefits may include a greater understanding of dementing illnesses.
METHODOLOGY
An equal number of control subjects and AD patients will be recruited. Patient subjects are accompanied by an adult family member or guardian to assure an appropriate consent process. AD patients will have been previously evaluated by their treating clinic and these results will be made available to the researchers.
On the day of the study, a small sample of venous blood will be drawn for lipoprotein analysis in order to correlate LDL levels, reactivity and subject illness. Vascular reactivity to the tightening and releasing of a blood pressure cuff will then be non-invasively measured using a Food and Drug Administration approved Doppler flow system.
IONIZING RADIATION, RADIOACTIVE SUBSTANCES, OR CHEMICAL SUBSTANCES
None
INVOLVEMENT OF AND RISKS TO HUMAN SUBJECTS
Study risks include: venous catheter (bruising, faintness), discomfort due to the squeezing of the blood pressure cuff.
CONFIDENTIALITY
The identities of the subjects are known, but any public report is by code numbers only. The results from the venous blood analysis are supplied to the patients' personal physicians upon request. Subjects are reminded that the Food and Drug Administration may have access to their records and that research records are not immune to subpoena. In patients whose cognition is or may be impaired, the consent of the responsible next of kin or conservator as well as the assent of the patient will be sought.
NOTE: The number of subjects participating under this protocol is reported under "Alzheimer's Disease as a Systemic Disorder" (LBNL-84-001-H03).
Institutional Review Board (IRB) Review:
Type of Review: Expedited
Approving Institution: Lawrence Berkeley National Laboratory
Most recent approval: 10/09/01
IRB approval number: 2001-10-75
Explanation of IRB approval:
Approval is based on review of another IRB which did occur during FY 2001.
Additional IRB approvals from other institutions:
Type of Review: Full Board
Approving Institution: University of California at San Francisco
Most recent approval: 08/02/01
IRB approval number: H5637-15422-04
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Year prior to last IRB approval date
Type(s) of Human Subjects Involvement:
TITLE: PET Transmission Studies
OBJECTIVE
The goal of this project is to produce better quality Positron Emission Tomography (PET) images with higher resolution. The researchers will examine how PET technology and analysis algorithms can compensate for the slight movements made by the chest during normal breathing. Subjects will receive no direct benefit, but society may benefit from improved PET diagnostic techniques.
METHODOLOGY
Subjects will receive a single PET scan of 1 - 2 hours without catheterization or radiotracer.
INVOLVEMENT OF AND RISKS TO HUMAN SUBJECTS
PET scan risk includes: the discomfort of lying still for a prolonged period; radiation (equivalent to less than 1/20th of a back x-ray). Note that no radiotracer is given.
CONFIDENTIALITY
The identities of the subjects are known, but any public report is by code numbers only. Subjects are reminded that research records are not immune to subpoena.
IN 1998, THE PERFORMANCE SITE OF THESE STUDIES CHANGED TO THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Lawrence Berkeley National Laboratory
Most recent approval: 08/25/00
IRB approval number: 2000-8-122
Explanation of IRB approval:
Renewal of this protocol is still pending; the researcher will be submitting a major revision.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Other: 08/25/00 to 08/24/01
Explanation:
Period between the last IRB review and approval and expiration of the protocol.
Type(s) of Human Subjects Involvement:
TITLE: Head and Neck Tumor Evaluation by Fluorodeoxyglucose and PET
OBJECTIVES
To evaluate the efficacy of the positron emission tomography (PET)-fluorodeoxyglucose (FDG-18) modality in detecting the presence and size of primary and metastatic cancer involving the head and neck. The subject may benefit from pre- and post-therapy PET scans in diagnosing and monitoring the status of his/her illness. Society may benefit from an improved technique for the diagnosis, prognosis and management of future patients with head and neck tumors.
METHODOLOGY
Subjects are offered water before their study begins. A catheter will be placed in a vein in one arm to inject the radiotracer and to collect blood samples to verify the rate at which the radiotracer is cleared from the blood. After a half-hour uptake phase, subjects are asked to empty their bladder to keep the radiation exposure to the bladder as low as possible. Subjects are then positioned in the PET scanner, where the technician provides blankets and padding in order to make them as comfortable as possible. Subjects may not move during the scan, which may last as long as 120 minutes.
The LBNL procedures are to be applied before and after treatment. A third PET study may be performed if the first or second study suffers a correctable problem (e.g., instrument failure) and the study is deemed important to the patient, or if a third study is indicated to evaluate the long-term outcome of therapy.
IONIZING RADIATION, RADIOACTIVE SUBSTANCES, OR CHEMICAL SUBSTANCES
Fluorine-18 Fluorodeoxyglucose (FDG-18)
INVOLVEMENT OF AND RISKS TO HUMAN SUBJECTS
PET scan risk includes: venous catheter (bruising, faintness); radiation (equivalent to back x-ray).
CONFIDENTIALITY
The identities of the subjects are known, but any public report is by code numbers only. Results from PET scan(s) are supplied to the patients' personal physicians. Subjects are reminded that the Food and Drug Administration may have access to their records and that research records are not immune to subpoena.
RENEWAL OF THIS PROTOCOL IS PENDING A MAJOR REVISION BY THE RESEARCHER. NO SUBJECTS WILL BE STUDIED UNDER THE PROTOCOL UNTIL IT IS AGAIN FULLY APPROVED BY THE INSTITUTIONAL REVIEW BOARD.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Lawrence Berkeley National Laboratory
Most recent approval: 04/06/01
IRB approval number: 2001-4-92
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:
TITLE: Evaluation of Vascular Reactivity in Alzheimer's Disease via Iontophoresis of Vasoactive Compounds
OBJECTIVES
The goal of this study is to continue to examine the presence or absence of strong correlations between Alzheimer's disease (AD) and peripheral cardiovascular disease. Societal benefits may include a greater understanding of dementing illnesses.
METHODOLOGY
An equal number of control subjects and AD patients will be recruited. Patient subjects are accompanied by an adult family member or guardian to assure an appropriate consent process. AD patients will have been previously evaluated by their treating clinic and these results will be made available to the researchers.
On the day of the study, subjects will be screened for factors such as the use of aspirin. A small sample of venous blood will be drawn for lipoprotein analysis in order to correlate LDL levels, reactivity and subject illness. A picture of the blood vessels in the hand will be taken using a laser scanner. The laser is similar in intensity to a laser pointer and is not damaging to the skin.
The skin will be cleaned using isopropyl alcohol. Small amounts of up to five vasodilators and/or constrictors will be dabbed onto the subject's skin. A one inch square electrode will be placed over the applied chemical, and a tiny electric current applied to cause the chemical to move into localized areas the skin and underlying capillaries. Changes in the circulation will then be non-invasively measured using the same non-invasive laser scanner described above.
IONIZING RADIATION, RADIOACTIVE SUBSTANCES, OR CHEMICAL SUBSTANCES
The vasodilators and/or constrictors which may be applied to localized areas of the skin of the arm are: sildenafil citrate; nitro-L-arginine methy ester; nitroprusside; methacholine; acetylcholine. None of the applications will result in a significant or even measurable systemic dose.
INVOLVEMENT OF AND RISKS TO HUMAN SUBJECTS
Study risks include: venous catheter (bruising, faintness); minor skin irritation or allergic reaction from the chemicals applied to the skin; a slight, transient tingling feeling from the iontophoresis electrode.
CONFIDENTIALITY
The identities of the subjects are known, but any public report is by code numbers only. The results from the venous blood analysis are supplied to the patients' personal physicians upon request. Subjects are reminded that research records are not immune to subpoena. In patients whose cognition is or may be impaired, the consent of the responsible next of kin or conservator as well as the assent of the patient will be sought.
NOTE: The number of subjects participating under this protocol is reported under "Alzheimer's Disease as a Systemic Disorder" (LBNL-84-001-H03). Additional subjects were not studied under this project, therefore, the number of subjects reported here is zero to prevent counting the same subjects twice.
Institutional Review Board (IRB) Review:
Type of Review: Expedited
Approving Institution: Lawrence Berkeley National Laboratory
Most recent approval: 06/22/01
IRB approval number: 2001-6-149
Additional IRB approvals from other institutions:
Type of Review: Full Board
Approving Institution: University of California at San Francisco
Most recent approval: 04/19/01
IRB approval number: H5637-14948-04
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Year prior to last IRB approval date
Type(s) of Human Subjects Involvement:
TITLE: Coronary Artery Disease Evaluation by Quantitative Perfusion Studies Using Rest/Stress 62-Cu PTSM and Positron Emission Tomography (PET) vs. Rest/Stress 201 T1 or 99mTc - Sestamibi Single Photon Emission Computed Tomography (SPECT)
OBJECTIVES
The purpose of this project is to develop noninvasive, rapid, and economical methods for the evaluation of cardiac ischemia. This protocol will compare the clinical utility of quantitative heart perfusion data obtained with the radiotracer 62-copper pyruvaldehyde Bis (N(4)-methyl) thiosemicarbazone (62-Cu PTSM) and PET scanning to SPECT scans done with Food and Drug Administration approved perfusion tracers.
The PET scan may provide information that could benefit the patient in his/her overall therapy management, but such a benefit is not assured. Society would benefit from improved and more economical diagnostic tests.
METHODOLOGY
Subjects with suspected stable ischemic coronary artery disease who either have undergone or are scheduled to undergo coronary angiography and a SPECT myocardial perfusion study will be recruited for this protocol. Neither the angiography nor the SPECT scan will be performed as part of this study.
For the PET scan, a catheter will be placed in a vein in one arm to inject the radiotracers and to collect blood samples to verify the rate at which the radiotracer is cleared from the blood. After positioning the subject in the PET scanner, a transmission scan without radiotracer will be done to allow corrections of the emission data. Next the first 30 mCi dose of 62-Cu PTSM is injected and a resting PET scan is taken. Between 40 and 50 minutes after the initial tracer injection, hypotension will be induced by adenosine or dipyridamole injection or by cold pressor stimulation (immersion of a hand in ice water). The second 62-Cu PTSM injection is given about 4 minutes after the infusion of adenosine or dipyridamole (or 30 seconds after cold pressor stimulation) is completed and the final PET scan begins shortly thereafter. Subjects may not move during the scans. The effect of dipyridamole will be reversed by the use of aminophylline; the effect of cold pressor stimulation by the use of nitroglycerine if needed. The total procedure should take about 120 minutes.
RADIATION/CHEMICAL SUBSTANCES
62-Cu PTSM; adenosine or dipyridamole and aminophylline or possibly nitroglycerine
INVOLVEMENT OF HUMAN SUBJECTS
Risks include: venous catheter (bruising, faintness); radiation (equivalent to kidney x-ray); the routine risks associated with any clinical use of adenosine, dipyridamole or cold pressor stimulation (occasional severe chest pain, severe hypotension, respiratory distress, and vomiting or nausea; rarely, symptoms of myocardial ischemia requiring the use of aminophylline to reverse the effect; very rarely, heart attack or death), and the discomfort associated with lying still for an extended period of time.
Most subjects will receive only one PET scan. Up to five subjects will receive a second 62-Cu PTSM PET study.
CONFIDENTIALITY
The identities of the subjects are known, but any public report is by code numbers only. Results from PET scans are supplied to the patients' personal physicians. Subjects are reminded that the Food and Drug Administration may have access to their records and that research records are not immune to subpoena.
THE SITE AT WHICH THESE PET STUDIES TAKE PLACE CHANGED TO THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, IN MAY, 1999.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Lawrence Berkeley National Laboratory
Most recent approval: 10/06/00
IRB approval number: 2000-10-56
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Other: 10/06/00 to 08/30/01
Explanation:
Final period during which protocol was approved.
Type(s) of Human Subjects Involvement:
TITLE: Skeletal Muscle Metabolism in Alzheimer's Disease
OBJECTIVES
Alzheimer's disease (AD) is known to be associated with change in cerebral glucose metabolism, and it has been suggested that AD is also associated with changes in muscular glucose utilization. The goal of this study is to quantify skeletal muscle glucose metabolism in subjects with Alzheimer's disease.
METHODOLOGY
An equal number of control subjects and AD patients will be recruited. Patient subjects are accompanied by an adult family member or guardian to assure an appropriate consent process. AD patients will have been previously evaluated by their treating clinic and these results will be made available to the researchers.
On the day of the study, subjects will fast for about two hours. They will then be given a light meal. A detailed exercise history for the week prior to the study will be taken. A small sample of venous blood will be drawn for insulin assay; blood glucose may be adjusted using glucola.
Subjects will lie on their stomachs with their legs through the ring of the PET scanner. The subject will exercise by repeatedly depressing a foot pedal for at least 15 minutes. The radiotracer F-18-fluorodeoxyglucose will be administered about 3 minutes into the exercise session. After the leg exercise and scan, subjects will urinate to reduce the dose to the bladder and then repositioned in the PET scanner for a brain scan. No additional radiotracer will be given.
Vascular reactivity to the tightening and releasing of a blood pressure cuff will also be non-invasively measured using a Food and Drug Administration approved Doppler flow system.
IONIZING RADIATION, RADIOACTIVE SUBSTANCES, OR CHEMICAL SUBSTANCES
Fluorine-18 Fluorodeoxyglucose
INVOLVEMENT OF AND RISKS TO HUMAN SUBJECTS
PET scan risk includes: venous catheter (bruising, faintness) and radiation (equivalent to back x-ray).
Other risks include muscle fatigue or cramping from depressing the pedal and discomfort due to the squeezing of the blood pressure cuff.
CONFIDENTIALITY
The identities of the subjects are known, but any public report is by code numbers only. The results from the venous blood analysis are supplied to the patients' personal physicians upon request. Subjects are reminded that the Food and Drug Administration may have access to their records and that research records are not immune to subpoena. In patients whose cognition is or may be impaired, the consent of the responsible next of kin or conservator as well as the assent of the patient will be sought.
NOTE: The number of subjects participating under this protocol is reported under "Alzheimer's Disease as a Systemic Disorder" (LBNL-84-001-H03). Additional subjects were not studied under this project, therefore, the number of subjects reported here is zero to prevent counting the same subjects twice.
THIS PROTOCOL WAS DISCONTINUED IN AUGUST 2001.
Institutional Review Board (IRB) Review:
Type of Review: Expedited
Approving Institution: Lawrence Berkeley National Laboratory
Most recent approval: 05/24/01
IRB approval number: 2001-1-36
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Other: 05/24/01 to 09/30/01
Explanation:
Initial period of approval falling within fiscal year.
Type(s) of Human Subjects Involvement:
TITLE: Ultrasound Assessment of the Effect of a Fatty Meal on Vascular and Hemodynamic Properties
OBJECTIVES
The objective of the study is to measure the hemodynamic and oxidative effects of a fatty meal on endothelial function and blood flow. Blood flow and arterial wall motion will be measured with an ultrasound device before and after meals with varying amounts of fat.
METHODOLOGY
Ten male and ten female subjects will be recruited by posting advertisements in local newspapers. Subjects with heart disease will be excluded. Each subject will be examined on nine separate occasions, before and after consuming three different meals (high fat high in saturated fat, high fat low in saturated fat, and low fat). The blood flow determination will be made with an experimental ultrasound device.
On the day of each study, subjects will be asked to fast. Upon arrival, their blood pressure and an initial sample of blood (1 tablespoon) will be taken. The blood will be analyzed for lipids, fatty acids, insulin and glucose levels, and blood viscosity. A hand-held ultrasound device will be put on the wrist, upper arm, or the bottom of the neck to take blood flow measurements.
Subjects will then consume a prepared meal of approximately one cup in volume. Additional blood samples will be drawn one and two hours post prandial, followed by an ultrasound assessment.
IONIZING RADIATION, RADIOACTIVE SUBSTANCES, OR CHEMICAL SUBSTANCES
The meals will be formulated under the direction of a nutritional scientist.
INVOLVEMENT OF AND RISKS TO HUMAN SUBJECTS
Study risks include: the risks common to a routine blood draw (bruising, faintness, and the slight chance of infection).
The Institutional Review Board found the ultrasound device to qualify for a non-significant risk Investigational Device Exemption.
PRIVACY/CONFIDENTIALITY/CONSENT
The identities of the subjects are known, but any public report is by code numbers only. The results from the venous blood analysis are supplied to the subjects upon request. Subjects are reminded that research records are not immune to subpoena, and are subject to review by the Food and Drug Administration.
Subjects will be paid $20 per visit for a total of nine studies ($180). If all nine studies are completed, a $20 bonus will be paid.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Lawrence Berkeley National Laboratory
Most recent approval: 01/12/01
IRB approval number: 2001-1-37
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 1
Reporting period for number of human subjects:
Other: 01/12/01 to 09/30/01
Explanation:
Initial period of approval falling within fiscal year.
Type(s) of Human Subjects Involvement:
TITLE: Evaluation of a New Instrument for the Assessment of Vascular Function
OBJECTIVES
The purpose of this study is to compare how well two different devices measure blood flow in the arteries of the arm. The goal is to produce a small, low cost device that could be used as part of a routine medical check-up to evaluate arterial health.
METHODOLOGY
Up to thirty male and female subjects will be recruited by posting advertisements in local newspapers. Subjects with heart disease, vascular conditions, clotting disorders, hypertension, or a recent venipuncture will be excluded. Each subject will be examined with both the relaxoscope (Device A, the test device) and B-mode/M-mode procedure (Device B, the current standard).
On the day of the study, each subject will receive a brief medical screening. The first 15 subjects will be tested with Device B first, and the second 15 with Device A first. After completion of the first test, subjects will wait about an hour and then be tested with the second device.
Device A procedure: The subject's arm will be positioned in a frame. An artificial pulse will be created by using a mechanical device to gently tap the arm throughout the procedure. A blood pressure cuff will be applied to the forearm of a subject and tightened to 200 - 220 mmHg (slightly tighter than used for normal blood pressure measurements) for 4-6 minutes. The sound of the artificial pulse will be recorded before, during, and for ten minutes after the blood pressure cuff is released using a Doppler stethoscope.
Device B procedure (the current standard): The subject's arm will be positioned in a different frame. EKG electrodes will be attached. A blood pressure cuff will be applied to the forearm of a subject and tightened to 200 - 220 mmHg (slightly tighter than used for normal blood pressure measurements) for about 4 minutes. Variation of the arterial diameter will be measured before, during and after release of the blood pressure cuff.
IONIZING RADIATION, RADIOACTIVE SUBSTANCES, OR CHEMICAL SUBSTANCES
None.
INVOLVEMENT OF AND RISKS TO HUMAN SUBJECTS
Study risks include:
Device A --Discomfort and the possibility of bruising from the blood pressure cuff; possibility of minor bruising from the tapping device or the frame.
Device B --Discomfort and the possibility of bruising from the blood pressure cuff and minor irritation from the electrode paste.
PRIVACY/CONFIDENTIALITY/CONSENT
The identities of the subjects are known, but any public report is by code numbers only. The results of the tests are discussed with the subjects. Subjects are reminded that research records are not immune to subpoena, and are subject to review by the Food and Drug Administration.
Because of the discomfort associated with wearing a blood pressure cuff tightened over 2000 mmHg for 4 to 6 minutes, subjects are specifically reminded that they can ask to have the cuff removed at any time.
Subjects will be paid $30 for completing the study.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Lawrence Berkeley National Laboratory
Most recent approval: 01/12/01
IRB approval number: 2001-1-35
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 4
Reporting period for number of human subjects:
Other: 01/12/01 to 09/30/01
Explanation:
Initial period of approval falling within protocol year.
Type(s) of Human Subjects Involvement:
TITLE: PET Study of Breast Cancer
OBJECTIVES
To evaluate the biokinetics of C-11 choline with a view towards its usefulness as a radiotracer for the identification of breast cancer. Choline is expected to be preferentially picked up by the tumor because of a known increase in choline kinase in malignant cells as compared to normal tissue.
METHODOLOGY
Up to thirty subjects with breast cancer confirmed through other diagnostic procedures will be recruited through contact with primary care physicians. Results from this scan will be correlated with other imaging modalities (magnetic resonance imaging, ultrasound, etc.) that are given to the subject as part of their clinical care.
Prior to the scan, a short medical history of the current disease and an accounting of food consumption during the prior 48 hours will be taken.
A catheter will be placed in a vein in one arm to inject the radiotracer. Subjects are then positioned in the PET scanner, where the technician provides blankets and padding in order to make them as comfortable as possible. Subjects may not move during the scan, which may last as long as 120 minutes. A second scan will be performed two to twelve months following the initial scan to evaluate changes in biokinetics associated with the subject's status and to determine if the kinetics of tumor uptake corresponds to that expected from other measures of cancer progression or regression.
IONIZING RADIATION, RADIOACTIVE SUBSTANCES, OR CHEMICAL SUBSTANCES
Carbon-11 Choline. This is a Radioactive Drug Research Committee monitored protocol.
INVOLVEMENT OF AND RISKS TO HUMAN SUBJECTS
PET scan risk includes: venous catheter (bruising, faintness); radiation (equivalent to kidney x-ray).
CONFIDENTIALITY
The identities of the subjects are known, but any public report is by code numbers only. Results from PET are supplied to the patients' personal physicians. Subjects are reminded that the Food and Drug Administration may have access to their records and that research records are not immune to subpoena.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Lawrence Berkeley National Laboratory
Most recent approval: 01/12/01
IRB approval number: 2001-1-34
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Other: 01/12/01 to 09/30/01
Explanation:
Initial period of approval falling within fiscal year.
Type(s) of Human Subjects Involvement:
TITLE: PET Study of Prostate Cancer
OBJECTIVES
To evaluate the biokinetics of Carbon-11 choline with a view towards its usefulness as a radiotracer for the identification of prostate cancer and its metastasis. Choline is expected to be preferentially picked up by the tumor because of a known increase in choline kinase in malignant cells as compared to normal tissue. Choline may also be a better candidate for prostate imaging as it is not expected to collect in the bladder.
METHODOLOGY
Up to thirty subjects with prostate cancer confirmed through other diagnostic procedures will be recruited through contact with primary care physicians. Results from this scan will be correlated with other imaging modalities (magnetic resonance imaging, ultrasound, etc.) that are given to the subject as part of their clinical care.
Prior to the scan, a short medical history of the current disease and an accounting of food consumption during the prior 48 hours will be taken.
A catheter will be placed in a vein in one arm to inject the radiotracer. Subjects are then positioned in the PET scanner, where the technician provides blankets and padding in order to make them as comfortable as possible. Subjects may not move during the scan, which may last as long as 120 minutes. A second scan will be performed two to twelve months following the initial scan to evaluate changes in biokinetics associated with the subject's status and to determine if the kinetics of tumor uptake corresponds to that expected from other measures of cancer progression or regression.
IONIZING RADIATION, RADIOACTIVE SUBSTANCES, OR CHEMICAL SUBSTANCES
Carbon-11 Choline. This is a Radioactive Drug Research Committee monitored protocol.
INVOLVEMENT OF AND RISKS TO HUMAN SUBJECTS
PET scan risk includes: venous catheter (bruising, faintness); radiation (equivalent to kidney x-ray).
CONFIDENTIALITY
The identities of the subjects are known, but any public report is by code numbers only. Results from PET are supplied to the patients' personal physicians. Subjects are reminded that the Food and Drug Administration may have access to their records and that research records are not immune to subpoena.
"Studies of Lipoproteins and Lipid Protein Interactions"
Principal Investigator: Dr. Edward Rubin, Lawrence Berkeley National Laboratory
Project started in: 1977
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review: Expedited
Approving Institution: Lawrence Berkeley National Laboratory
Most recent approval: 04/19/01
IRB approval number: 2001-4-94
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:
OBJECTIVES
Interdisciplinary training program in cellular, molecular, and biophysical aspects of lipid and lipoprotein metabolism and the process of atherogenesis.
METHODOLOGY
Trainees participate in research carried out under other approved protocols. In the past, trainees have utilized blood samples drawn under the protocol LBNL-79-106-H02 (Krauss, Ronald: "Metabolic & Genetic Origins of Lipoprotein Subclasses"). No other involvement with human subjects has been reported.
INVOLVEMENT OF AND RISKS TO HUMAN SUBJECTS
Human subjects involvement in the last few years has been limited to the use of surplus blood collected for another project. No additional risks to subjects are incurred as a result of this grant.
CONFIDENTIALITY
Confidentiality provisions are the same as those of the source protocol. Only samples collected under consent processes that inform subjects that their samples may be used in other research projects may be used by fellows under this training grant.
NO POST-DOCTORAL TRAINEES PARTICIPATED IN HUMAN SUBJECTS RESEARCH IN FISCAL YEAR 2001.
"Lipoproteins and Atherogenesis in Transgenic Animals"
Principal Investigator: Dr. Ronald M. Krauss, Lawrence Berkeley National Laboratory
Project started in: 1979
Funding for Human Subjects Research:
This project involves the use of multiple protocols/subprojects.
Number of protocols/subprojects associated with this project: 3
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Lawrence Berkeley National Laboratory
Most recent approval: 02/09/01
IRB approval number: 2001-2-23
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:
TITLE: Blood Donations for Family Studies
OBJECTIVES
The objective of this study is to examine the inheritance of lipid and lipoprotein levels and the physical properties, as well as chemical composition, of human plasma proteins in order to obtain insights on how to control heart diseases.
METHODOLOGY
Up to 80cc of blood are drawn from subjects via venipuncture. Additionally, a medical interview is conducted with each subject in which demographic information, family/personal health history, dietary, exercise and smoking habits, etc., are requested.
INVOLVEMENT OF AND RISKS TO HUMAN SUBJECTS
The risks are those common to venipuncture (bruising, slight risk of infection). Please note that the figure given for Number of Human Subjects, is the number of samples collected; some subjects may have given multiple samples.
CONFIDENTIALITY
Collection of samples is not anonymous. Subjects are informed that a portion of the blood will be stored for possible future analysis by collaborating investigators. Lipoprotein analysis results are supplied to the subject's personal physician only when requested by the subject.
Institutional Review Board (IRB) Review:
Type of Review: Expedited
Approving Institution: Lawrence Berkeley National Laboratory
Most recent approval: 02/09/01
IRB approval number: 2001-2-25
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:
TITLE: Blood Donations for Transgenic Studies
OBJECTIVES
The objective of this study is to produce mice that carry specific human transgenes. This will enable researchers to study the phenotypic effects of specific genes in an animal model.
METHODOLOGY
Subjects will be recruited from the "Blood Donations for Family Studies" protocol (MM2337). Up to 80cc of blood is drawn via venipuncture. Additionally, a medical interview is conducted with each subject in which demographic information, family/personal health history, dietary, exercise and smoking habits, etc., are requested. DNA will be obtained for the white blood cells and used as a source of transgenes.
INVOLVEMENT OF AND RISKS TO HUMAN SUBJECTS
The risks are those common to venipuncture (bruising, slight risk of infection). Subjects are also informed that there is no plan for them to share in any income arising from the new transgenic mouse strains.
CONFIDENTIALITY
Collection of samples is not anonymous, but samples are supplied to the transgenic facility anonymously. The identity of the human gene donors will not be linked to the resultant mouse strains.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Lawrence Berkeley National Laboratory
Most recent approval: 02/09/01
IRB approval number: 2001-2-24
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 423
Reporting period for number of human subjects:
Year prior to last IRB approval date
Type(s) of Human Subjects Involvement:
TITLE: Blood Donations for Lipoprotein Research
OBJECTIVES
The objective of this study is to obtain blood for isolation of lipoproteins and plasma proteins, and as a source of lipids for lipoprotein interaction studies. Since certain lipoproteins have been indicated as predisposing individuals to arteriosclerosis and heart disease, this study aims to obtain insights on how to control such diseases.
METHODOLOGY
Not more than a unit of blood (500cc) will be drawn from donors by venipuncture. Blood bank criteria will be used in determining the frequency of donor use. Some donors may be asked to fast overnight prior to blood withdrawal.
INVOLVEMENT OF AND RISKS TO HUMAN SUBJECTS
Risks are those common to venipuncture (bruising, mild risk of infection). Please note that the figure given for Number of Human Subjects, is the number of samples collected; some subjects may have given multiple samples.
CONFIDENTIALITY
Collection of samples is not anonymous. Subjects are informed that a portion of the blood will be stored for possible future analysis by collaborating investigators. Lipoprotein analysis results are supplied to the subject's personal physician only when requested by the subject.
"Characterization of Human Mammary Cells"
Principal Investigator: Dr. Martha R. Stampfer, Lawrence Berkeley National Laboratory
Project started in: 1979
Funding for Human Subjects Research:
This project involves the use of multiple protocols/subprojects.
Number of protocols/subprojects associated with this project: 2
Institutional Review Board (IRB) Review:
Type of Review: Expedited
Approving Institution: Lawrence Berkeley National Laboratory
Most recent approval: 04/17/01
IRB approval number: 2001-4-91
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:
This research is concerned with the growth control of human breast cells and the relationship of differentiation with transformation.
Human milk contains a small number of living cells that have been sloughed off from the breast tissue during the secretory process. These sloughed cells are isolated from human milk samples and studied to gain an insight into the events taking place within the breast tissue.
Subjects are asked to provide information relating to their general health, age, race, and birth of their child. They express one or more samples of breast milk using their own equipment in the privacy of their home. As subjects are performing this process on a regular basis, no risk directly related to the research is anticipated.
These samples are not collected anonymously. However, when tissue samples or cell cultures are made available to other researchers they are identified only by code number. Subjects are informed as part of the consent process that their samples may be used by others.
Institutional Review Board (IRB) Review:
Type of Review: Expedited
Approving Institution: Lawrence Berkeley National Laboratory
Most recent approval: 04/17/01
IRB approval number: 2001-4-91
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:
The investigator's goal is to determine the morphological, biological, and biochemical properties associated with normal, atypical, and malignant mammary epithelial cells. Such studies will elucidate mechanisms of human carcinogenesis and aid clinicians in the early detection of breast cancer.
The research will use portions of residual tissues from medical procedures such as aspiration of cysts, mammary biopsies, reduction mammoplasty, or mastectomy. Residual tissues from other sites (e.g., skin, cervix) may also be obtained. Samples are identified by patient number and donor location and may be accompanied by medical history data.
Collection of the samples poses no additional risk to the subject. Samples are only obtained from subjects who have given permission for the research use of their tissues.
These samples are not collected anonymously, but arrive at the Laboratory already identified by code number.
"Myocardial Flow, Function, and Metabolism by PET & MRI"
Principal Investigator: Dr. Thomas F. Budinger, Lawrence Berkeley National Laboratory
Project started in: 1980
Funding for Human Subjects Research:
This project involves the use of multiple protocols/subprojects.
Number of protocols/subprojects associated with this project: 3
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Lawrence Berkeley National Laboratory
Most recent approval: 08/25/00
IRB approval number: 2000-8-118
Explanation of IRB approval:
Renewal of this protocol is pending submission of a major modification by the researcher.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Other: 08/25/00 to 08/24/01
Explanation:
Period between the last IRB review and approval and expiration of the protocol.
Type(s) of Human Subjects Involvement:
TITLE: Coronary Artery Disease Evaluation by Quantitative Perfusion Studies Using 13NH3 and PET
OBJECTIVES
The purpose of this project is to develop noninvasive, rapid, and economical methods for the evaluation of cardiac ischemia. This protocol will evaluate the clinical utility of quantitative heart perfusion data obtained with the radiotracer 13-nitrogen ammonia (13NH3) and Positron Emission Tomography (PET).
The PET scan may provide information that could benefit the patient in his/her overall therapy management, but such a benefit is not assured. Society would benefit from improved and more economical diagnostic tests.
METHODOLOGY
A catheter will be placed in a vein in one arm to inject the radiotracers and to collect blood samples to verify the rate at which the radiotracer is cleared from the blood. A blood glucose test will be performed, and patients with blood sugars less that 120 mg% will receive oral glucose loading. After positioning the subject in the PET scanner, a transmission scan without radiotracer will be done to allow corrections of the emission data. Next the first 35 mCi dose of 13NH3 is injected and a resting PET scan is taken. Between 30 and 40 minutes after the initial tracer injection, dipyridamole will be infused intravenously. The second 13NH3 injection is given about 4 minutes after the perfusion is completed and the final PET scan begins shortly thereafter. Subjects may not move during the scans. The total procedure should take about 120 minutes.
RADIATION/CHEMICAL SUBSTANCES
13-nitrogen ammonia; dipyridamole
INVOLVEMENT OF HUMAN SUBJECTS
Risks include: venous catheter (bruising, faintness); radiation (equivalent to kidney x-ray); and the routine risks associated with any clinical use of dipyridamole (occasional severe chest pain, severe hypotension, respiratory distress, and vomiting or nausea; rarely, symptoms of myocardial ischemia requiring the use of aminophylline to reverse the effect; very rarely, heart attack or death).
CONFIDENTIALITY
The identities of the subjects are known, but any public report is by code numbers only. Results from PET scans are supplied to the patients' personal physicians. Subjects are reminded that the Food and Drug Administration may have access to their records and that research records are not immune to subpoena.
NOTE: The number of subjects participating under this protocol is reported under "Experimental Medicine Clinical" (LBNL 75-001-H02). Additional subjects were not studied under this project, therefore, the number of subjects reported here is zero to prevent counting the same subjects twice.
RENEWAL OF THIS PROTOCOL IS PENDING A MAJOR REVISION BY THE RESEARCHER. NO SUBJECTS WILL BE STUDIED UNDER THE PROTOCOL UNTIL IT IS AGAIN FULLY APPROVED BY THE INSTITUTIONAL REVIEW BOARD.
Institutional Review Board (IRB) Review:
Type of Review: Expedited
Approving Institution: Lawrence Berkeley National Laboratory
Most recent approval: 10/17/01
IRB approval number: 2001-10-72
Explanation of IRB approval:
Approval is based on review of another IRB which did occur during FY 2001.
Additional IRB approvals from other institutions:
Type of Review: Full Board
Approving Institution: University of California at San Francisco
Most recent approval: 08/23/01
IRB approval number: H5637-15423-04
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 9
Reporting period for number of human subjects:
Year prior to last IRB approval date
Type(s) of Human Subjects Involvement:
TITLE: Evaluation of the Benefits of Motion Compensation in Cardiac Positron Emission Tomography (PET) with Respiratory and Cardiac Gating
OBJECTIVES
The purpose of this project is to evaluate the utility of motion compensation in cardiac PET studies. The individual subjects will be healthy volunteers and will not benefit from the research. Society would benefit from more accurate and economical diagnostic tests.
18F-fluorodeoxyglucose (FDG) studies to determine which is the superior technique.
METHODOLOGY
Up to 20 healthy human volunteers will be sought through advertisement. Subjects will receive a standard PET scan, described below, with one or two rubber bellows placed around the torso to monitor breathing movement.
Subjects are offered water before their study begins. A catheter will be placed in a vein in one arm to inject the radiotracer and to collect blood samples to verify the rate at which the radiotracer is cleared from the blood. First a transmission scan without radiotracer is performed to allow corrections of the emission data. Subjects will then receive one injection of 18F-fluorodeoxyglucose (FDG). Subjects may not move during the scans. The total procedure should take two to two-and-a-half hours.
RADIATION/CHEMICAL SUBSTANCES
18F-fluorodeoxyglucose (FDG)
INVOLVEMENT OF AND RISKS TO HUMAN SUBJECTS
PET scan risk includes: venous catheter (bruising, faintness); radiation (equivalent to kidney x-ray).
There is no increase in risk associated with use of the rubber bellows.
CONFIDENTIALITY
The identities of the subjects are known, but any public report is by code numbers only. Subjects are reminded that the Food and Drug Administration may have access to their records and that research records are not immune to subpoena.
These PET studies are carried out at the University of California, San Francisco.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Lawrence Berkeley National Laboratory
Most recent approval: 08/25/00
IRB approval number: 2000-8-124
Explanation of IRB approval:
Renewal of this protocol is pending submission of a major revision by the researcher.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Other: 08/25/00 to 08/24/01
Explanation:
Period between last IRB review and approval and expiration of the protocol.
Type(s) of Human Subjects Involvement:
TITLE: Coronary Artery Disease Evaluation by 13-Ammonia Perfusion and Deoxyglucose Uptake Measured by PET and Three-Dimensional MR Myocardial Tagging
OBJECTIVES
The purpose of this project is to develop noninvasive, rapid, and economical methods for the evaluation of myocardial perfusion and metabolism. This protocol will compare magnetic resonance imaging (MRI) strain data from rest and low dose dobutamine stress conditions to PET 13-ammonia/18F-fluorodeoxyglucose (FDG) studies to determine which is the superior technique. The PET scan may provide information that could benefit the patient in his/her overall therapy management, but such a benefit is not assured. Society would benefit from improved and more economical diagnostic tests.
METHODOLOGY
MRI: The standard medical procedure for myocardial tagging image will be used. Subjects will discontinue beta-blocker medications 48 hours before the procedure (with the permission of their personal physician/cardiologist). A venous catheter will be placed and heart rate and blood pressure monitors attached. After a resting MRI, dobutamine will be administered as a cardiac stressor. Drugs to counteract the effect of the dobutamine, if needed, will be on hand.
PET: Patients will fast the night before scanning. Subjects are offered water before their study begins. A catheter will be placed in a vein in one arm to inject the radiotracers and to collect blood samples to verify the rate at which the radiotracer is cleared from the blood. First the 13-ammonia scan is performed. Subjects are then allowed to void if necessary. Then a transmission scan without radiotracer is performed to allow corrections of the emission data. Lastly, the 18-FDG study is done. Subjects may not move during the scans. The total procedure should take about 120 minutes.
RADIATION/CHEMICAL SUBSTANCES
MRI: dobutamine
PET: Fluorine-18 fluorodeoxyglucose; nitrogen-13 ammonia
INVOLVEMENT OF HUMAN SUBJECTS
Each of the subjects will have two MRI studies but most subjects will have only a single 13-ammonia vs. 18-FDG uptake PET study.
MRI risks include: venous catheter (bruising, faintness); the discomfort of lying still in an enclosed space for a long period of time; the rare chance of an allergic reaction to dobutamine; the possibility of discomfort associated with discontinuing medication 48 hours prior to the study; and the rare possibility (as with any stress test) of arrhythmia, heart attack, or death.
PET scan risk includes: venous catheter (bruising, faintness); radiation (equivalent to kidney x-ray).
CONFIDENTIALITY
The identities of the subjects are known, but any public report is by code numbers only. Results from PET and or MRI are supplied to the patients' personal physicians. Subjects are reminded that the Food and Drug Administration may have access to their records and that research records are not immune to subpoena.
NOTE: The number of subjects participating under this protocol is reported under "Experimental Medicine Clinical" (LBNL 75-001-H02). Additional subjects were not studied under this project, therefore, the number of subjects reported here is zero to prevent counting the same subjects twice.
RENEWAL OF THIS PROTOCOL IS PENDING A MAJOR REVISION BY THE RESEARCHER. NO SUBJECTS WILL BE STUDIED UNDER THE PROTOCOL UNTIL IT IS AGAIN FULLY APPROVED BY THE INSTITUTIONAL REVIEW BOARD.
"Alzheimer's Disease as a Systemic Disorder"
Principal Investigator: Dr. Thomas F. Budinger, Lawrence Berkeley National Laboratory
Project started in: 1984
Funding for Human Subjects Research:
This project involves the use of multiple protocols/subprojects.
Number of protocols/subprojects associated with this project: 4
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Lawrence Berkeley National Laboratory
Most recent approval: 10/06/00
IRB approval number: 2000-10-56
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Other: 10/06/00 to 08/30/01
Explanation:
Final period during which protocol was approved.
Type(s) of Human Subjects Involvement:
TITLE: Skeletal Muscle Metabolism in Alzheimer's Disease
OBJECTIVES
Alzheimer's disease (AD) is known to be associated with change in cerebral glucose metabolism, and it has been suggested that AD is also associated with changes in muscular glucose utilization. The goal of this study is to quantify skeletal muscle glucose metabolism in subjects with Alzheimer's disease.
METHODOLOGY
An equal number of control subjects and AD patients will be recruited. Patient subjects are accompanied by an adult family member or guardian to assure an appropriate consent process. AD patients will have been previously evaluated by their treating clinic and these results will be made available to the researchers.
On the day of the study, subjects will fast for about two hours. They will then be given a light meal. A detailed exercise history for the week prior to the study will be taken. A small sample of venous blood will be drawn for insulin assay; blood glucose may be adjusted using glucola.
Subjects will lie on their stomachs with their legs through the ring of the PET scanner. The subject will exercise by repeatedly depressing a foot pedal for at least 15 minutes. The radiotracer F-18-fluorodeoxyglucose will be administered about 3 minutes into the exercise session. After the leg exercise and scan, subjects will urinate to reduce the dose to the bladder and then repositioned in the PET scanner for a brain scan. No additional radiotracer will be given.
Vascular reactivity to the tightening and releasing of a blood pressure cuff will also be non-invasively measured using a Food and Drug Administration approved Doppler flow system.
IONIZING RADIATION, RADIOACTIVE SUBSTANCES, OR CHEMICAL SUBSTANCES
Fluorine-18 Fluorodeoxyglucose
INVOLVEMENT OF AND RISKS TO HUMAN SUBJECTS
PET scan risk includes: venous catheter (bruising, faintness) and radiation (equivalent to back x-ray).
Other risks include muscle fatigue or cramping from depressing the pedal and discomfort due to the squeezing of the blood pressure cuff.
CONFIDENTIALITY
The identities of the subjects are known, but any public report is by code numbers only. The results from the venous blood analysis are supplied to the patients' personal physicians upon request. Subjects are reminded that the Food and Drug Administration may have access to their records and that research records are not immune to subpoena. In patients whose cognition is or may be impaired, the consent of the responsible next of kin or conservator as well as the assent of the patient will be sought.
THIS PROTOCOL WAS DISCONTINUED IN AUGUST 2001.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Lawrence Berkeley National Laboratory
Most recent approval: 08/25/00
IRB approval number: 2000-8-117
Explanation of IRB approval:
Renewal of this protocol is still pending; the researcher will be submitting a major revision.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Other: 08/25/00 to 08/25/01
Explanation:
Period between the last IRB review and approval and expiration of the protocol.
Type(s) of Human Subjects Involvement:
OBJECTIVES
The objectives of this study are to utilize magnetic resonance imaging (MRI) and positron emission tomography (PET) on patients with Alzheimer's disease, Parkinson's disease, and multi-infarct dementia to understand the longitudinal effects of these conditions on cerebral metabolism and to develop a new serotonin-based radiotracer which will provide a measure of the presynaptic degeneration in these cases; correlate the presynaptic degeneration with behavioral changes. The new tracer will also be used to investigate serotonergic degeneration in these diseases. Societal benefits may include a greater understanding of dementing illnesses.
METHODOLOGY
Subjects are accompanied by an adult family member or guardian to assure an appropriate consent process. Subjects are offered water before their study begins. A catheter will be placed in a vein in one arm and another will be placed in an artery or vein of the hand on the other arm. The venous catheter will be used to inject the radiotracer and the arterial (or other venous) catheter will be used to collect blood samples to verify the rate at which the radiotracer is cleared from the blood. After a half-hour uptake phase, subjects are asked to empty their bladder to keep the radiation exposure to the bladder as low as possible. Subjects then watch a video display terminal on which words are presented. A delayed word presentation is used to determine the duration of subjects' memory. Subjects are then positioned in the PET scanner, where the technician provides blankets and padding in order to make them as comfortable as possible. Subjects may not move during the scan, which may last 60 to 90 minutes. Subsequently, the subjects may be placed in a MRI scanner for 2 scans totaling approximately 30 minutes.
IONIZING RADIATION, RADIOACTIVE SUBSTANCES, OR CHEMICAL SUBSTANCES
Fluorine-18 Fluorodeoxyglucose
INVOLVEMENT OF AND RISKS TO HUMAN SUBJECTS
PET scan risk includes: venous catheter (bruising, faintness); arterial catheter (bruising, pain, faintness); radiation (equivalent to back x-ray). If an arterial catheter is to be placed, lidocaine is used to provide local anesthesia before placing the catheter.
MRI scan risk includes discomfort associated with lying still in an enclosed space.
CONFIDENTIALITY
The identities of the subjects are known, but any public report is by code numbers only. Results from PET and/or MRI are supplied to the patients' personal physicians. Subjects are reminded that the Food and Drug Administration may have access to their records and that research records are not immune to subpoena. In patients whose cognition is or may be impaired, the consent of the responsible next of kin or conservator as well as the assent of the patient will be sought.
RENEWAL OF THIS PROTOCOL IS PENDING A MAJOR REVISION BY THE RESEARCHER. NO SUBJECTS WILL BE STUDIED UNDER THE PROTOCOL UNTIL IT IS AGAIN FULLY APPROVED BY THE INSTITUTIONAL REVIEW BOARD.
Institutional Review Board (IRB) Review:
Type of Review: Expedited
Approving Institution: Lawrence Berkeley National Laboratory
Most recent approval: 03/14/01
IRB approval number: 2001-3-51
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 11
Reporting period for number of human subjects:
Year prior to last IRB approval date
Type(s) of Human Subjects Involvement:
TITLE: Cardiovascular Relationships in Alzheimer's Disease --Determination of Peripheral Vascular Reactivity
OBJECTIVES
The goal of this study is to demonstrate the presence or absence of strong correlations between Alzheimer's disease (AD) and peripheral cardiovascular disease. Societal benefits may include a greater understanding of dementing illnesses.
METHODOLOGY
An equal number of control subjects and AD patients will be recruited. Patient subjects are accompanied by an adult family member or guardian to assure an appropriate consent process. AD patients will have been previously evaluated by their treating clinic and these results will be made available to the researchers.
On the day of the study, a small sample of venous blood will be drawn for lipoprotein analysis in order to correlate LDL levels, reactivity and subject illness. Vascular reactivity to the tightening and releasing of a blood pressure cuff will then be non-invasively measured using a Food and Drug Administration approved Doppler flow system.
IONIZING RADIATION, RADIOACTIVE SUBSTANCES, OR CHEMICAL SUBSTANCES
None
INVOLVEMENT OF AND RISKS TO HUMAN SUBJECTS
Study risks include: venous catheter (bruising, faintness), discomfort due to the squeezing of the blood pressure cuff.
CONFIDENTIALITY
The identities of the subjects are known, but any public report is by code numbers only. The results from the venous blood analysis are supplied to the patients' personal physicians upon request. Subjects are reminded that the Food and Drug Administration may have access to their records and that research records are not immune to subpoena. In patients whose cognition is or may be impaired, the consent of the responsible next of kin or conservator as well as the assent of the patient will be sought.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Lawrence Berkeley National Laboratory
Most recent approval: 02/06/01
IRB approval number: 2001-4-92
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 7
Reporting period for number of human subjects:
Year prior to last IRB approval date
Type(s) of Human Subjects Involvement:
TITLE: Evaluation of Vascular Reactivity in Alzheimer's Disease via Iontophoresis of Vasoactive Compounds
OBJECTIVES
The goal of this study is to continue to examine the presence or absence of strong correlations between Alzheimer's disease (AD) and peripheral cardiovascular disease. Societal benefits may include a greater understanding of dementing illnesses.
METHODOLOGY
An equal number of control subjects and AD patients will be recruited. Patient subjects are accompanied by an adult family member or guardian to assure an appropriate consent process. AD patients will have been previously evaluated by their treating clinic and these results will be made available to the researchers.
On the day of the study, subjects will be screened for factors such as the use of aspirin. A small sample of venous blood will be drawn for lipoprotein analysis in order to correlate LDL levels, reactivity and subject illness. A picture of the blood vessels in the hand will be taken using a laser scanner. The laser is similar in intensity to a laser pointer and is not damaging to the skin.
Areas of the skin will be cleaned using isopropyl alcohol. Small amounts of up to five vasodilators and/or constrictors will be dabbed onto the subject's skin. A one inch square electrode will be placed over the applied chemical, and a tiny electric current applied to cause the chemical to move into localized areas the skin and underlying capillaries. Changes in the circulation will then be non-invasively measured using the same non-invasive laser scanner described above.
IONIZING RADIATION, RADIOACTIVE SUBSTANCES, OR CHEMICAL SUBSTANCES
The vasodilators and/or constrictors which may be applied to localized areas of the skin of the arm are: sildenafil citrate; nitro-L-arginine methy ester; nitroprusside; methacholine; acetylcholine. None of the applications will result in a significant or even measurable systemic dose.
INVOLVEMENT OF AND RISKS TO HUMAN SUBJECTS
Study risks include: venous catheter (bruising, faintness); minor skin irritation or allergic reaction from the chemicals applied to the skin; a slight, transient tingling feeling from the iontophoresis electrode.
CONFIDENTIALITY
The identities of the subjects are known, but any public report is by code numbers only. The results from the venous blood analysis are supplied to the patients' personal physicians upon request. Subjects are reminded that research records are not immune to subpoena. In patients whose cognition is or may be impaired, the consent of the responsible next of kin or conservator as we