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: 73
"DNA Repair - Human and E. Coli Photoreactivating Enzymes"
Principal Investigator: Dr. Betsy M. Sutherland, Brookhaven National Laboratory
Project started in: 1977
This project ended in fiscal year 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: 03/02/99
Explanation of IRB approval:
Protocol was inactivated during its annual review 2/00.
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:
We are studying DNA damage and repair in human tissues. Our recent studies indicate that repair in human tissues is much more rapid than in human cells in culture, and make these studies critical to understanding the ability of people to cope with DNA damaging agents in the environment. We use white blood cells from healthy human volunteers in these experiments; the volunteers donate small quantities by approved medical procedure. After withdrawal of blood from the volunteers, the blood cells are separated and used as a source of photoreactivating enzyme, which repairs cyclobutyl pyrimidine dimers in DNA, as well as a source of non-cultured human cells for studies of DNA damage and repair. DNA damages are inflicted by ultraviolet lamps, a Cesium source or by HZE (high atomic number, high energy) particles. 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.
"New and Old Models in Body Composition: Ethnic Specificity"
Principal Investigator: Dr. Lucian Wielopolski, Brookhaven National Laboratory
Project started in: 1989
This project ended in fiscal year 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: 05/04/99
Explanation of IRB approval:
Protocol was inactivated 03/00.
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: 05/04/99 to 03/01/00
Explanation:
Protocol was inactivated 03/00.
Type(s) of Human Subjects Involvement:
Obesity and its associated medical complications represent a major health problem in black women. Evaluating the prevalence and underlying pathogenesis of obesity in black women requires accurate estimates of body fat and the metabolically active tissue mass. The aims of this project are to: 1) expand our subject pool to provide definitive coefficients for two-compartment models in women as a function of age, ethnicity and body fat; 2) model resting metabolic rate in relation to extensive body composition measurements in this diverse group of subjects; and 3) critically evaluate body composition methodology and models in tracking compartmental changes in obese women losing weight on a hypocaloric diet over three months. Elemental body compositions will be determined by whole body counting, in vivo neutron activation analysis and tritiated water dilution method. Human subjects will be exposed to ionizing radiation including neutrons, gamma-rays and electrons. Subjects will be given tritiated water by mouth. 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. 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.
"Nutritional and Intestinal Consequences of Immunodeficiency States"
Principal Investigator: Dr. Lucian Wielopolski, Brookhaven National Laboratory
Project started in: 1989
This project ended in fiscal year 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: 05/04/99
Explanation of IRB approval:
Protocol was inactivated 03/00.
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: 05/04/99 to 03/01/00
Explanation:
Protocol was inactivated 03/00.
Type(s) of Human Subjects Involvement:
Previous studies documented the frequent occurrence of severe, progressive malnutrition in Acquired Immune Deficiency Syndrome (AIDS). The long-term goals of this study are to provide an understanding of the pathogenesis of malnutrition in AIDS, a scientific rationale for nutritional therapy, and realistic expectations for the results of such therapy. The specific aims of this proposal are to define the metabolic mechanisms underlying the alterations in body composition that occur as a result of AIDS, their association with active Human Immunodeficiency Virus(HIV)infection, and their relationship to altered release of cytokines. The centerpiece of these studies will be precise measurements of body composition which will allow precise determination of depletion or repletion. Elemental body compositions will be determined by whole body counting and in vivo neutron activation analysis. Subjects will be exposed three times per year to ionizing radiation including neutrons, gamma-rays and electrons. 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 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 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.
"Health Surveillance System"
Principal Investigator: Dr. Bryce D. Breitenstein, Brookhaven National Laboratory
Project started in: 1991
This project ended in fiscal year 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: 02/01/00
Explanation of IRB approval:
Protocol was inactivated by PI 08/00.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 3200
Reporting period for number of human subjects:
Year prior to last IRB approval date
Type(s) of Human Subjects Involvement:
The Department of Energy (DOE) has developed a Health Surveillance System (HSS) to monitor significant causes of morbidity and death among active DOE contractor employees. The HSS focuses on enhancing the DOE's ability to monitor the health of its workers and provide an early warning of threats to worker's health. The Brookhaven National Laboratory (BNL) Occupational Medicine Clinic (OMC) participates in this project by providing information regarding all BNL employees, who work half time or greater, to the DOE. This information is collected as part of the routine operations of the Clinic. The identifying information linking this information to an individual is encoded by the OMC prior to transmission. The key for decoding the identifier is maintained exclusively by the BNL-OMC. The employee population is approximately 3,200. 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.
"Photoreactivation in Human Skin"
Principal Investigator: Dr. Betsy Sutherland, Brookhaven National Laboratory
Project started in: 1991
This project ended in fiscal year 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: 03/02/99
Explanation of IRB approval:
Protocol was inactivated at its annual review 02/00.
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:
We are investigating induction of DNA damage by ultraviolet light in the absence and presence of substances applied topically to skin that may alter the transmission of skin and thus affect the level of DNA damage. In collaboration with K. Kaidbey, M.D., Ivy Laboratories, we are evaluating the effects of alpha hydroxy acid (active ingredient in anti-wrinkle creams) or of Imiquimod (causes regression of warts in non-sunlight exposed areas and is now a candidate for treatment of actinic keratoses on sunlight-exposed skin) on induction of cyclobutyl pyrimidine dimers. After UV exposure (and including unirradiated or sham-irradiated controls), 3 to 6 mm-diameter epidermal biopsies are obtained using lidocaine, a local anesthetic. The biopsies are sent to BNL for analysis. A small amount of bleeding at the biopsy site can occur and is stopped immediately by treatment with a routinely-used topical chemical. The volunteer is instructed to apply an ointment and bandaid to these spots daily after bathing for one week.
Risks include sunburn or allergic reactions from the suntan lamps or topical agents. Although uncommon, persons may get allergic reactions from treatment (red, itchy, bumpy rashes). Risks from having skin biopsies performed include bruising on the arm, scarring or dark coloration of the biopsy site. Very unusually, skin biopsy sites may become infected, or persons can have allergic reactions to the lidocaine or topical ointment.
Approximately 30 studies per year are performed, All solicitation of volunteers, experimental treatments, and obtaining of biopsies is carried out at Ivy Laboratories under approval of the Schulman Associates Institutional Review Board, Inc. and with informed consent of the volunteers at Ivy Labs. We also study human neonatal foreskins (10-15/year) obtained from Suffolk Central or Brookhaven Hospital. The tissue, which would otherwise be discarded, serves as an excellent source of human tissue for studies of DNA damage and for initiation of cell cultures for in vitro studies. Anonymity of mother and child is maintained to preserve confidentiality; because of the nature of the tissue, no subject is sampled more than once. 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 18-FDG in the Diagnosis of Glucose Metabolism in the Human Body (Tumors)"
Principal Investigator: Dr. Joanna S. Fowler, Brookhaven National Laboratory
Project started in: 1994
This project ended in fiscal year 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: 01/05/99
Explanation of IRB approval:
Protocol was inactivated at its annual review 12/99.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 3
Reporting period for number of human subjects:
Other: 01/01/99 to 12/01/99
Explanation:
Protocol was inactivated at its annual review
Type(s) of Human Subjects Involvement:
The purpose of this protocol is to evaluate functional changes of normal brain tissue in patients undergoing radiation therapy for brain tumors. Approximately 25 patients will be studied, including follow-up patients from prior years. Each patient will be studied up to four times per year: at baseline, after radiation, and two or four months later. The subjects have a short-lived positron emitter tracer (F-18-Fluorodeoxyglucose or F-18-FDG) administered and are subsequently scanned with positron emission tomography (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 (880 mrem) has been reported. The estimation of risk of harm can be obtained only by extrapolation from much higher doses. 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.
"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
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: 01/04/00
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 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.
"Studies of Brain Aging"
Principal Investigator: Dr. Joanna S. Fowler, Brookhaven National Laboratory
Project started in: 1994
This project ended in fiscal year 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: 08/04/99
Explanation of IRB approval:
Protocol was inactivated by the PI 04/00
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: 08/04/99 to 04/25/00
Explanation:
Protocol was inactivated by PI 04/00
Type(s) of Human Subjects Involvement:
Dopamine is a neurotransmitter which is involved in movement and in cognition. The nerve cells producing dopamine are especially vulnerable and are progressively lost in the normal aging human brain. It has been postulated that some of the motor impairment and cognitive changes that occur in the elderly are associated with the loss in dopaminergic neurons. The purpose of this study is to investigate age-related changes in brain dopamine activity and neuronal loss and its consequences on brain function.
The study will use normal subjects in the age range of 20-95 who will be studied with 4 tracers. In this study we will measure 4 parameters: dopamine nerve terminals, dopamine receptors, brain function and MAO B (neuron loss is accompanied by the proliferation of glial cells which are rich in monoamine oxidase B or MAO B). The tracers are d-threo-[11C]- methylphenidate, [11C]-Raclopride, [18F]-fluoro deoxyglucose and [11C]L-Deprenyl-D2. We will study 120 normal subjects, including approximately 10 males and 10 females per decade of age. Subjects will be recruited from newspaper ads and by word of mouth. Each subject will be studied with 4 tracers. In parallel, a complete neurological evaluation is performed in all subjects to determine the cognitive and motor consequences of age-related degeneration of the dopamine system. The studies will be carried out within 6 weeks. However, when possible, the four tracer studies will be completed in two days to minimize the number of catheterizations. The subjects have a short-lived positron emitter tracer administered and are subsequently scanned with positron emission tomography (PET).
A potential side effect of radiation is the induction of cancer. However, no harm in a human individual or a large population exposed at doses as low as those delivered in this procedure (1840 mrem) has been reported. The estimation of risk of harm can only be obtained 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 a 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.
"Vaccine Intervention for Lyme Borreliosis"
Principal Investigator: Dr. John J. Dunn, Brookhaven National Laboratory
Project started in: 1994
This project ended in fiscal year 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: 09/14/99
Explanation of IRB approval:
Protocol was inactivated at its annual review 8/00
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:
Abstract:
The major objective of this proposal is to achieve safe, effective, rationally designed second generation recombinant vaccines to prevent Lyme borreliosis. All experiments involving human subjects will be conducted at State University of New York at Stony Brook: Serological assays involving human serum will be performed on coded specimens with the investigators blinded to clinical information pertaining to individual samples. No subject identifying information will be available to the investigator. Test samples acquired as part of clinical studies include subjects of all ages, sexes and races.
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.
Studies performed at Brookhaven National Laboratory are conducted on cultured Lyme Disease spirochetes (bacteria) and involve DNA sequencing and construction and expression of recombinant DNAs for use as reagents in diagnostics and vaccine intervention.
"Boron Neutron Capture Therapy (BNCT) of Glioblastoma Multiforme at the BMRR (Prior Radiation)"
Principal Investigator: Dr. Jeffrey A. Coderre, Brookhaven National Laboratory
Project started in: 1995
This project ended in fiscal year 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: 01/04/00
Explanation of IRB approval:
Protocol was inactivated by PI 06/00.
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 objective of this study is to evaluate the safety of a marginally higher and conceivably more hazardous dose of radiation in the normal brain than is tested under the companion protocol (BNL-95-260). A total of five patients with glioblastoma multiforme will be studied using BNCT following a two hour intravenous infusion of p-boronophenylalanine-fructose (10-BPA-F) at a dose of up to 370 milligrams (mg) 10-BPA per kilogram (kg). The peak dose to normal brain shall be ~12.6 gray equivalent (Gy-Eq) delivered at a dose rate of approximately 27 centigray equivalent per minute (cGy-Eq/min). The deepest contrast enhanced tumor margin shall be between 6 centimeters (cm) and 6.8 cm from the scalp surface and the patient will have received no more than 500 cGy of brain irradiation. The biodistribution phase may be dispensed with for those patients who have had more than one craniotomy or whose contrast enhanced computed tomography (CT) and/or magnetic resonance imaging (MRI) scans show no residual tumor at the time of referral for BNCT. Repeat BNCT shall not be performed under this protocol. During the BNCT procedure at the epithermal neutron beam of the Brookhaven Medical Research Reactor (BMRR), the patients are exposed to high LET radiations (alpha-particles and Li-7 nuclei) resulting from the capture of slow "thermal" neutrons by 10-B nuclei and to protons and gamma photons. The patients receive up to 370 mg/kg of 10-BPA-F intravenously in conjunction with debulking craniotomy and/or in conjunction with the BNCT procedure. For the biodistribution phase of the study, 10-BPA-F is infused intravenously for 1-2 hours prior to the surgical debulking of the tumor. Samples of the tumor, including normal brain tissue, if any, and blood are analyzed for 10-B content. For the BNCT phase of the study, 10-BPA-F is injected intravenously over 1-2 hours. Approximately 1 hour following the completion of the infusion, the patient's head is exposed to the epithermal neutron beam. Complications may include nausea, vomiting, brain swelling, headaches, muscular weakness, loss of coordination, somnolence, seizures, stupor, memory loss, hearing loss, impaired speech, alopecia, ulceration and necrosis of scalp, cataracts, blindness, skull bone necrosis, loss of bodily functions due to brain damage, coma, or death. Recruitment of new subjects to this protocol was terminated in March, 1996. 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.
"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: 07/11/00
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 31
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.
"BNCT of GBM at the BMRR: A Phase I/II Dose Escalation Study"
Principal Investigator: Dr. Jeffrey A. Coderre, Brookhaven National Laboratory
Project started in: 1996
This project ended in fiscal year 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: 01/04/00
Explanation of IRB approval:
Protocol was inactivated by the PI 06/00.
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 safety of p-boronophenylalanine-fructose (BPA-F) in a dose escalation study, the safety of increasing average brain boron neutron capture therapy (BNCT) dose, the safety of increasing the minimum target volume BNCT dose and the safety of single field versus double field BNCT. Patients with glioblastoma multiforme will be irradiated using the epithermal neutron beam at the Brookhaven Medical Research Reactor (BMRR), following an infusion of BPA-F. During the BNCT procedure at the BMRR, the patients will be exposed to high LET radiations (alpha- particles, Li-7 nuclei) resulting from the capture of slow "thermal" neutrons by 10-B nuclei and to protons and gamma photons. The subjects will receive up to 495 milligrams BPA per kilogram body weight as BPA-F injected intravenously for 2-3 hours. Approximately 1 hour after the completion of the infusion, the patient's head is exposed to the epithermal neutron beam. Complications may include nausea, vomiting, brain swelling, headaches, muscular weakness, loss of coordination, somnolence, seizures, stupor, memory loss, hearing loss, impaired speech, alopecia, ulceration and necrosis of scalp, cataracts, blindness, skull bone necrosis, loss of bodily functions due to brain damage, coma or death. Approximately 28 subjects will be studied. 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 Obesity"
Principal Investigator: Dr. Joanna S. Fowler, Brookhaven National Laboratory
Project started in: 1996
This project ended in fiscal year 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: 07/13/99
Explanation of IRB approval:
Protocol was inactivated by the PI 04/00.
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: 07/13/99 to 04/01/00
Explanation:
Protocol was inactivated 04/00.
Type(s) of Human Subjects Involvement:
The purpose of this study is to investigate if there are changes in the brain dopamine system of obese individuals and to assess if these reverse to normal with weight loss. The study will use twenty normal obese subjects in the age range of 30-55 years of age. Each evaluation will entail studies with three tracers: to measure the dopamine nerve terminals - d-threo-11C-methylphenidate; to measure postsynaptic dopamine sites - 11C-raclopride; and to measure regional brain function - 18F-fluorodeoxyglucose. 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 (3440 mrem) has been observed. Thus, estimation of the 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 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 consent, except 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.
"Weight Loss: Bone and Muscle Skeletal Homeostasis"
Principal Investigator: Dr. Lucian Wielopolski, Brookhaven National Laboratory
Project started in: 1996
This project ended in fiscal year 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: 08/04/99
Explanation of IRB approval:
Protocol was inactivated 03/00
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 15
Reporting period for number of human subjects:
Year prior to last IRB approval date
Type(s) of Human Subjects Involvement:
This study will investigate the loss of both skeletal muscle and bone during a hypocaloric diet of 900 kcalories per day, which will be taken by a group of obese women with a body mass index (BMI) above 28. The hypotheses are that both skeletal muscle and bone mass are lost during weight loss on the prescribed diet and that loss of components of fat-free mass (FFM) will be greater in post-menopausal than in pre-menopausal women. The loss of skeletal mass during weight loss will be evaluated by two techniques: dual energy x-ray absorptiometry (DEXA) and in vivo neutron activation (IVNA). 144 obese subjects will be studied over a 4 year period. Subjects will have three sets of assays: before and after a period of weight loss, and a third time after 24 weeks of weight loss. 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 (709 mrem) has been reported. The estimation of risk of harm can be obtained only by extrapolation from much higher doses. 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 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
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: 12/14/99
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 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.
"Quantitative Studies on the Oncogenic and Cytogenetic Effects of Energetic Iron Particles in Mammalian Cells"
Principal Investigator: Dr. Dennis Morrison, NASA Johnson Space Center
Project started in: 1997
This project ended in fiscal year 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: 10/05/99
Explanation of IRB approval:
Protocol was inactivated by the PI 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:
The study is to investigate the cytogenetic effects of energetic heavy ions, including 1 GeV/u iron particles, in human cells. The primary goal of the proposed experiments is to determine the relative biological effectiveness (RBE) and the repair kinetics of chromosomal damages induced by high-energy ions, especially 1 GeV/u iron particles. Whole blood will be obtained from healthy volunteers and irradiated at six different doses ranging from 20 to 300 cGy. Three subjects will have 50-100 ml of blood drawn per year. There will be no repeat studies. Whenever blood is removed, there is minor discomfort and a slight possibility of local bleeding into the tissues. Records are confidential and may not be disclosed except by the subject's written consent with the exception that the FDA and/or other funding agencies may inspect the records. Documented informed consent is obtained from all subjects in a manner compliant with all federal regulations.
"Boron Neutron Capture Therapy of Glioblastoma Multiforme at the Brookhaven Medical Research Reactor: A Phase I/II Dose Escalation Study (FDA IND 43,317, Protocol #5)"
Principal Investigator: Dr. Jeffrey A. Coderre, Brookhaven National Laboratory
Project started in: 1998
This project ended in fiscal year 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: 01/04/00
Explanation of IRB approval:
the protocol was inactivated by the PI 06/00.
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:
Single Fraction Boron Neutron Capture Therapy (BNCT) irradiation will be administered to patients 18 years of age or older, with a specific type of tumor (supratentorial, unilateral, unifocal glioblastoma mulitforme [GBM]). The BNCT procedure will be carried out no sooner than 3 weeks following the surgical excision of the GBM. The BNCT irradiation will be administered approximately one hour following an intravenous infusion of boronophenylalanine-fructose solution. The minimum tumor volume radiation dose will be~30 Gy-Eq. The minimum target volume (tumor volume and volume of edema surrounding the tumor plus the volume of a 2 cm- thick shell that encloses the zone of edema as seen on the pre-operative brain scans) radiation dose will be ~ 29 Gy-Eq. Up to 14 patients will be enrolled. Other eligibility criteria will also be considered. There will be no repeat studies under this CIRC. Those patients who are found ineligible for CIRC 266A (Protocol #5) will be evaluated for eligibility for CIRC #286.
Complications may include nausea, vomiting, brain swelling, headaches, muscular weakness, loss of coordination, somnolence, seizures, stupor, memory loss, hearing loss, impaired speech, alopecia, ulceration and necrosis of scalp, cataracts, blindness, skull bone necrosis, loss of bodily functions due to brain damage, coma or death. 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
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: 11/02/99
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 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 Evaluation of Human Epilepsy"
Principal Investigator: Dr. Hoby Hetherington, Brookhaven National Laboratory
Project started in: 1998
This project ended in fiscal year 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: 11/02/99
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:
The goal of this study is to evaluate the sensitivity and specificity of NMR Spectroscopic Imaging (NMRSI) in localizing and lateralizing epileptogenic tissue in patients with intractable epilepsy. Data will be collected using a 4T whole-body NMR system. Patients will be fitted with an NMR detector and images will be acquired for up to two hours. To enhance the accuracy of the clinical lateralization of the epileptogenic region, high resolution quantitative FDG-PET studies, a clinically accepted diagnostic test, will also be acquired. No other interventions will be used. Twenty epileptic subjects and twenty control subjects will be studied and there will be no repeat studies. The study is considered to involve minimal risk. No serious ill effects have been reported to date from any site operating with this 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. If they have any of the above, or other foreign metallic objects in their body, they will not be allowed to participate in the study. 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. If they choose, they will be able to exit the magnet at any time during the examination. 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. The magnet is thought to exert a force on the fluid within the semi-circular canals near the ears, giving a sensation of dis-equilibrium. The sensations go away if the head is kept still or other motion ceases. Subjects will be given ear plugs to block some of the noise of the machine. Possible risks due to FDG-PET studies are listed below. 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 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.
"PET Studies of the Effects of Tobacco Smoke on the Human Brain"
Principal Investigator: Dr. Joanna S. Fowler, Brookhaven National Laboratory
Project started in: 1998
This project ended in fiscal year 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: 11/02/99
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:
Part 1: Is MAO inhibition greater immediately after smoking and how long does MAO inhibition last after cigarette withdrawal?
Studies to be performed in two groups of smokers (total of 12 smokers, 20-75 years old). Each subject will have at least two PET scans on the same day and, in subjects willing to quit smoking, there will be follow-up PET scan at one week and one month to determine how rapidly MAO levels will recover to normal values.
Part 2: Can MAO inhibition be observed after smoking a single cigarette?
Non-smokers who have had prior experience smoking a cigarette (so that they know they can tolerate cigarette smoke), but who have never smoked regularly, will be asked to smoke a single cigarette to determine whether MAO inhibition occurs acutely or whether it is a long term effect (total of 8 non-smokers, 20-75 years old). There will be two PET scans on the same day, one before and one after the cigarette. Former smokers will not be included because of the risk of resuming smoking.
Part 3: Do smokers have different levels of dopamine transporters and dopamine receptors than non-smokers?
Each subject will have two scans, one with[11C]d-threo- methylphenidate and one with [11C] raclopride, preferably on the same day (total of 20 smokers, who have smoked for at least 25 years, and 20 never smokers, age range 55-70 years old). 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. 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.
"Spectroscopic Studies in Drug Abusers"
Principal Investigator: Dr. Nora D. Volkow, 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: 12/14/99
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 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.
"Cerebral Metabolism in Ketosis and Epilepsy: A Spectroscopic Study at 4T"
Principal Investigator: Dr. Jullie Pan, Brookhaven National Laboratory
Project started in: 1998
This project ended in fiscal year 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: 01/05/99
Explanation of IRB approval:
Protocol was inactivated at its annual review 12/99.
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 is a study using magnetic resonance (MR) spectroscopy to assess how the ketogenic (high fat) diet alters cerebral metabolism in relation to its control of seizures. Patients with intractable epilepsy who are being treated by their physician with the ketogenic diet will be studied using MR spectroscopy before and one month after initiation of the diet. The MR studies will be performed with two separate acquisitions, one performed before diet initiation and another one month after diet initiation. The maximum number of patients studied will be 36. 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 Multiple Sclerosis by 1H MR Spectroscopy"
Principal Investigator: Dr. Jullie Pan, Brookhaven National Laboratory
Project started in: 1998
This project ended in fiscal year 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: 12/14/99
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 30
Reporting period for number of human subjects:
Other: 08/01/98 to 12/01/99
Explanation:
Total of 14 new subjects during 1999 2 subjects (not included in the above) were claustrophobic Total of 16 new subjects during 1998 No new subjects during 2000
Type(s) of Human Subjects Involvement:
This is a serial study of patients with multiple sclerosis and its disease subtypes. The goals are to 1) define the clinical subtypes using MR spectroscopy, and 2) to determine how the disease evolves with therapy using MR spectroscopy. The number of patients to be studied is 28, although up to 35 may be recruited. These patients will be studied serially every four months; over twelve months they will be studied three times each. The patients studied for Goal 1 will also serve as the initial time port for Goal 2. With a drop out rate that may vary from 10 to 35%, the actual number of patients recruited will probably range from 30 to 35. 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.
"Cerebral Metabolism in Functional Stimulation: A Combined 1H-13C Magnetic Resonance and PET Study"
Principal Investigator: Dr. Jing-Huei Lee, Brookhaven National Laboratory
Project started in: 1998
This project ended in fiscal year 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: 02/01/00
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:
Functional cerebral activity, such as sensory input or motor activity causes increased cerebral blood flow. Whether this increase is accompanied by an increased cerebral metabolic rate is unclear. Conflicting data have not resolved these questions, partly due to methodologic differences. The relevancy of this question is clear, since it relates to the basic needs of the brain with mental activity and thus potentially impacts on issues such as brain ischemia and encephalopathy. In this study we will be using both PET and MR to measure changes in cerebral metabolic rate with visual stimulation in humans (subjects will view a flashing checkerboard pattern). Each subject will undergo four MR studies and two PET studies performed over a total of one and half months. Two of the MR studies are optimization studies; the remaining two MR and two PET studies will be performed within four weeks. All the studies will involve infusions that control the volunteer's blood glucose levels; the PET studies will also use 2-18FDG as the radiotracer. The number of subjects studied will be twenty-four normal subjects, male and female.
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 (1540 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 Evaluation of the Effect of Ginko Biloba on Brain Monoamine Oxidase (MAO)"
Principal Investigator: Dr. Joanna S. Fowler, Brookhaven National Laboratory
Project started in: 1998
This project ended in fiscal year 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: 04/06/99
Explanation of IRB approval:
Study was inactivated at its annual review 3/00.
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 extract of ginko biloba (referred to as EGb 761) is one of the most popular alternative medicines used to improve memory and cognition. It has been approved in Europe for the treatment of dementia and a recent clinical trial of outpatients with who were mildly to severely demented with Alzheimer's disease showed that ginko is safe and that it improves cognitive and social functions. In spite of ginko's widespread use, there have been no studies to determine how it affects the human brain. This is an important question given the widespread use of the extract and its apparent beneficial effects. Monoamine oxidase (MAO) is an enzyme which breaks down neurotransmitters (substances which are necessary for communication between nerve cells). Drugs which inhibit MAO (MAO inhibitors) are effective in the treatment of Parkinson's disease and depression. It has recently been discovered that ginko inhibits MAO in animals suggesting that it may be acting similar to MAO inhibitor drugs. However, this has not been shown in humans. In this study a positron emission tomograph (PET), a medical imaging device, and the radiotracers [11C]clorgyline and [11C]L-deprenyl-D2 will be used to determine whether treatment with ginko biloba inhibits MAO A and MAO B in the brain. Normal subjects (20-75 years old) will be scanned with both radiotracers before taking ginko and then rescanned with both radiotracers 4-6 weeks later after taking ginko (120 mg/day) for 4 weeks. We will recruit 10 normal, non-smoking subjects. We expect that a sample size of 5 will allow us to answer this question but a sample size of 10 is requested in the event that the magnitude of the effect is small and a larger sample size is required to achieve significance. This will be important information for understanding how ginko works and may also suggest other treatments to improve brain function. 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 (420 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.
"Regional Ethanol Uptake Kinetics and MRI Visibility of Human Brain by 1H MRI Imaging"
Principal Investigator: Dr. Jullie Pan, Brookhaven National Laboratory
Project started in: 1998
This project ended in fiscal year 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: 04/06/99
Explanation of IRB approval:
Protocol was inactivated at its annual review 3/00.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 1
Reporting period for number of human subjects:
Year prior to last IRB approval date
Type(s) of Human Subjects Involvement:
Recently, the NMR visibility of ethanol has been correlated with the acute and chronic tolerance of its intoxicating effects and shown to vary strongly between different brain structures. The degree of visibility is related to the degree of interaction of ethanol with biological membranes, with increased visibility associated with a lower degree of interaction. Further, the intoxicating effects of ethanol have been linked with the degree of interaction with biological membranes. The goal of this study is to evaluate the regional kinetics of uptake and NMR visibility of ethanol in the human brain to better understand its biologic effects. To evaluate the mechanisms of interaction and general membrane association versus specific binding sites, we will carry out ten studies at three different dose levels each (a total of 30 studies). Repeat studies (same volunteer at different dose levels) are not required, however, they will not be excluded. The thirty studies will be carried out over the next year.
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.
"Two Fraction Boron Neutron Capture Therapy of Debulked Glioblastoma Multiforme at the Brookhaven Medical Research Reactor: A Phase I/II Dose Escalation Study (FDA IND 43,317, Protocol #6)"
Principal Investigator: Dr. Jeffrey A. Coderre, Brookhaven National Laboratory
Project started in: 1998
This project ended in fiscal year 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: 06/01/99
Explanation of IRB approval:
Protocol was inactivated at its annual review 5/00.
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:
Patients with suprratentorial, unilateral, unifocal glioblastoma mulitforme (GBM), who fail to qualify for CIRC #266A because the minimum tumor volume and target volume radiation doses could not be delivered without exceeding the normal tissue radiation tolerance limits, will be evaluated for eligibility for CIRC #286 (Protocol #6). Two fraction Boron Neutron Capture Therapy (BNCT) irradiation, with a minimum interval of ~ 48 hours between the two fractions, will be administered to patients 18 years of age or older. The BNCT procedure will be carried out no sooner than 3 weeks following the surgical excision of the GBM. Each irradiation will be carried out approximately one hour following an intravenous infusion of boronphenylalanine- fructose. The minimum tumor volume dose will be 30 Gy-Eq. The minimum target volume (pre-operative tumor and peritumoral edema volume plus a 2 cm-thick shell that encloses it) dose will be ~ 17 Gy-Eq. Other eligibility criteria will also be considered. Fourteen patients will be enrolled. There will be no repeat studies under the CIRC.
Complications may include nausea, vomiting, brain swelling, headaches, muscular weakness, loss of coordination, somnolence, seizures, stupor, memory loss, hearing loss, impaired speech, alopecia, ulceration and necrosis of scalp, cataracts, blindness, skull bone necrosis, loss of bodily functions due to brain damage, coma or death. 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.
"Two Fraction Boron Neutron Capture Therapy of Non-Debulked Glioblastoma Multiforme at the Brookhaven Medical Research Reactor: A Phase I/II Dose Escalation Study (FDA IND 43,317, Protocol #7)"
Principal Investigator: Dr. Jeffrey A. Coderre, Brookhaven National Laboratory
Project started in: 1998
This project ended in fiscal year 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: 06/01/99
Explanation of IRB approval:
Protocol was inactivated at its annual review 5/00.
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:
Patients with supratentorial, unilateral, unifocal glioblastoma multiforme (GBM), in whom the surgical excision of the GBM could not be carried out because of the location the tumor or age of the patient, will be considered for eligibility to CIRC #287 (Protocol #7). The maximum pre-operative tumor volume shall not exceed 50 cc. Two fractions of Boron Neutron Capture Therapy (BNCT) irradiation will be administered to subjects 18 years of age or older and each fraction of radiation will be separated by a minimum interval of ~ 48 hours. The BNCT procedure will be carried out no sooner than 2 weeks following the biopsy or minimally invasive surgical excision of the GBM. Each BNCT irradiation will be administered approximately one hour following an intravenous infusion of boronphenylalanine-fructose solution (BPA-f). The minimum tumor volume dose shall be ~ 30 Gy-Eq. The minimum target volume dose shall be ~ 17 Gy-Eq.
Fourteen patients will be enrolled. Other eligibility criteria will also be considered. Complications may include nausea, vomiting, brain swelling, headaches, muscular weakness, loss of coordination, somnolence, seizures, stupor, memory loss, hearing loss, impaired speech, alopecia, ulceration and necrosis of scalp, cataracts, blindness, skull bone necrosis, loss of bodily functions due to brain damage, coma or death. 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.
"Boron Neutron Capture Therapy of Recurrent Glioblastoma Multiforme at the Brookhaven Medical Research Reactor: A Phase I/II Dose Escalation Study (FDA IND 43,317, Protocol #8)"
Principal Investigator: Dr. Jeffrey A. Coderre, Brookhaven National Laboratory
Project started in: 1998
This project ended in fiscal year 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: 06/01/99
Explanation of IRB approval:
Protocol was inactivated at its annual review 5/00.
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 Subje