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: 47
| BNL-96-265 | "General Magnetic Resonance Imaging (MRI) and Spectroscopic (MRS) Studies of Human Subjects" |
| BNL-98-296 | "Brain Water Content and Blood-Brain Barrier Permeability in Multiple Sclerosis" |
| BNL-99-301 | "PET Studies of Alcoholism: Measurement of Brain Glucose Metabolism and Dopamine Activity in Alcoholics During Early and Late Detoxification" |
| BNL-99-302 | "PET Studies of Alcoholism: Measurement of Brain Metabolism and Brain Dopamine Concentration with 18FDG and 11C-Raclopride" |
| BNL-99-306 | "PET Studies of the Relationship Between Dopamine Transporter Occupancy by Methylphenidate and Changes in Brain Dopamine" |
| BNL-99-312 | "Magnetic Field Dependence of Water Proton Relaxation in Human Brain" |
| BNL-99-317 | "PET Studies of Alcoholism: Measurement of the Effect of Alcohol Intoxication on Brain Glucose Metabolism" |
| BNL-99-347 | "MR Spectroscopy to Monitor HAART in HIV Brain Injury/MRS to Monitor HAART in HIV+ Methamphetamine Users" |
| BNL-99-348 | "Monitoring Methamphetamine Abuse Treatment with 1H MRS" |
| BNL-99-349 | "Brain Activation Studies in Patients with Early HIV Dementia" |
| BNL-00-324 | "PET Studies of Catechol-O-Methyltransferase (COMT) with [18F]Ro-41-0960" |
| BNL-00-325 | "PET Studies of Monoamine Oxidase (MAO)" |
| BNL-00-326 | "Brain Dopamine and Reward and Motivation in Controls and Substance Abusers" |
| BNL-00-327 | "Follow-Up Protocol for the Boron Neutron Capture Therapy Clinical Trial at Brookhaven National Laboratory" |
| BNL-00-328 | "Perception of Pleasure and Control of Behavior in Drug Addiction: An fMRI Study" |
| BNL-00-329 | "MR Spectroscopic Imaging of Multiple Sclerosis: Effects of Donzepil Therapy in a Double Blinded Trial" |
| BNL-00-340 | "Follow-Up Study of Alcohol and Cocaine Abusers, Comparing Addiction History and Dopamine Receptor Density" |
| BNL-00-341 | "PET Studies in Cocaine Abusers: Effects of Deprenyl" |
| BNL-00-344 | "Blood Brain Barrier Permeability and the Menstrual Cycle" |
| BNL-01-345 | "Brain Imaging Studies of Obesity" |
| BNL-01-346 | "PET Studies of Monoamine Oxidase (MAO) and Brain Glucose Metabolism in Alzheimer's Disease" |
| BNL-01-350 | "PET Imaging Studies of Brain Dopamine: Changes in Subjects Infected with Human Immunodeficiency Virus (HIV)" |
| BNL-01-351 | "Effects of Estrogen Replacement on Brain Dopamine Function" |
| BNL-01-352 | "PET Studies of Cocaine Abuse: Effects of Expectation" |
| BNL-01-353 | "PET Studies in Attention Deficit Disorder: Role of Dopamine" |
| BNL-01-354 | "Medical Surveillance of former BNL Employees Identified as Beryllium Exposed" |
| BNL-01-355 | "Blood Brain Barrier Permeability in MS Lesion Development" |
| BNL-01-356 | "Oral Methylphenidate: Effects on Human Heart" |
| BNL-01-357 | "Magnetization Transfer Imaging and MR Spectroscopy in Elderly Schizophrenics" |
| BNL-01-358 | "Effect of Deep Space Radiation on Human Hematopoietic Stem Cells" |
| BNL-01-359 | "Cerebrovascular Changes in HIV and Psychostimulant Drug Abuse" |
| BNL-01-360 | "Attentional Modulation in Early Sensory Processing" |
| BNL-01-361 | "fMRI and pMRI Characteristics in Cocaine Use" |
| BNL-01-362 | "Investigation of the "Early Response" in Functional MRI" |
| BNL-01-363 | "Precise In Vivo Measurement of Brain Metabolites" |
| BNL-02-364 | "Brain Dopamine, Reward and Motivation in Obese Subjects With and Without a Binge Eating Disorder" |
| BNL-02-365 | "Imaging of Neuroendocrine Tumors Using PET (COMT)" |
| BNL-02-366 | "Water Spaces in Leg Muscle Before and After Exercise" |
| BNL-02-367 | "Heavy Ion Induced Chromosome Damage and Biomedical Countermeasures" |
| BNL-02-368 | "Effects of the Shielding on the Biological Effectiveness of Heavy Ions" |
| BNL-02-369 | "Clinical Correlates of Longitudinal Changes in Alzheimers Disease: A Glucose Challenge Study" |
| BNL-02-370 | "Imaging of Brain Metabolic Responses to Food Presentation" |
| BNL-02-371 | "Botulinum Toxoid" |
| BNL-02-372 | "Characterization of Dopamine Transporter Blockade by GW353162 in Human Brain" |
| BNL-02-373 | "Methamphetamine Effects in Brain Dopamine Activity" |
| BNL-02-374 | "Clinical Correlates of Longitudinal PET Changes in Normal Aging, Mild Cognitive Impairment and Alzheimer's Disease " |
| BNL-02-377 | "Proton Magnetic Resonance Spectroscopy (1H MRS) in Schizophrenia (Project 5 of Conte Center Grant through Mt. Sinai Medical Center)" |
"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: 05/28/02
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:
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.
"Brain Water Content and Blood-Brain Barrier Permeability in Multiple Sclerosis"
Principal Investigator: Dr. William Rooney, Brookhaven National Laboratory
Project started in: 1998
This project ended in fiscal year 2002.
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: 07/24/01
Explanation of IRB approval:
Protocol was inactivated by PI at continuing review 05/02
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Other: 07/24/01 to 05/13/02
Explanation:
Protocol was inactivated by PI at continuing review 05/02
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: 05/28/02
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:
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: 06/25/02
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 3
Reporting period for number of human subjects:
Year prior to last IRB approval date
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 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: 09/27/02
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
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 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.
"Magnetic Field Dependence of Water Proton Relaxation in Human Brain"
Principal Investigator: Dr. William Rooney, Brookhaven National Laboratory
Project started in: 1999
This project ended in fiscal year 2002.
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
Explanation of IRB approval:
Protocol was inactivated by PI 10/01
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: 03/20/01 to 10/25/01
Explanation:
Protocol was inactivated by PI 10/01
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.
"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: 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: 02/26/02
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Year prior to last IRB approval date
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 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 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: 11/27/01
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 3
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 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: 11/27/01
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 20
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 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:
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: 11/27/01
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 37
Reporting period for number of human subjects:
Year prior to last IRB approval date
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.
"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: 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: 03/28/02
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
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 Oxidase (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: 09/17/02
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 5
Reporting period for number of human subjects:
Year prior to last IRB approval date
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: 02/26/02
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:
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
This project ended in fiscal year 2002.
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
Explanation of IRB approval:
Protocol was inactivated by PI at continuing review 10/01
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 4
Reporting period for number of human subjects:
Other: 01/02/01 to 09/13/01
Explanation:
Protocol was inactivated by PI at continuing review 10/01
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
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: 04/23/02
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 13
Reporting period for number of human subjects:
Year prior to last IRB approval date
Type(s) of Human Subjects Involvement:
The goal of this application is to evaluate human brain function implicated in the perception of pleasure and control of behavior by simultaneous fMRI recordings and behavioral assessment. Specifically, this project will examine whether chronic use of cocaine and/or alcohol changes the pattern of this brain activity in such a way as to increase the uncontrollable use of these drugs. The results of this work will provide information on the brain circuits underlying drug-related behaviors, emotions and cognitions, which may then open a possibility of timely intervention and prevention of drug addiction. The human brain mapping will be obtained using a 4-Tesla magnetic resonance imaging scanner with presentations of visual and/or auditory stimuli to subjects in the scanner. No radiopharmacueticals, chemicals (drugs) or surgical procedures will be used in this study. The total duration of the fMRI study will be two hours or less. Subjects will include 20 normal controls, 20 cocaine abusers and 20 alcoholics.
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.
"MR Spectroscopic Imaging of Multiple Sclerosis: Effects of Donzepil Therapy in a Double Blinded Trial"
Principal Investigator: Dr. Manoj K. Sammi, Brookhaven National Laboratory
Project started in: 2000
This project ended in fiscal year 2002.
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: 03/27/01
Explanation of IRB approval:
Protocol was inactivated by PI at continuing review 10/01
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: 03/27/01 to 10/26/01
Explanation:
Protocol was inactivated by PI at continuing review 10/01
Type(s) of Human Subjects Involvement:
This study uses magnetic resonance (MR) spectroscopy to evaluate patients with multiple sclerosis (MS). Patients with MS frequently have thinking problems and may benefit from therapy with donepezil, an FDA approved medication being used to treat the cognitive symptoms of Alzheimers. Our previous work has shown that MR measurements of brain metabolism can be correlated to ability to perform on thinking tasks. Here, we will measure patients who are receiving either donepezil or placebo, versus controls. Thus in this study, the patients (n=22) will be studied twice by MR methods (before starting therapy and 6 months later) whereas the controls (n=22) will be studied once. We will determine whether those patients on donepezil demonstrate a MR spectroscopic difference compared to either control or to placebo.
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.
"Follow-Up Study of Alcohol and Cocaine Abusers, Comparing Addiction History and Dopamine Receptor Density"
Principal Investigator: Dr. Laurence Maynard, Brookhaven National Laboratory
Project started in: 2000
This project ended in fiscal year 2002.
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: 05/15/01
Explanation of IRB approval:
Protocol was inactivated by PI 10/01
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: 05/15/01 to 10/26/01
Explanation:
Protocol was inactivated by PI 10/01
Type(s) of Human Subjects Involvement:
We propose to contact cocaine and alcohol abusing subjects who underwent PET imaging at BNL during the years 1989-1996. We will compare the DA receptor density level, as it was measured then, with measures of addiction severity within the intervening years and to the approximate number of days they have been clean and times they have tried to detoxify. We hypothesize that subjects, who had low levels of DA D2 receptors, will be more severely addicted and will have a worse prognosis than those with higher receptors. For this purpose we will invite subjects back and after obtaining their informed consent and a diagnostic interview will be administered. To further corroborate history of recent drug abuse a urine sample will also be sent for toxicology screening. In an effort to corroborate those subjects who deny any recent drug use, we may also obtain a hair sample. This toxicological screen will give us evidence of either sobriety or drug abuse over the subjects past 3-6 months. 60 subjects are eligible. Of these, all that can be located and agree to participate in the study will participate. All subjects eligible will be tested as soon as they can be contacted and scheduled. There will be no repeat studies.
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 Cocaine Abusers: Effects of Deprenyl"
Principal Investigator: Dr. Nora D. Volkow, Brookhaven National Laboratory
Project started in: 2000
This project ended in fiscal year 2002.
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: 08/01/00
Explanation of IRB approval:
Protocol was inactivated 08/01/01
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: 08/01/00 to 08/01/01
Explanation:
Protocol was inactivated 08/01
Type(s) of Human Subjects Involvement:
Based on our PET studies showing that cocaine abusers have reduced brain dopamine activity, we will investigate whether treatment with Deprenyl can improve DA function. To do this, a PET camera will be used to visualize how much DA is released using [11C]raclopride, which is a radiochemical that attaches to the brain in proportion to the levels of DA receptors and to the concentration of DA. Because when DA is released in the brain it is immediately removed back into the cell we will need to block this removal, which we will do by treating subjects with methylphenidate (drug used in the treatment of Attention Deficit Disorder that blocks the transport of DA into the cell). The difference between the [11C]raclopride after placebo and that obtained after methylphenidate (MP) will reflect DA’s release. Subjects recruited for this study will be kept hospitalized in the inpatient research unit of the NIDA Addiction Research Center (Baltimore Maryland) for the duration of this study. We will study 40 cocaine abusers, which will be divided in two groups of 20 each; one to receive Deprenyl treatment and the other to receive placebo. Subjects will be tested on two different occasions before and after 3-4 weeks of treatment with either placebo or with Deprenyl (5 mg po twice a day). Each test will consist of two scans with [11C]raclopride; the first scan will be done after a placebo and the other will be done 2 hours later after MP.
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.
"Blood Brain Barrier Permeability and the Menstrual Cycle"
Principal Investigator: Dr. William Rooney, 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: 06/25/02
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 3
Reporting period for number of human subjects:
Year prior to last IRB approval date
Type(s) of Human Subjects Involvement:
One of the unique properties of brain blood vessels is the so-called "blood-brain barrier", which is important in brain volume regulation and in protecting brain cells from potentially toxic substances in the blood. Multiple sclerosis (MS) is a disease of unknown origin that produces lesions in the brain and spinal cord disease and it is believed that an initiating event in new lesion formation is the transient disruption of the blood-brain barrier. MS strikes women twice as often as men. Several studies have raised the possibility that menstrual cycle hormones influence MS disease activity, and could account for why women are at increased risk for the disease. The primary question that we address in this study is the extent to which the blood-brain barrier permeability changes with hormone levels that vary during the menstrual cycle. A secondary question is whether these changes are greater in women that have MS. Ten women between the ages of 18 and 40 years will be enrolled; five women with MS and five healthy women as controls. Dr. Patricia Coyle will recruit the MS candidates from the Multiple Sclerosis Comprehensive Care Center at the State University of New York at Stony Brook. All MS candidates will undergo an initial screening visit at Stony Brook. All enrolled participants will undergo a contrast enhanced MRI exam every week for four weeks at Brookhaven National Laboratory. Eight-ten teaspoons of blood will be withdrawn at each MRI examination to measure hormone and contrast agent levels. The contrast agent is an FDA approved compound that has an excellent safety profile. The high-field MRI scanner at Brookhaven National Laboratory will be used because it has a better ability to detect low levels of contrast agent than standard clinical scanners.
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. Whenever blood is removed or a substance injected by venipuncture, there is minor discomfort and a slight possibility of local bleeding in the tissues. 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 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 of Obesity"
Principal Investigator: Dr. Gene-Jack Wang, Brookhaven National Laboratory
Project started in: 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: 11/27/01
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 prevalence of obesity is increasing worldwide. The mechanisms leading to the loss of control of food intake are not understood. Dopamine (DA) is one of the neurotransmitters that involve in feeding behavior and its pharmacological manipulation has marked effects in food intake. Abnormal dopaminergic activity has been demonstrated in genetically inbred mice for obesity and has been postulated to underlie disorders entailing compulsive behaviors such as overeating. Our prior study showed that striatal DA D2 receptor availability was significantly lower in obese than in control subjects. It has been postulated that subjects who have low dopamine activity are more prone to self-administer food or reinforcing drugs as a way of compensating for the decreased dopaminergic activity. Animal studies indicate a decrease in body weight by dietary restriction increases DA D2 receptor concentration. Bariatric operations include procedures that decrease the volume capacitance of the stomach or establish a partial selective malabsorption are used to induce weight loss. These surgical procedures have been proven to be effective at inducing and maintaining a significant weight loss. The purpose of this study is to investigate if changes in the brain dopamine system of obese individuals revert to normal with surgically assisted weight loss. The study will evaluate 30 obese subjects (body mass index > 40 kg/m2) who are to undergo bariatric surgery and 30 control subjects in the age range 20-55 years of age. Obese subjects will be tested prior to and 6-12 months after surgery. Each evaluation will entail studies with 2 tracers, to measure postsynaptic DA sites ([11C]raclopride for dopamine D2 receptors) and to measure regional brain function (18F- fluorodeoxyglucose, for regional glucose metabolism). 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. 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. All records are confidential and may not be disclosed without the subject's written permission and except that the FDA and/or funding agencies may inspect the records.
"PET Studies of Monoamine Oxidase (MAO) and Brain Glucose Metabolism in Alzheimer's Disease"
Principal Investigator: Dr. Joanna S. Fowler, Brookhaven National Laboratory
Project started in: 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: 09/17/02
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 2
Reporting period for number of human subjects:
Year prior to last IRB approval date
Type(s) of Human Subjects Involvement:
In this study we propose to determine whether MAO B imaging with PET and [11C]L-deprenyl-D2 can be used to detect plaque formation in Alzheimer’s disease at very early stages and whether it tracks the progression of symptoms. Ultimately the goal is to have a marker which is predictive and which can be used to determine whether new therapies are effective against disease progression. We will recruit subjects with Alzheimer’s disease who are part of a longitudinal study (a study where the same subject is followed over time) at Mt. Sinai School of Medicine (MSSM) and a group of age-matched healthy subjects (including the spouses of the patients). There will be 16 subjects in each group. Each subject will receive a PET scan with [11C]L-deprenyl-D2 (to measure brain MAO B). If subjects agree, they may also have an 18FDG scan to measure brain function which will be of value in assessing whether regions with high MAO B also have diminished brain function. The scans may be repeated 12-24 months later (based on the assessment of the subject by the Mt. Sinai physician) to assess whether changes in the PET scans track the progression of symptoms. We have successfully used [11C]L-deprenyl-D2 to map MAO B in the normal human brain. An MRI/MRS scan will be run on the same day or near in time to the PET scan to detect structural changes and to assess gliosis (a proliferation of glial cells (the major type of brain cell)) through measurement of myoinositol (a chemical compound) which is elevated in gliosis. The MRI/MRS scan will serve as an additional descriptive measure of the increase in glial cells in the brain. 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. 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. All records are confidential and may not be disclosed without the subject's written permission and except that the FDA and/or funding agencies may inspect the records.
"PET Imaging Studies of Brain Dopamine: Changes in Subjects Infected with Human Immunodeficiency Virus (HIV)"
Principal Investigator: Dr. Gene-Jack Wang, Brookhaven National Laboratory
Project started in: 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: 12/18/01
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 6
Reporting period for number of human subjects:
Year prior to last IRB approval date
Type(s) of Human Subjects Involvement:
Clinical and laboratory studies indicate human immunodeficiency virus (HIV) infection frequently results in brain dopaminergic dysfunction and dementia. This dementia syndrome is called HIV – cognitive motor complex (CMC). The purpose of this study is to investigate changes in the brain dopamine system of subjects infected with HIV and the efficacy of highly active antiretroviral treatment. The study will compare 30 HIV subjects, 20-65 years of age who have not yet begun highly active antiretroviral medication, with 30 age matched healthy control subjects. Each evaluation will entail PET studies with 2 tracers to measure: postsynaptic DA sites ([11C]raclopride for dopamine D2 receptors) and presynaptic DA sites ([11C]cocaine for dopamine transporter). HIV subjects will be asked to repeat testing 6-12 months after treatment using the same 2 tracers. We predict that subjects with HIV dementia have a decrease in DA transporters, which leads to Parkinsonian signs and HIV-CMC. We postulate that these abnormalities are partially compensated with normal or up regulated DA receptors. We predict that effective highly active antiretroviral treatment will improve dopamine function. 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. Any area where the skin anesthetic will be applied may become red and/or irritated. 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. All records are confidential and may not be disclosed without the subject's written permission and except that the FDA and/or funding agencies may inspect the records.
"Effects of Estrogen Replacement on Brain Dopamine Function"
Principal Investigator: Dr. Nora D. Volkow, Brookhaven National Laboratory
Project started in: 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: 12/18/01
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 purpose of this study is to investigate the effects of estrogen replacement therapy in postmenopausal women on the age-related decline in brain dopamine activity and its consequences on cognitive and motor function. While there is evidence that estrogen replacement has a neuroprotective effect with respect to Alzheimer’s disease, little is known about its effects on the neurodegenerative changes that occur with age in the brain dopamine system. We will use Positron Emission Tomography (PET) to measure dopamine brain activity in postmenopausal women to assess the effects of estrogen replacement therapy in the age-related decline in brain DA activity. In parallel we will also evaluate neuropsychological performance to assess the relationship between the changes in brain dopamine activity and cognitive and motor performance. We will use [11C]cocaine to measure DAT and we will use [11C]raclopride with and without methylphenidate (brand name Ritalin) pretreatment to measure changes in extracellular dopamine. We will also perform an MRI to correct the PET measures for the age-related structural changes in the brain (cortical atrophy, ventricular enlargement). This protocol will use normal female subjects in the age range 55-75. We will study 10 normal female subjects per year over a three year period though if scheduling and recruitment rate permits we may complete this study in less than 3 years.
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. Any area where the skin anesthetic will be applied may become red and/or irritated. 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. 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. The MRI machine creates a strong magnetic field. Subjects with certain metal objects in their body, for example, metal fragments , non-removable hearing aids, nerve stimulators, or pacemakers, will not be allowed to enter the magnet area and cannot participate in this study. Subjects may be bothered by feelings of claustrophobia (“feeling enclosed”) while in the scanner. Because the MRI/MRS makes loud “knocking” noises, they will be asked to wear earplugs. While the MRI/MRS makes the “knocking” noise, they might feel a tingling sensation in your arms or legs, but it is unlikely that this will occur. They may become dizzy or experience a metallic taste in your mouth if they move their head quickly in the magnet. The radio waves produced by the scanner could cause a warm sensation, but this is unlikely. Although the long-term risk of exposure to the MRI/MRS machine is not known, there is no known long-term risk based on the information collected over the past 20 years. 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 and except that the FDA and/or funding agencies may inspect the records.
"PET Studies of Cocaine Abuse: Effects of Expectation"
Principal Investigator: Dr. Nora D. Volkow, Brookhaven National Laboratory
Project started in: 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: 12/18/01
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:
The purpose of this study is to compare the activation of the brain in response to intravenous methylphenidate (brand name Ritalin), a drug that, like cocaine, also blocks dopamine’s removal. Brain activation will be compared to when cocaine abusers are expecting to receive the drug versus to when they are not, and to assess if expectation can activate a similar circuit to that activated by the drug. For this purpose, we will measure regional brain glucose metabolism using 18FDG as a radiotracer, which serves as an index of brain function in current cocaine abusers under 4 different conditions: 1) subjects are told they will receive placebo and are given placebo; 2) subjects are told they will receive methylphenidate and are given placebo; 3) subjects are told they will receive methylphenidate and are given methylphenidate; and 4) subjects are told they will receive placebo and are given methylphenidate. We will study 20 active cocaine abusers over a three-year period. Each subject gets four 18FDG injections and each injection is given on a different day. An MRI scan is also run to assess structural abnormalities, such as atrophy.
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. 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. 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. All records are confidential and may not be disclosed without the subject's written permission and except that the FDA and/or funding agencies may inspect the records.
"PET Studies in Attention Deficit Disorder: Role of Dopamine"
Principal Investigator: Dr. Nora D. Volkow, Brookhaven National Laboratory
Project started in: 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: 01/24/02
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:
The purpose of this research is to assess if there are changes in the brain of subjects with ADHD. More specifically, we want to assess if there are abnormalities in brain dopamine, which is a chemical that regulates attention and motor activity in the brain. Dopamine is also the chemical that is affected by drugs used in the treatment of ADHD such as Ritalin