Ms. Mona Rowe
Brookhaven National Laboratory
Bldg. 134
Upton, NY 11973-5000
Phone: 631-344-2345
Fax: 631-344-3368
E-mail: mrowe@bnl.gov
Number of Human Subjects projects reported: 51
"Evaluation of 18-FDG in the Diagnosis of Glucose Metabolism in the Human Body (Alzheimer's)"
Principal Investigator: Dr. Joanna S. Fowler, Brookhaven National Laboratory
Project started in: 1994
This project ended in fiscal year 2001.
Funding for Human Subjects Research: No Funding Sources Reported
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Brookhaven National Laboratory
Most recent approval: 12/05/00
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 primary hypothesis of this protocol is that among non-demented elderly (ranging from normal through minimum impairment) hippocampal metabolic changes as measured by 18-FDG (fluoro-deoxyglucose) PET scans precede cognitive deterioration, the clinical diagnosis of dementia and metabolic neocortical changes. Subjects will have annual longitudinal follow up positron emission tomography (PET) studies and we will analyze all longitudinal studies (baseline and follow up) with respect to our hypothesis. Our preliminary analysis shows that the size of the hippocampus at the baseline, using magnetic resonance imaging (MRI), predicts the neocortical regional brain glucose metabolism change at follow up. In other words, those cases with smaller hippocampi had reduced neocortical cerebral metabolic rate of glucose (CMRglu) on their follow up PET scans, suggesting that the first site of pathology is the hippocampus.
Subjects have a short-lived positron emitter tracer administered and are subsequently scanned with PET. A potential side effect of radiation is the induction of cancer. However, no harm in a human individual or in a large population exposed at doses as low as those delivered in this procedure (2530 mrem) has been reported. The estimation of risk of harm can be obtained only by extrapolation from much higher doses. Arterial catheterization has the following rare but possible complications: pain during placement of the catheter, a risk of bleeding at the skin puncture site, the possibility of local infection and temporary or permanent impairment of the blood supply to portions of the hand. Whenever blood is removed or a substance is injected by venipuncture, there is minor discomfort and a slight possibility of local bleeding in the tissues.
All records are confidential and may not be disclosed without the subject's written permission with the exception that the FDA and/or funding agencies may inspect the records. Documented informed consent is obtained from all subjects in a manner compliant with all federal regulations.
"General Magnetic Resonance Imaging (MRI) and Spectroscopic (MRS) Studies of Human Subjects"
Principal Investigator: Dr. Charles S. Springer, Brookhaven National Laboratory
Project started in: 1996
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Brookhaven National Laboratory
Most recent approval: 06/19/01
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Year prior to last IRB approval date
Type(s) of Human Subjects Involvement:
The goal of this proposal is to evaluate tissue MR signal relaxivities at the 4T field strength and to conduct research aimed at increasing our understanding of the mechanisms and evolution of normal brain function and human disease states. This work will not be used for routine diagnosis. About 300 studies, all of normal adult volunteers, are ultimately expected to be made in a year. No radiopharmaceuticals (drugs) or surgical procedures will be used in this study. Each participant will be asked to complete an entry questionnaire prior to completing a consent form and being allowed into the magnet. The purpose of the entry questionnaire is to screen out individuals who may have problems in the magnet caused by metal implants, claustrophobia, etc. During the study, the subjects will be monitored using a video camera and communicated with via a two-way intercom, from the control room where the operator is located. After the study, the subjects will be asked to complete an exit form, which is to document any feeling they may have experienced during the 4T scanning. No serious ill effects have been reported to date from any of the six research facilities in the United States operating with this magnetic field strength (4T). Because of the strong magnetic field, individuals with surgically implanted metallic devices such as clips, artificial joints, certain heart valves and pacemakers will be excluded from this study, as well as subjects with claustrophobia. The possible risks due to the magnet itself are primarily related to the slight possibility of a sensation of dizziness or nausea as the subject moves in and out of the magnet or moves their head in the magnet. The magnet is thought to be able to exert a force on the fluid within the semicircular canals near the ears, thus giving a sensation of disequilibrium. The sensations go away if the head is not in motion or if the individual is not moving in and out of the magnet. Subjects are exposed to noise from the machine, for which earplugs are provided. All records are confidential and may not be disclosed without the subject's written consent with the exception that the FDA and/or funding agencies may inspect the records. Documented informed consent is obtained from all subjects in a manner compliant with all federal regulations.
"99m Tc DTPA Lung Clearance in Radiation Injury"
Principal Investigator: Mr. Herbert Susskind, Brookhaven National Laboratory
Project started in: 1997
This project ended in fiscal year 2001.
Funding for Human Subjects Research: No Funding Sources Reported
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Brookhaven National Laboratory
Most recent approval: 12/14/99
Explanation of IRB approval:
Protocol was inactivated 10/00
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 purpose of this study is to evaluate the lung clearance of inhaled 99m Tc diethylenetriaminepentaacetic acid (DTPA) to detect radiation pneumonitis as early as possible. Twenty subjects with lung or breast carcinoma undergoing radiation therapy will be studied to determine 1) If two DTPA measurements will permit the investigators to predict which subjects will develop radiation pneumonitis; 2) the relationship between DTPA clearance and blood plasma levels of enzyme inhibitors and matrix metalloproteinases that degrade lung interstitial matrix; and 3) the relationship between DTPA clearance and pulmonary function tests, carbon monoxide diffusing capacity measurements, and chest radiographs and CT scans. Subjects will be seated in front of a gamma camera and 99m Tc DTPA will be delivered through the mouth by an aerosol delivery system, while the subject will breath normally for 3-4 minutes. The subject will be scanned by the gamma camera for 25 minutes. The results will be compared to x-rays taken, and blood plasma levels of certain enzymes and inhibitors will be measured from blood samples taken during and following the clinical radiation therapy treatment. A potential side effect of radiation is the induction of cancer. However, no harm in a human individual or in a large population exposed at doses as low as those delivered in this procedure has been reported. The estimation of risk can be obtained only by extrapolation from much higher doses. All records are confidential and may not be disclosed without the subject's written consent with the exception that the FDA and/or funding agencies may inspect the records. Documented informed consent is obtained from all subjects in a manner compliant with all federal regulations.
"Brain Imaging Studies in Methamphetamine Abusers"
Principal Investigator: Dr. Joanna S. Fowler, Brookhaven National Laboratory
Project started in: 1998
This project ended in fiscal year 2001.
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Brookhaven National Laboratory
Most recent approval: 10/01/00
Explanation of IRB approval:
Protocol was inactivated by the PI 4/01
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Other: 10/01/00 to 04/01/01
Explanation:
Protocol was inactivated 04/01
Type(s) of Human Subjects Involvement:
The purpose of this study is to investigate if there are changes in the brain DA system of methamphetamine abusers and to assess if these changes are reversible. We will assess the brain DA system using Positron Emission Tomography (PET) and a multiple tracer approach to evaluate the various elements of the DA synapse in 10 recently detoxified methamphetamine abusers and in 10 former methamphetamine abusers. The dopamine transporters, which serve as markers for the dopamine presynaptic elements, will be evaluated using [11C]d threo methylphenidate and the DA D2 receptors, which serves as markers of DA postsynaptic elements, will be evaluated with [11C]raclopride. Brain glucose metabolism will also be measured in these subjects using 2-deoxy-2-[18F]fluoro-D-Glucose (18FDG) to measure brain function. This will allow us to determine if methamphetamine is toxic to DA synapses and to assess if they recover with protracted detoxification. The measurement of brain glucose metabolism with 18FDG will allow us to explore relationships between dopamine activity and brain function. We will use as comparison the normative data already available for healthy controls who have been scanned with the same tracers at Brookhaven National Laboratory. A potential side effect of radiation is the induction of cancer. However, no harm in a human individual or in a large population exposed at the doses as low as those delivered in this procedure (1720 mrem) has been reported. The estimation of risk of harm can be obtained only by extrapolation from much higher doses. All records are confidential and may not be disclosed without the subject's written consent with the exception that the FDA and/or funding agencies may inspect the records. Documented informed consent is obtained from all subjects in a manner compliant with all federal regulations.
"Spectroscopic Studies in Drug Abusers"
Principal Investigator: Dr. Nora D. Volkow, Brookhaven National Laboratory
Project started in: 1998
This project ended in fiscal year 2001.
Funding for Human Subjects Research: No Funding Sources Reported
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Brookhaven National Laboratory
Most recent approval: 12/05/00
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 purpose of this study is to evaluate the gamma-aminobutyric acid (GABA) system (GABA is the chemical by which brain processes are inhibited) in cocaine abusers and alcoholics and its relationship to withdrawal and detoxification. Subjects will be scanned with Magnetic Resonance Spectroscopic Imaging (MRSI) to measure the regional brain concentrations of GABA. Each subject will be scanned three different times. For substance abusers, the first time will be 5-10 days after last use of drug/alcohol; the second time will be 4-6 weeks after last use of drug/alcohol; and the third time will be 6 months after last use of drug/alcohol. For normal controls, the same time intervals will be used to control for test-retest variability in the measurements. No pharmaceuticals or radiopharmaceuticals will be given.
Twenty normal controls, twenty drug abusers and twenty alcoholics, males and females in the age range of 20-60, will be studied.
All records are confidential and may not be disclosed without the subject's written permission with the exception that the FDA and/or funding agencies may inspect the records. Documented informed consent is obtained from all subjects in a manner compliant with all federal regulations.
"PET Studies of L-Deprenyl (Selegiline)"
Principal Investigator: Dr. Joanna S. Fowler, Brookhaven National Laboratory
Project started in: 1998
This project ended in fiscal year 2001.
Funding for Human Subjects Research: No Funding Sources Reported
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Brookhaven National Laboratory
Most recent approval: 06/06/00
Explanation of IRB approval:
Protocol was inactivated by PI 10/00
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: 06/01/00 to 10/01/00
Explanation:
Protocol was inactivated 10/00
Type(s) of Human Subjects Involvement:
L-Deprenyl (selegiline) is a specific inhibitor of monoamine oxidase B (MAO B), a brain enzyme which breaks down neurotransmitter amines including dopamine. It has been used for many years in the treatment of Parkinson's disease in order to spare brain dopamine from enzymatic breakdown. It also has been postulated to have neuroprotective properties. In two recent clinical studies, chronic L-deprenyl treatment was reported to (1) provide beneficial therapeutic effects in the treatment of cocaine abuse in 1 out of 5 subjects and (2) to reduce the magnitude of the cocaine-induced high in cocaine abusers. However, in spite of its clinical use, there is little known about the effects of L-deprenyl on the human brain other than its ability to inhibit MAO B. There is evidence from animal studies and post-mortem human brain that chronic L-deprenyl treatment also partially inhibits MAO A and that it alters the dopamine transporter. We propose to use PET to assess the effects of chronic L deprenyl (1-4 weeks) on MAO A (using [11C]clorgyline) and on dopamine transporter availability (using [11C]cocaine) in 5 normal subjects treated with L-deprenyl for 4 weeks. These studies will use 5 normal subjects who will be scanned with both tracers at baseline and again after 1-4 weeks on L-deprenyl.
These studies will provide the first direct measures in the living human brain delineating the molecular pharmacology of a drug which has potential for the treatment of cocaine abuse and about which there is surprisingly little mechanistic knowledge. We will recruit 8 subjects to compensate for possible drop-outs. A potential side effect of radiation is the induction of cancer. However, no harm in a human individual or in a large population exposed at the doses as low as those delivered in this procedure (585 mrem) has been reported. The estimation of risk of harm can be obtained only by extrapolation from much higher doses. Methylphenidate is a mild central nervous system stimulant used to treat attention deficit disorder and narcolepsy. It increases heart rate and blood pressure and can cause a behavioral "high". It can also elicit negative feelings of anxiety. In the event that either cardiovascular or behavioral complications occur, they can be effectively treated with an intramuscular injection of a neuroleptic. Since methylphenidate will be administered orally, the likelihood of cardiac stimulation is lower. There is also some evidence that methylphenidate may lower the seizure threshold in some individuals who have a prior history of seizure disorders. Therefore, methylphenidate will not be given to patients with cardiac disease or patients with seizure disorders. All records are confidential and may not be disclosed without the subject's written permission with the exception that the FDA and/or funding agencies may inspect the records. Documented informed consent is obtained from all subjects in a manner compliant with all federal regulations.
"Brain Water Content and Blood-Brain Barrier Permeability in Multiple Sclerosis"
Principal Investigator: Dr. William Rooney, Brookhaven National Laboratory
Project started in: 1998
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Brookhaven National Laboratory
Most recent approval: 07/24/01
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Year prior to last IRB approval date
Type(s) of Human Subjects Involvement:
Multiple sclerosis (MS) is a chronic disease of the central nervous system of unknown etiology. The primary disease process is thought to be an autoimmune attack directed against myelin, a fatty substance that insulates nerve fibers, and possibly other components. Although the presence of demyelinating lesions is the pathological hallmark of MS, considerable evidence suggests that white matter which is macroscopically devoid of lesions, is also abnormal. This application proposes a quantitative magnetic resonance imaging study of multiple sclerosis patients and health controls to determine if 1) water content is increased in normal appearing white matter; 2) the blood-brain barrier permeability is increased in Normal Appearing White Matter (NAWM) in MS; and 3) increased water-brain-water content or blood-brain barrier permeability are predictive of disease progression. Twenty-five normal controls and 25 patients with MS will undergo three contrast-enhanced MRI studies at six month intervals. All records are confidential and may not be disclosed without the subject's written permission with the exception that the FDA and/or funding agencies may inspect the records. Documented informed consent is obtained from all subjects in a manner compliant with all federal regulations.
"PET Studies of Alcoholism: Measurement of Brain Glucose Metabolism and Dopamine Activity in Alcoholics During Early and Late Detoxification"
Principal Investigator: Dr. Nora D. Volkow, Brookhaven National Laboratory
Project started in: 1999
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Brookhaven National Laboratory
Most recent approval: 07/24/01
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 34
Reporting period for number of human subjects:
Other: 08/06/00 to 07/09/01
Explanation:
This is the time period of the annual recertification. The number of subjects refers to the number enrolled (34) and includes those completed (10), those who failed screening and those who withdrew or who were withdrawn (24). There were 10 subjects completed
Type(s) of Human Subjects Involvement:
Dopamine is a chemical compound in the brain which is important in movement and in feelings of reward and well-being. Recent PET imaging studies have shown that dopamine activity and brain metabolism are abnormally low in alcoholics. An important question is whether these systems recover when subjects withdraw from alcohol. To do this, a PET camera will be used to visualize dopamine activity (using [11C]raclopride and [11C]d-threo-methylphenidate or [11C]cocaine as tracers) and brain sugar metabolism (using F-18-fluorodeoxyglucose (18FDG) as a tracer) in alcoholics and a comparison group of at-risk and control subjects. Imaging will be done on two different days, 4-6 weeks apart to assess recovery. The radiotracers used are labeled with the short lived isotopes, carbon-11 (half life: 20.4 minutes) and fluorine-18 (half life: 110 minutes). Forty alcoholic subjects, sixteen non-alcoholic subjects and forty subjects at risk for alcoholism will be enrolled in the study in order to complete 16 in each group. The information from this study will add to our understanding of the relationship between changes in brain dopamine activity and brain metabolism and the degree to which deficits recover when alcoholics stop drinking. The use of a control population is necessary as a comparison group. A potential side effect of radiation is the induction of cancer. However, no harm in a human individual or in a large population exposed at the doses as low as those delivered in this procedure has been reported. The estimation of risk of harm can be obtained only by extrapolation from much higher doses. Arterial catheterization has the following rare, but possible, complications: pain during the placement of the catheter, a risk of bleeding at the skin puncture site; the possibility of local infection, and temporary or permanent impairment of the blood supply to portions of the hand. Whenever blood is removed or a substance injected by venipuncture, there is minor discomfort and a slight possibility of local bleeding in the tissues. All records are confidential and may not be disclosed without the subject's written permission with the exception that the FDA and/or funding agencies may inspect the records. Documented informed consent is obtained from all subjects in a manner compliant with all federal regulations.
"PET Studies of Alcoholism: Measurement of Brain Metabolism and Brain Dopamine Concentration with 18FDG and 11C-Raclopride"
Principal Investigator: Dr. Nora D. Volkow, Brookhaven National Laboratory
Project started in: 1999
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Brookhaven National Laboratory
Most recent approval: 07/24/01
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: 08/06/00 to 07/09/01
Explanation:
This is the reporting period for our last IRB recertification.
Type(s) of Human Subjects Involvement:
Dopamine is a chemical compound in the brain which is important in movement and in feelings of reward and well-being. The goal of this study is to find out whether alcoholics and cocaine abusers have different brain dopamine function than non-alcoholic and non cocaine addicted subjects. This will be done with a brain imaging method called positron emission tomography (PET). A PET camera will visualize how much dopamine the brain releases and also how certain brain regions become activated in response to the injection of methylphenidate, a stimulant drug known to release dopamine. Dopamine release will be measured using a radiotracer called [11C]raclopride and brain activation will be measured using a radiotracer called F-18 fluorodeoxyglucose. Both C-11 and F-18 are radioisotopes of short half life. Subjects will be tested on two different days with both of these radiotracers. On one day, they will receive a saline solution and on the other methylphenidate. They will not know on which day they will receive the saline or the methylphenidate. Fifteen alcoholic subjects, ten normal controls and five subjects at risk for alcoholism will be studied. The ability of the human brain to release dopamine in response to a drug challenge as well as its ability to activate certain brain areas is important in understanding human behavior and the mechanisms involved in alcohol and cocaine addiction. A potential side effect of radiation is the induction of cancer. However, no harm in a human individual or in a large population exposed at the doses as low as those delivered in this procedure (1778 mrem) has been reported. The estimation of risk of harm can be obtained only by extrapolation from much higher doses. Arterial catheterization has the following rare, but possible, complications: pain during the placement of the catheter, a risk of bleeding at the skin puncture site; the possibility of local infection, and temporary or permanent impairment of the blood supply to portions of the hand. Whenever blood is removed or a substance injected by venipuncture, there is minor discomfort and a slight possibility of local bleeding in the tissues. All records are confidential and may not be disclosed without the subject's written permission with the exception that the FDA and/or funding agencies may inspect the records. Documented informed consent is obtained from all subjects in a manner compliant with all federal regulations.
"PET Studies in Humans with C-11 Labeled Methadone"
Principal Investigator: Dr. YuShin Ding, Brookhaven National Laboratory
Project started in: 1999
This project ended in fiscal year 2001.
Funding for Human Subjects Research: No Funding Sources Reported
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Brookhaven National Laboratory
Most recent approval: 09/05/00
Explanation of IRB approval:
Protocol was terminated at its annual review
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:
Methadone is widely used clinically to treat heroin abusers. It is also used for sedation and analgesia and for pain treatment, but it is most often used in the detoxification treatment and maintenance of heroin abusers. It is similar in structure to morphine. Although methadone has been in use for some time, it is not clear what constitutes an adequate dose of methadone to use for heroin maintenance. There is also insufficient information on how the drug works in the human brain and body. The purpose of this study is twofold: 1) to examine the pharmacokinetics and determine which parts of methadone bind to the opiod receptor (the molecule that recognizes methadone in cells) in the human brain; and 2) to determine the effects of different doses of methadone. This study will use fifteen normal controls and fifteen heroin abusers who are on methadone maintenance. Each subject will receive one injection of [11C]methadone and [11C]R-(-)methadone. There will be no repeat studies. A potential side effect of radiation is the induction of cancer. However, no harm in a human individual or in a large population exposed at the doses as low as those delivered in this procedure (444 mrem) has been reported. The estimation of risk of harm can be obtained only by extrapolation from much higher doses. Arterial catheterization has the following rare, but possible, complications: pain during the placement of the catheter, a risk of bleeding at the skin puncture site; the possibility of local infection, and temporary or permanent impairment of the blood supply to portions of the hand. Whenever blood is removed or a substance injected by venipuncture, there is minor discomfort and a slight possibility of local bleeding in the tissues. All records are confidential and may not be disclosed without the subject's written permission with the exception that the FDA and/or funding agencies may inspect the records. Documented informed consent is obtained from all subjects in a manner compliant with all federal regulations.
"PET Studies of Cocaine Abuse: Evaluation of Brain GABA Activity"
Principal Investigator: Dr. Joanna S. Fowler, Brookhaven National Laboratory
Project started in: 1999
This project ended in fiscal year 2001.
Funding for Human Subjects Research: No Funding Sources Reported
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Brookhaven National Laboratory
Most recent approval: 02/01/01
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Other: 11/13/00 to 05/02/01
Explanation:
Protocol was inactivated 05/01
Type(s) of Human Subjects Involvement:
Previous PET studies have demonstrated that cocaine abusers brains have significant deficits in dopamine activity. Because dopamine signals are transferred via Gamma Aminobutyric Acid-ergic (GABAergic) pathways, the investigators hypothesize that there is a GABAergic disruption in cocaine abusing subjects. To test this hypothesis, Lorazepam, which directly activates GABA receptors, will be administered. Subjects will be given Lorazepam, then studied with a Positron Emission Tomograph (PET), a medical imaging instrument, and 18FDG, a radiotracer labeled with F-18. Each subject will receive two PET scans per day on two separate days. Fifteen cocaine abusers and fifteen normal controls will be studied. Cocaine abusing subjects will be tested at two points during detoxification: during early withdrawal (1-2 weeks after last cocaine use) and two-six weeks later. This will allow the investigators to assess if the abnormal GABA responses are due to cocaine withdrawal and to assess if they recover with protracted detoxification. A potential side effect of radiation is the induction of cancer. However, no harm in a human individual or in a large population exposed at the doses as low as those delivered in this procedure (1100 mrem) has been reported. The estimation of risk of harm can be obtained only by extrapolation from much higher doses. Arterial catheterization has the following rare, but possible, complications: pain during the placement of the catheter, a risk of bleeding at the skin puncture site; the possibility of local infection, and temporary or permanent impairment of the blood supply to portions of the hand. Whenever blood is removed or a substance injected by venipuncture, there is minor discomfort and a slight possibility of local bleeding in the tissues. All records are confidential and may not be disclosed without the subject's written permission with the exception that the FDA and/or funding agencies may inspect the records. Documented informed consent is obtained from all subjects in a manner compliant with all federal regulations.
"PET Studies of the Relationship Between Dopamine Transporter Occupancy by Methylphenidate and Changes in Brain Dopamine"
Principal Investigator: Dr. Nora D. Volkow, Brookhaven National Laboratory
Project started in: 1999
Funding for Human Subjects Research: No Funding Sources Reported
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Brookhaven National Laboratory
Most recent approval: 11/08/00
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:
Dopamine is a neurotransmitter which is involved in movement, cognition and reward. Drugs of abuse like cocaine, as well as many therapeutic drugs like Ritalin (methylphenidate), bind to sites on dopamine nerve cells (called dopamine transporters, DAT) causing increases in brain dopamine. Because dopamine transporters serve to remove dopamine and terminate its action, when they are blocked by drugs like cocaine, an increase in dopamine occurs. The purpose of this study is to perform brain imaging studies with PET in order to better understand the relationship between DAT blockade by methylphenidate (MP) and changes in brain dopamine. PET will be used with [11C]cocaine to measure DAT blockade and with [11C]raclopride (a radioligand which competes with DA for binding to DA D2 receptors) to measure changes in synaptic DA induced by MP in normal subjects. In parallel, self reports of drug effects will be recorded to assess their relationship to the biochemical measures. Three experiments that compare the effects of intravenous and oral MP at different times of administration are planned. The first experiment will use PET five minutes after intravenous administration of MP and the second will use PET 60 minutes after intravenous administration of MP. Fifteen normal volunteers will be used in each experimental group. There will be no repeat studies.A potential side effect of radiation is the induction of cancer. However, no harm in a human individual or in a large population exposed at the doses as low as those delivered in this procedure (1248 mrem) has been reported. The estimation of risk of harm can be obtained only by extrapolation from much higher doses. Arterial catheterization has the following rare, but possible, complications: pain during the placement of the catheter, a risk of bleeding at the skin puncture site; the possibility of local infection, and temporary or permanent impairment of the blood supply to portions of the hand. Whenever blood is removed or a substance injected by venipuncture, there is minor discomfort and a slight possibility of local bleeding in the tissues. Methylphenidate is a mild central nervous system stimulant used to treat attention deficit disorder and narcolepsy. It increases heart rate and blood pressure and can cause a behavioral "high". It can also elicit negative feelings of anxiety. In the event that either cardiovascular or behavioral complications occur, they can be effectively treated with an intramuscular injection of a neuroleptic. Since methylphenidate will be administered orally, the likelihood of cardiac stimulation is lower. There is also some evidence that methylphenidate may lower the seizure threshold in some individuals who have a prior history of seizure disorders. Therefore, methylphenidate will not be given to patients with cardiac disease or patients with seizure disorders. All records are confidential and may not be disclosed without the subject's written permission with the exception that the FDA and/or funding agencies may inspect the records. Documented informed consent is obtained from all subjects in a manner compliant with all federal regulations.
"Evaluation of Cerebral Blood Vessel Function in Drug Abusers"
Principal Investigator: Dr. Jing Huei Lee, Brookhaven National Laboratory
Project started in: 1999
This project ended in fiscal year 2001.
Funding for Human Subjects Research: No Funding Sources Reported
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Brookhaven National Laboratory
Most recent approval: 01/04/00
Explanation of IRB approval:
Protocol was inactivated by PI 11/00
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: 01/04/00 to 10/01/00
Explanation:
Protocol was inactivated 10/00
Type(s) of Human Subjects Involvement:
The principal goal is a quantatively comparative analysis of regional brain activation using functional magnetic resonance imaging (fMRI) between normal subjects and age/gender matched cocaine users. The purpose of this study is to 1) develop a new technique which reveals a functional change in brain neurophysiology; and 2) compare those activation areas between a normal control group and an age/gender matched group of chronic cocaine users. If those differences are statistically significant, it will provide a tool for document of a sub-clinical neurophysiologic change related to substance (cocaine) use. Ten normal controls and ten chronic cocaine users will undergo quantitative measures of fMRI signals associated with brain activities by using magnetic resonance imaging at 4T. Subjects will have their visual cortex stimulated by using goggles with implanted Light Emitting Diodes (LEDs) that can pulse at a variety of frequencies. No contrast agents, drugs, diets or sleep deprivation will be used in this study. The total duration of the fMRI measurement will be two hours or less. All records are confidential and may not be disclosed without the subject's written permission with the exception that the FDA and/or funding agencies may inspect the records. Documented informed consent is obtained from all subjects in a manner compliant with all federal regulations.
"Magnetic Field Dependence of Water Proton Relaxation in Human Brain"
Principal Investigator: Dr. William Rooney, Brookhaven National Laboratory
Project started in: 1999
Funding for Human Subjects Research: No Funding Sources Reported
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Brookhaven National Laboratory
Most recent approval: 03/30/01
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Year prior to last IRB approval date
Type(s) of Human Subjects Involvement:
This application proposes the study of the magnetic field dependence of T1 relaxation times of brain water protons. T1 is an NMR relaxation time that characterizes how rapidly a sample becomes magnetized after being placed in a strong magnetic field. In protein solutions, water proton T1 values increase with increasing magnetic field strengths. The functional dependence of how the T1 relaxation times change with increasing magnetic field contains a wealth of information on the underlying water molecular interactions at the protein surface. For example, the magnetic field dependence of T1 has been used to estimate the time a water molecule resides at a protein surface site and how many of these water binding sites are present for a given protein. This technique has been referred to as relaxometry, and it has been applied to study 1H2O relaxation of many protein solutions and excised tissues. However, one of the physical properties most difficult to mimic accurately, and most sensitive to tissue state, is the NMR relaxation time. The advent of high-field MRI scanners provides the opportunity to obtain relaxation times from static magnetic fields that differ by nearly a factor of one-hundred. We propose the study of five healthy individuals, all experienced in MRI research, at magnet field strengths of 0.2T, 1.0T, 1.5T, 4.0T, and 7.0T. These MRI scanners are located at different institutions. The duration of each magnetic resonance study will be two hours or less. All MRI scans for a given subject will be completed within three months. The goal of this project is to gain a better understanding of how water interacts with proteins and membranes in living brain tissue. This information is of fundamental importance, not only in the basic science area of water molecular dynamics in tissue, but also in optimizing MRI tissue contrast and in improving MRI sensitivity for disease detection. All records are confidential and may not be disclosed without the subject's written permission with the exception that the FDA and/or funding agencies may inspect the records. Documented informed consent is obtained from all subjects in a manner compliant with all federal regulations.
"Mechanisms of Fat Induced Insulin Resistance"
Principal Investigator: Dr. JingHuei Lee, Brookhaven National Laboratory
Project started in: 1999
This project ended in fiscal year 2001.
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Brookhaven National Laboratory
Most recent approval: 05/02/00
Explanation of IRB approval:
Protocol was inactivated by PI 02/01
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 6
Reporting period for number of human subjects:
Other: 05/02/00 to 02/01/01
Explanation:
Project was inactivated 02/01
Type(s) of Human Subjects Involvement:
This study is designed to examine the interaction between metabolism of fat and sugar in the body. The body stores fat not only in fat cells, but can also store it to a degree in muscle tissue, where the body uses it as food. This study is done to better understand the way fat is built up and degraded in muscle cells in relationship to blood sugar. To prepare for the study, subjects will consume a high carbohydrate diet for three days. They will then be intermittently studied using magnetic resonance scans at the High Field MR laboratory at BNL over a period of 36 hours during which time they will be fasting. Sixteen normal volunteers will participate in this study.
The possible risks of placing an intravenous catheter in the vein include: the occurrence of discomfort and/or bruising at the site of puncture, occasional fainting, and less commonly infection, the formation of a small blood clot, bleeding at the needle puncture site, or swelling of the vein and surrounding tissue. Fasting for 36 hours is not dangerous for someone in good health. Occasionally some people may feel a little light-headed, although most people report they have increased energy and are more alert. The investigators have studied volunteers over 20 times fasting for this time period without any ill effects. With the type of magnet used in this study, no x-rays or similar level radiation will be used. No radioactive materials are used in this study. Reported physical discomforts have included claustrophobia (resulting from lying in an enclosed space), mild vertigo and very sporadically, metallic taste. Aside from the claustrophobia, all of these effects are transient and will resolve in under 1-2 minutes after lying still in the magnet. As in all MR studies (clinical and research), the side effect from using radiofrequency waves is similar to that of using cell phones or watching TV, which is a slight warming sensation. This is nearly always imperceptible, the level at which we work being always lower than is permitted by the FDA. Other than these possible sensations, the need to remain still and an intermittent loud noise, there are no other physical discomforts with the test. There are other possible risks to the procedure such as temporary numbness, but these are rare. Although the long term risk of exposure is not known, the possibility of any long-term risk is extremely low in view of the information accumulated over the past 20 years at lower magnet strengths and 7 years at this magnet strength. All records are confidential and may not be disclosed without the subject's written permission with the exception that the FDA and/or funding agencies may inspect the records. Documented informed consent is obtained from all subjects in a manner compliant with all federal regulations.
"PET Studies of Alcoholism: Measurement of the Effect of Alcohol Intoxication on Brain Glucose Metabolism"
Principal Investigator: Dr. Nora D. Volkow, Brookhaven National Laboratory
Project started in: 1999
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Brookhaven National Laboratory
Most recent approval: 03/27/01
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 6
Reporting period for number of human subjects:
Other: 04/04/00 to 02/12/01
Explanation:
We enrolled 6 subjects.
Type(s) of Human Subjects Involvement:
This study will measure the acute effects of alcohol on brain glucose metabolism in normal subjects. Twenty normal controls (male and female) will be recruited. Each subject will undergo 2-3 Positron Emission Tomography (PET), a type of imaging device, scans with 4.5 millicuries (mCi) of 18-fluorodeoxyglucose (18FDG), a radioactive analog of glucose (sugar), to estimate glucose metabolism in various parts of the brain. One of the scans will be done with a placebo (diet soda), and the other two will be done after administration of alcohol (0.75 grams per kilogram body weight (g/kg) and either 0.25 or 0.5 g/kg). The study will take 2-3 days. A potential side effect of radiation is the induction of cancer. However, no harm in a human individual or in a large population exposed at the doses as low as those delivered in this procedure (1485 mrem) has been reported. The estimation of risk of harm can be obtained only by extrapolation from much higher doses. Arterial catheterization has the following rare, but possible, complications: pain during the placement of the catheter, a risk of bleeding at the skin puncture site, the possibility of local infection, and temporary or permanent impairment of the blood supply to portions of the hand. Whenever blood is removed or a substance injected by venipuncture, there is minor discomfort and a slight possibility of local bleeding in the tissues. Alcohol impairs motor coordination and subjects should not drive or perform any activity that requires motor skills on the day of the study. It can also cause nausea and/or vomiting. Also, the use of alcohol with other drugs may be dangerous. All records are confidential and may not be disclosed without the subject's written permission with the exception that the FDA and/or funding agencies may inspect the records. Documented informed consent is obtained from all subjects in a manner compliant with all federal regulations.
"MR Investigation of Brain Metabolism in Fasting and Ketosis Using Beta-Hydroxybutyrate Infusions"
Principal Investigator: Dr. Manoj K. Sammi, Brookhaven National Laboratory
Project started in: 1999
This project ended in fiscal year 2001.
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Brookhaven National Laboratory
Most recent approval: 08/01/00
Explanation of IRB approval:
Protocol was inactivated by PI 03/01
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 6
Reporting period for number of human subjects:
Other: 08/01/00 to 03/01/01
Explanation:
protocol was inactivated 03/01
Type(s) of Human Subjects Involvement:
This study focuses on understanding how the brain accumulates and uses ketones under conditions of a three day fast. Ketones are the natural substitute for sugar when sugar is in short supply, as it is under fasting conditions. The study uses high field magnetic resonance (MR) spectroscopy and imaging to perform these measurements. The ketones will be measured under four conditions: baseline (non-fasting); baseline with ketone infusion; during the fast; and during the fast with ketone infusion. The study is a collaboration between the Albert Einstein College of Medicine General Clinical Research Center (AECOM GCRC) and the Brookhaven National Laboratory Magnetic Resonance Imager (BNL MRI). Subjects will be housed at the AECOM GCRC during the fast and will be transported to the BNL MRI for measurements. Twenty-four normal, healthy volunteers will be studied each year for two years. Each volunteer will undergo five series of MR images over a four week period. The fasting period is for three days, and the non-fasting imaging is performed within four weeks of the fasting study. The risk of participating in the fasting component of this study is primarily that of dehydration and low blood sugar. The risk of the Beta-Hydroxybutyrate (BHB) infusion is primarily due to the volume that is infused. Thus, monitoring of heart rate, breathing and blood pressure will be performed throughout all the MR studies. Certain complications can occur with placement of the intravenous catheter, primarily bleeding and clotting at the entry site. These are transient and will resolve. On rare occasions, inflammation of the vein may occur or a bruise may occur over the puncture site. Such problems usually subside by themselves. With the type of magnet used in this study, no x-rays or similar level radiation will be used. No radioactive materials are used in this study. Reported physical discomforts have included claustrophobia (resulting from lying in an enclosed space), mild vertigo and a very sporadic, metallic taste. Aside from the claustrophobia, all of these effects are transient and will resolve in under 1-2 minutes after lying still in the magnet. As in all MR studies (clinical and research), the side effect from using radiofrequency waves is similar to that of using cell phones or watching TV, which is a slight warming sensation. This is nearly always imperceptible, the level at which we work being always lower than is permitted by the FDA. Other than these possible sensations, the need to remain still and an intermittent loud noise, there are no other physical discomforts with the test. There are other possible risks to the procedure such as temporary numbness, but these are rare. Although the long term risk of exposure is not known, the possibility of any long-term risk is extremely low in view of the information accumulated over the past 20 years at lower magnet strengths and 7 years at this magnet strength. All records are confidential and may not be disclosed without the subject's written permission with the exception that the FDA and/or funding agencies may inspect the records. Documented informed consent is obtained from all subjects in a manner compliant with all federal regulations.
"MR Spectroscopy to Monitor HAART in HIV Brain Injury/MRS to Monitor HAART in HIV+ Methamphetamine Users"
Principal Investigator: Dr. Linda Chang, Brookhaven National Laboratory
Project started in: 1999
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Brookhaven National Laboratory
Most recent approval: 12/05/00
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: 12/05/00 to 10/01/01
Explanation:
Project started 12/00
Type(s) of Human Subjects Involvement:
The purpose of this study is to find out whether a new brain scanning technique, magnetic resonance spectroscopy (MRS), can be used to determine whether a combination of medications can change the brain chemicals in patients with HIV who have not been previously treated with any medications for their HIV infection. In addition, patients who have a history of methamphetamine dependence and have not been previously treated for HIV will also be studied, allowing MRS to identify the severity of brain injury due to HIV, methamphetamine use, or both. Subjects will be asked to undergo a brain scan known as magnetic resonance imaging/magnetic resonance spectroscopy (MRI/MRS) which uses a strong magnet and radio waves to generate signals that indicate the amounts of a variety of important chemicals in the body. Subjects will also be given a series of neuropsychological tests that examine the subject's psychomotor speed, fine and gross motor functioning, and various cognitive function. The subject population for this study will include 60 subjects with HIV-CMC (HIV-cognitive motor complex) who have not been previously treated with antiretroviral drugs, 20 seronegative healthy drug-free control subjects, and 45 subjects with HIV-CMC and a history of methamphetamine dependence who have not been previously treated with antiretroviral drugs. We expect to study 125 subjects over the next two years. Due to the gender distribution of the disease (HIV), approximately 75% of this total will be male and approximately 25% will be female. Those subjects with HIV-CMC only, will repeat the study at 3, 6, and 9 months after initial evaluation. Those subjects with HIV-CMC and who have a history of methamphetamine dependence, will repeat the study 3 months after initial evaluation. Healthy control subjects will not repeat the study. The major risk of the spinal tap is pain on the back where the spinal tap was done. Some individuals develop a headache that can last for days; prolonged headache develops in only 1 in 50 to 1 in 200 subjects. This headache is usually relieved with Tylenol (acetaminophen), drinking a lot of fluids and lying flat. A persistent headache may result from continued spinal fluid leakage. The effects of inserting needles to draw blood are usually some pain, bleeding and/or a bruise or swelling where the needle was inserted and on rare occasions, infection. Occasionally the area around the vein may swell. Any area where the skin anesthetic will be applied may become red and/or irritated. The neuropsychological testing and evaluation may make subjects feel uncomfortable.
All records are confidential and may not be disclosed without the subject's written permission, except that the FDA and/or funding agencies may inspect the records.
"Monitoring Methamphetamine Abuse Treatment with 1H MRS"
Principal Investigator: Dr. Linda Chang, Brookhaven National Laboratory
Project started in: 1999
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Brookhaven National Laboratory
Most recent approval: 12/05/00
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 25
Reporting period for number of human subjects:
Other: 12/05/00 to 10/01/01
Explanation:
Project started 12/00
Type(s) of Human Subjects Involvement:
The purpose of this study is to find out whether people who were dependent on methamphetamine have abnormal brain chemistry or abnormal thinking and memory, and to determine whether behavioral treatment for methamphetamine-dependence is associated with improvement of brain chemicals and thinking processes. Also, the study will determine whether magnetic resonance spectroscopy (MRS) can be used as a tool to predict the length of time to relapse. Subjects will be asked to undergo a brain scan known as magnetic resonance imaging/magnetic resonance spectroscopy (MRI/MRS) which uses a strong magnet and radio waves to generate signals that indicate the amounts of a variety of important chemicals in the body. Subjects will also be given a series of neuropsychological tests that examine the subject's psychomotor speed, fine and gross motor functioning, and various cognitive function. The subject population for this study will include 75 subjects who have been dependent on methamphetamine and 30 healthy drug-free control subjects. We expect to study approximately equal numbers of male and female subjects over the next two years for a combined total of 105 subjects. All 75 subjects who have been dependent on methamphetamine will repeat the study at four months and nine months after initial evaluation. The effects of inserting needles to draw blood are usually some pain, bleeding and/or a bruise or swelling where the needle was inserted and on rare occasions, infection. Occasionally the area around the vein may swell. Any area where the skin anesthetic will be applied may become red and/or irritated. The neuropsychological testing and evaluation may make subjects feel uncomfortable.
All records are confidential and may not be disclosed without the subject's written permission, except that the FDA and/or funding agencies may inspect the records.
"Brain Activation Studies in Patients with Early HIV Dementia"
Principal Investigator: Dr. Thomas Ernst, Brookhaven National Laboratory
Project started in: 1999
Funding for Human Subjects Research: No Funding Sources Reported
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Brookhaven National Laboratory
Most recent approval: 12/05/00
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: 12/05/00 to 10/01/01
Explanation:
Project started 12/00
Type(s) of Human Subjects Involvement:
The purpose of this research is to determine the effects of the human immunodeficiency virus (HIV) on the mental processing (functioning of the brain) in AIDS patients, using several magnetic resonance imaging (MRI) techniques. Brain function will be examined using a technique called functional MRI (fMRI). The study will observe the response of the brain to different functions (such as seeing, remembering, or moving body parts). In addition, a perfusion magnetic resonance imaging (pMRI) scan will be done to observe blood flow in the brain. This research study will enroll subjects who are HIV-positive and subjects who are HIV-negative and are healthy. Subjects will also be given a series of neuropsychological tests that examine the subject's psychomotor speed, fine and gross motor functioning, and various cognitive function. The subject population for this study will include 20 early HIV-CMC (HIV-cognitive motor complex; ADC stages 0.5 and 1) subjects, 20 HIV subjects without cognitive deficits (ADC stage 0), 20 subjects with HIV-CMC (ADC stages 0.5 and 1) who have never been treated with antiretroviral drugs, and 20 healthy control subjects. We expect to study 80 subjects over the next two years. Due to the gender distribution of the disease (HIV) approximately 75% of the total subjects studied will be male and approximately 25% will be female. Only 40 subjects (antiretroviral drug naive subjects) will repeat the study 3 three months after initial evaluation. The major risk of the spinal tap is pain on the back where the spinal tap was done. Some individuals develop a headache that can last for days; prolonged headache develops in only 1 in 50 to 1 in 200 subjects. This headache is usually relieved with Tylenol (acetaminophen), drinking a lot of fluids and lying flat. A persistent headache may result from continued spinal fluid leakage. The effects of inserting needles to draw blood are usually some pain, bleeding and/or a bruise or swelling where the needle was inserted and on rare occasions, infection. Occasionally the area around the vein may swell. Any area where the skin anesthetic will be applied may become red and/or irritated. The neuropsychological testing and evaluation may make subjects feel uncomfortable. The risks of a gadolinium injection include discomfort and bruising at the site of puncture and, less commonly, the formation of a small blood clot or swelling of the vein and nearby tissue and bleeding from the puncture site. A small number of people have had bad reactions to the gadolinium contrast agent solution. Some of the bad reactions include headache, dizziness, metallic taste in mouth, nausea, and rash or hives. Death has been reported due to severe allergic reactions, but this has been an extremely rare occurrence with an estimated risk of 1 in 500,000.
All records are confidential and may not be disclosed without the subject's written permission, except that the FDA and/or funding agencies may inspect the records.
"Simultaneous Functional Magnetic Resonance Imaging and Event-Related Potential Recording"
Principal Investigator: Dr. Jing-Huei Lee, Brookhaven National Laboratory
Project started in: 2000
Funding for Human Subjects Research: No Funding Sources Reported
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Brookhaven National Laboratory
Most recent approval: 09/05/00
Explanation of IRB approval:
Protocol was inactivated at its annual review
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 goal of this study is to evaluate human brain function associated with behavioral and cognitive activities by simultaneous functional Magnetic Resonance Imaging (fMRI) and electroencephalographic (EEG) recordings, and to conduct research aimed at increasing the investigators understanding of the mechanisms and evolution of normal brain function and human diseased states. The success of this work will not only provide information on the fundamental mechanism underlying fMRI, but also open a possibility of mapping brain function with high temporal and spatial resolution. The human brain mapping will be obtained simultaneously using 4-Tesla magnetic resonance imaging and 64-channel EEG recordings with presentations of auditory and visual stimuli to subjects in the scanner. No radiopharmacueticals, drugs or surgical procedures will be used in this study. The total duration of each fMRI and EEG study will be two hours or less. One hundred studies of normal, health volunteers, aged 18-90, are expected to be performed each year.
The study is considered to involve minimal risk. No serious ill effects have been reported to date from any site operating with 4T magnetic field strength. Because of the strong magnetic field, however, subjects will be screened for the presence of any surgically implanted metallic devices such a clips, artificial joints, heart valves and pacemakers. Since the study involves entering a confining space (the magnet), subjects may not be able to participate if they have a history of claustrophobia, or if they experience anxiousness when entering the magnet. The risks due to the magnet are primarily related to the slight possibility of a sensation of dizziness or nausea as subjects move into and out of the magnet, or move their head within the magnet.
All records are confidential and may not be disclosed without the subject's written permission with the exception that the FDA and/or funding agencies may inspect the records. Documented informed consent is obtained from all subjects in a manner compliant with all federal regulations.
"PET Studies of Catechol-O-Methyltransferase (COMT) with [18F]Ro-41-0960"
Principal Investigator: Dr. YuShin Ding, Brookhaven National Laboratory
Project started in: 2000
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Brookhaven National Laboratory
Most recent approval: 04/17/01
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Year prior to last IRB approval date
Type(s) of Human Subjects Involvement:
COMT (catechol-O-methyltransferase) is a natural enzyme in the body that is sometimes found in greater amounts in certain breast tumors. The purpose of this study is to determine whether the larger amounts of COMT can be seen in breast cancer with Positron Emission Tomography (PET), a medical imaging method similar to a camera, and whether this information can be of value in breast cancer diagnosis and treatment. The procedure will involve PET scanning with a tracer called [18F]Ro41-0960, which links itself with the COMT already in the tumor. Subjects with breast cancer who are scheduled to undergo surgery will have a PET scan within two weeks preceding the surgery. The results of the PET scan will be compared with the results obtained by examination of the surgical sample, which is removed during the surgery. If PET and the experimental tracer [18F]Ro41-0960 provide diagnostic information, it could reduce the need for unnecessary breast biopsies and make current diagnostic procedures better. This study may also provide knowledge which may suggest new treatments for breast cancer. Twenty breast cancer patients will be studied up to two times each.
A potential side effect of radiation is the induction of cancer. However, no harm in a human individual or in a large population exposed at doses as low as that delivered in this procedure has been reported. The estimation of risk of harm can be obtained only by extrapolation from much higher doses. Arterial catheterization has the following rare, but possible, complications: pain during the placement of the catheter, a risk of bleeding at the skin puncture site, the possibility of local infection, and temporary or permanent impairment of the blood supply to portions of the hand. Whenever blood is removed or a substance injected by venipuncture, there is minor discomfort and a slight possibility of local bleeding in the tissues. Arterial catheterization has the following rare, but possible, complications: pain during the placement of the catheter, a risk of bleeding at the skin puncture site; the possibility of local infection, and temporary or permanent impairment of the blood supply to portions of the hand. Whenever blood is removed or a substance injected by venipuncture, there is minor discomfort and a slight possibility of local bleeding in the tissues.
All records are confidential and may not be disclosed without the subject's written permission with the exception that the FDA and/or funding agencies may inspect the records. Documented informed consent is obtained from all subjects in a manner compliant with all federal regulations.
"PET Studies of Monoamine Oxidse (MAO)"
Principal Investigator: Dr. Joanna S. Fowler, Brookhaven National Laboratory
Project started in: 2000
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Brookhaven National Laboratory
Most recent approval: 11/08/00
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 12
Reporting period for number of human subjects:
Other: 11/08/00 to 09/24/01
Explanation:
Protocol began 12/99.
Type(s) of Human Subjects Involvement:
We propose to develop methods to image the enzyme monoamine oxidase (MAO) in the human body. This is an important baseline study which will allow future studies to assess the potential effect of drugs, foods or other exposures inhibit MAO. Drug studies, however, are not a part of this proposal. MAO breaks down neurotransmitter amines and vasoactive chemical compounds present in certain fermented foods, drugs and beverages. If MAO is inhibited, the individual is at risk for dangerous elevations in blood pressure. Therefore a knowledge of the effect of drugs and other substances on MAO is important. PET imaging will allow this assessment to be made directly in the human body. MAO exists in two subtypes, MAO A and MAO B which differ in their selectivity for breaking down different chemical compounds.
We propose to study 36 subjects in 2 years. We will measure MAO A and/or MAO B in each subject. MAO A will be measured using [11C]clorgyline and [11C]clorgyline-D2 (deuterium substituted [11C]clorgyline) and MAO B will be measured using [11C]L-deprenyl and [11C]L-deprenyl-D2 (deuterium substituted [11C]L-deprenyl). Volunteers may participate in either or both of these studies. If they participate in one of the studies they will receive two PET scans and if they participate in both of the studies, they will receive four PET scans.
A potential side effect of radiation is the induction of cancer.
However, no harm in a human individual or in a large population exposed at doses as low as that delivered in this procedure has been reported. The estimation of risk of harm can be obtained only by extrapolation from much higher doses. Arterial catheterization has the following rare, but possible, complications: pain during the placement of the catheter, a risk of bleeding at the skin puncture site, the possibility of local infection, and temporary or permanent impairment of the blood supply to portions of the hand. Whenever blood is removed or a substance injected by venipuncture, there is minor discomfort and a slight possibility of local bleeding in the tissues. Arterial catheterization has the following rare, but possible, complications: pain during the placement of the catheter, a risk of bleeding at the skin puncture site; the possibility of local infection, and temporary or permanent impairment of the blood supply to portions of the hand. Whenever blood is removed or a substance injected by venipuncture, there is minor discomfort and a slight possibility of local bleeding in the tissues.
All records are confidential and may not be disclosed without the subject's written permission with the exception that the FDA and/or funding agencies may inspect the records. Documented informed consent is obtained from all subjects in a manner compliant with all federal regulations.
"Brain Dopamine and Reward and Motivation in Controls and Substance Abusers"
Principal Investigator: Dr. Nora D. Volkow, Brookhaven National Laboratory
Project started in: 2000
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Brookhaven National Laboratory
Most recent approval: 03/27/01
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 12
Reporting period for number of human subjects:
Other: 05/02/00 to 03/05/01
Explanation:
We reported the period 5/02/00 to 3/05/01 because this is the last period of recertification for this protocol.
Type(s) of Human Subjects Involvement:
The purpose of this study is: (Study # 1) to assess the involvement of dopamine (DA) in motivation and reinforcing behavior in humans and (Study #2) to compare the level of activation of reward circuits in normal controls with that of cocaine abusers. We predict that (1) DA in humans subjects will be involved with reward and motivational circuits and (2) cocaine abusers will have decreased activation of reward circuits by naturally rewarding stimuli when compared with controls but they will have very robust responses to drug related stimuli.
Number of Subjects:
Study # 1: 5 normal controls (4 scans each with [11C]raclopride; two on each day) with different stimuli, 10 cocaine abusers and 10 normal controls (4 scans each with [11C]raclopride; two on each day) with cocaine video stimulation.
Study 2: 20 controls and 20 cocaine abusers will have four [11C]raclopride scans to assess the effects of naturally rewarding stimuli.
A potential side effect of radiation is the induction of cancer. However, no harm in a human individual or in a large population exposed at doses as low as that delivered in this procedure has been reported. The estimation of risk of harm can be obtained only by extrapolation from much higher doses. Arterial catheterization has the following rare, but possible, complications: pain during the placement of the catheter, a risk of bleeding at the skin puncture site, the possibility of local infection, and temporary or permanent impairment of the blood supply to portions of the hand. Whenever blood is removed or a substance injected by venipuncture, there is minor discomfort and a slight possibility of local bleeding in the tissues. Arterial catheterization has the following rare, but possible, complications: pain during the placement of the catheter, a risk of bleeding at the skin puncture site; the possibility of local infection, and temporary or permanent impairment of the blood supply to portions of the hand. Whenever blood is removed or a substance injected by venipuncture, there is minor discomfort and a slight possibility of local bleeding in the tissues. Methylphenidate is a mild central nervous system stimulant used to treat attention deficit disorder and narcolepsy. It increases heart rate and blood pressure and can cause a behavioral "high". It can also elicit negative feelings of anxiety. There is also some evidence that methylphenidate may lower the seizure threshold in some individuals who have a prior history of seizure disorders.
All records are confidential and may not be disclosed without the subject's written permission with the exception that the FDA and/or funding agencies may inspect the records. Documented informed consent is obtained from all subjects in a manner compliant with all federal regulations.
"Follow-Up Protocol for the Boron Neutron Capture Therapy Clinical Trial at Brookhaven National Laboratory"
Principal Investigator: Dr. Jeffrey A. Coderre, Brookhaven National Laboratory
Project started in: 2000
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Brookhaven National Laboratory
Most recent approval: 01/02/01
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 4
Reporting period for number of human subjects:
Year prior to last IRB approval date
Type(s) of Human Subjects Involvement:
This protocol will unify the follow-up and improve data collection of subjects treated under the Boron Neutron Capture Therapy protocols at Brookhaven National Laboratory. Follow-up histories, physicals and clinical laboratory tests will be performed at the following times post-BNCT: Quarterly for the first year after BNCT; and every six months thereafter. Follow-up brain scans will be done at the following times post-BNCT by the referring or follow-up physician: Quarterly for the first year after BNCT; and every six months thereafter. The patients will be invited to BNL for follow-up with the participating physicians at BNL biannually. MRIs and/or CTs will not be performed at BNL. Whenever blood is removed or a substance injected by venipuncture, there is minor discomfort and a slight possibility of local bleeding in the tissues. All records are confidential and may not be disclosed without the subject's written permission with the exception that the FDA and/or funding agencies may inspect the records. Documented informed consent is obtained from all subjects in a manner compliant with all federal regulations.
"Perception of Pleasure and Control of Behavior in Drug Addiction: An fMRI Study"
Principal Investigator: Dr. Rita Goldstein, Brookhaven National Laboratory
Project started in: 2000