Ms. Ann M. Shirley
PO Box 2008
MS 6260
MS 6103
Oak Ridge, TN Anderson 37831-6103
Phone: 423-576-8022
Fax: 423-574-4084
Email: shirleyam@ornl.gov
Projects are approved by an IRB located at: Oak Ridge National Laboratory.
The approving IRB operates under a Multiple Project Assurance (MPA) recognized by DOE or by the Department of Health and Human Services (HHS).
MPA number of the IRB: M-1394
Number of Human Subjects Projects reported: 10
Project Identifier: ORNL-93-17
Project Title:
Measurement of Environmental Tobacco Smoke Constituents in Occupied Spaces
Principal Investigator:
Dr. Roger A. Jenkins
Project started in: 1993
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project used human subjects in Fiscal Year 1998.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Expedited
Most Recent Approval: August 03, 1998
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 278
Type of Human Subjects Involvement:
Objectives
The purpose of this study has been to determine the personal exposure to environmental tobacco smoke (ETS) of non-smoking subjects in occupational and away-from-work settings. Exposures have been related to occupational categories, living and working environments, and demographic factors.
Methodology
Individual participants wore one of two personal sampling pumps, one each at work and away-from-work. (For Phase 2, restaurant and tavern servers wore only one sampling system: in their workplace.) Samples of breathing zone air were collected, and analyzed for both particle- and vapor-phase markers of environmental tobacco smoke (ETS), including respirable suspended particulate matter, UV-absorbing and fluorescing particulate matter, scopoletin, solanesol, nicotine, 3-ethenyl pyridine, and myosmine. In addition, prior- and post-exposure saliva samples were collected by having the subjects chew on a piece of cotton dental dam in order that the smoking status can be assessed through cotinine levels. In the first phase of this study, 1566 subjects participated in the study. The subjects were distributed geographically around the United States, with about 100 subjects in each of 16 urban areas. In the second phase of the study, 165 subjects participated. All were recruited form the Knoxville, TN Standard Metropolitan Statistical Area.
In the course of analyzing the data from the first phase of the study, it was determined that for one of the targeted occupational groups, waiters/waitresses/bartenders, there was an insufficient number of subjects in the study pool to confidently distinguish exposure differences. For that reason, we are increasing the subject pool by about 165 subjects. This will increase the overall study population by about 11%, to approximately 1729 subjects. All of the added subjects will be recruited from the aforementioned occupational category in one of the urban areas studied in the first phase: Knoxville, TN. Essentially, the same experimental protocol as that previously employed will be used to judge occupational exposure. Area samplers were also placed in the subjects' place of employment. Phase 3, planned to begin near the beginning of FY98, will involve about 240 subjects and have a sampling and subject protocol identical to that of Phase 1. However, subjects will be recruited to fill specific demographic categories so that the overall study population will be representative of the non-smoking population from which the subjects were recruited.
Exposure of Human Subjects
Human subjects are not exposed to any experimental atmospheres, or anything else that they would not encounter in their daily occupational or non-occupational routines. The purpose of the investigation is to determine the extent of natural exposure to ETS.
Involvement of Human Subjects
Procedures
Two aspects of the study qualify it for human studies consideration. First, a sample of saliva will be acquired from each subject upon the entrance into and departure from the study. Depending on timing, sample acquisition could be as little as 24 hours or as much as 72 hours apart. The purpose of the saliva collection is to determine the concentration of a nicotine metabolite (cotinine) present. Salivary cotinine levels are used to confirm the absence of smoking among self reported non-smokers, and to determine the potential efficacy of use of salivary cotinine as a quantitative indicator of ETS-nicotine exposure. Saliva samples will be used for no other purposes.
Secondly, a great deal of demographic and exposure information is gathered on the subjects, which could not be collected via normal observation of the subjects. The confidentiality of the subjects is protected by several measures. First, subjects are assigned an identification number when they enter the study. The only place where the subject's name and address is tied to the identification number is on the written questionnaires which they complete. These questionnaires are stored in files maintained at ORNL in a restricted access area. A contractual requirement of any firm sub-contracted to recruit subjects or assist with field operations is that they make no permanent copies of the written questionnaires. In no place on the electronic data bases developed for the study are the subjects identified by anything other than a participant identification number.
Risks
Risks to the subjects are minimal. Subjects are asked to partake in normal activities, and are cautioned against wearing the sampling pumps around heavy machinery or during other activities in which wearing the sampling pump may compromise their safety. Subject names and addresses are only stored in hard copy (no electronic copy) in a restricted access area (combination lock access). Subject confidentiality is protected through the use of pseudo-identifiers. Acquisition of saliva samples is minimally invasive, and amounts to having to chew on a sterile piece of cotton dental dam for 60 seconds, and expelling it into a sterile vial. A videotape training film of 15-20 minutes in length is produced for each experimental protocol, and augments the formal human studies consent form.
Project Identifier: ORNL-94-33
Project Title:
Characterization of Components of Fingerprints
Principal Investigator:
Dr. Michelle V. Buchanan
Project started in: 1994
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project used human subjects in Fiscal Year 1998.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: August 03, 1998
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 30
Type of Human Subjects Involvement:
This project will chemically characterize the components present on the fingertip skin to determine if information about age, sex, and personal habits can be ascertained. In the next year, we will be building a data base from information obtained from a number of people to determine general trends and identify specific compounds that might be useful for distinguishing individuals based on skin components. The long term goal of the project is to obtain methodologies that can be used in forensic applications, but could also lead to non-invasive clinical assays. Samples will be obtained by asking the subject to wipe a fingertip across a clean glass surface in order to collect the material from the skin. After the sample is returned to the lab, then the materials will be removed from the surface by solvent wash. This protocol will NOT expose the subject to any chemicals (or other hazards). No risks to the subject are involved. During FY 98, we are finalizing sample processing protocols (work up of samples in the lab) and will only test 20 to 30 subjects (some of them numerous times).
Project Identifier: ORNL-94-38
Project Title:
Advanced Robotics for Remanufacturing and Aircraft Support Functions
Principal Investigator:
Dr. John V. Draper
Project started in: 1994
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project used human subjects in Fiscal Year 1998.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: August 01, 1998
Number of Human Subjects who participated in this project/protocol during
08/01/97 - 08/01/98: 4
Type of Human Subjects Involvement:
Objectives: This report describes preliminary testing to garner feedback about the heavylift dexterous manipulator (HDM) arm from experienced fighter load crewmen. The purpose of the testing was to provide preliminary information about control system parameters and to gather feedback from users about manipulator arm functionality. To that end, subjects interacted with the next generation munitions handler (NGMH) in informal testing sessions and provided feedback about the performance of the system. Certain control system parameters were changed during the course of the testing and feedback from the participants was used to make a rough estimate of "good" initial operating parameters. Later, formal testing will concentrate within this range to identify optimal operating parameters.
Ionizing radiation, radioactive substances, chemical substances: Human subjects were not exposed to any ionizing radiation, radioactive substances, or chemical substances during testing.
Methodology: Operational safety was an important concern during this testing program because of the nature of the HDM and its payloads, and because of the relative inexperience of the load crews with the NGMH program. For that reason, the first half-day of the testing program was devoted to a formal briefing on the NGMH project and testing program safety. Subject safety was further safeguarded by: (1) presence of a safety observer, who held a switch enabling him to shut down the manipulator arm in the event of an unplanned incident; (2) presence of a test observer, who monitored control system parameters and manipulator function via computer, and who could shut down the system should a problem appear; and (3) the deadman switch built into the manipulator controller, which shuts down the manipulator if the handle is released.
The testing itself was conducted using an informal format that encouraged the participants to interact with the HDM in a manner that allowed them to become familiar with its capabilities. At the end of each exercise with the NGMH, the participant was briefly questioned about his experience with the machine. Any evaluative comment made by the user was recorded, as were suggestions for improving it. The observer also noted important events or noteworthy differences in operating style during the task, and then briefly questioned the participant about problems with the system and reactions to the control system set-up for that task. Comments were recorded in a logbook for later review and analysis.
Involvement of Human Subjects: Human subjects were involved as described in the preceding paragraphs. In addition, the research subjects received a pre-test briefing outlining the conditions for their participation and testing conditions. The former included receipt of and explanation of the informed consent form reproduced elsewhere in this report. Research subjects also participated in a post-testing debriefing.
Project Identifier: ORNL-95-45
Project Title:
Physiological Responses to EMF (Electric and Magnetic Fields) in Humans
Principal Investigator:
Dr. Paul C. Gailey
Project started in: 1995
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project did not use human subjects in Fiscal Year 1998.
Explanation:
Task 3 data collection was completed in FY97
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: August 01, 1998
Number of Human Subjects who participated in this project/protocol during
08/01/97 - 08/01/98: 0
Type of Human Subjects Involvement:
This research was to investigate the possible effects of exposure to power-frequency magnetic fields on established measures of human physiology and performance. The aim of this task was to determine whether changes in magnetic field characteristics have a direct influence on human biological systems. In a previous study of 13 volunteers, the direct effects of variations in selected magnetic field amplitudes and frequencies on measures of brain electrical activity (EEG) was investigated. Exposure appeared to have differential effects on the EEG recorded from the visual areas of the brain, compared to the same measures obtained from scalp sites over the temporal areas. Additional studies on 50 healthy men and women volunteers were completed in FY 97. The volunteers are exposed to 60-Hz, 200mG intermittent magnetic fields for 90 minutes and then sensors were attached to standard scalp sites to record the EEG activity. Data analysis was completed on 25 men and women in FY 98. More extensive analysis are ongoing to identify possible electrophysiological responses to exposure at selected combinations of orientation, amplitude, and rate-of-change compared to control conditions.
No human subjects participating in this project were exposed to ionizing radiation or radioactive substances. The risks to human subjects participating was minimal. The intermittent exposure protocol was used in the laboratory in many previous studies with no adverse effects. The duration of the exposure was brief, and field strength levels were similar to those encountered in the home and work environment.
Project Identifier: ORNL-96-53
Project Title:
Survey of Personal Magnetic Field Exposure
Principal Investigator:
Dr. Paul C. Gailey
Project started in: 1996
This project ended in Fiscal Year 1998.
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project used human subjects in Fiscal Year 1998.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: August 14, 1997
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 1,000
Type of Human Subjects Involvement:
The objective of the pilot study (Phase I) of the project was to develop survey methodologies to characterize magnetic field exposures of the general population. In the pilot study, 200 randomly selected people were recruited by telephone. A follow-up phone call answered any questions about using the meter and administered a questionnaire. A little more than 1000 people participated in Phase II. The following summarizes the study. Telephone numbers were randomly selected using list-assisted Random Digit Dialing (RDD) methodology. An introductory letter was sent to all persons corresponding to the selected numbers who were listed on telephone directories. The letters were followed up by telephone calls. Telephone calls were also made to households that were not sent an introductory letter. The respondent was interviewed in order to select and recruit a household member for possible participation in the survey. A Consent form and a letter that illustrated the reasons and modality of the survey were sent to all the people who had agreed to participate. The Consent form was to be signed by the participants (or their parents or guardians) and returned before measurements could be performed. Upon return of the signed Consent form, the participants were sent a package containing a personal meter, the instructions for the use of the meter, a small diary to be used to write the type of activities performed, a questionnaire, and a fifty dollar check for compensation for participating in the study. The personal exposure meter was of the size of a pager and could be clipped to a belt or placed in a pocket. For infants and toddlers, the meter was to be placed inside a teddy bear, to be worn as a backpack or kept near them for the day of the measurements. The participants wore or kept the meter with them for 24 hours from the moment they first activated the meter. Magnetic field values were recorded every 0.5 seconds. Summary statistics were stored in the meter's memory every ten minutes. The participants recorded the time when certain activities (at home not in bed, at home in bed, travel, work, or school) started or ended. After 24 hours of measurements, the meter was mailed back. The meter's data were transferred to a computer file. The information for the diary and from the questionnaire was transcribed in a computer database. The magnetic field exposure for the entire 24-hours was calculated using a special software developed for the meter. The meter's calibration was checked and the meters were prepared for new participants. A letter was sent to the participants with the results of their individual measurements.
In total, 1,012 meters with usable data were returned. Overall, 3,867 households were contacted, 1,796 persons were recruited by phone, 1,718 persons were sent a Consent form, 1,120 persons returned a signed Consent form, 1,079 persons were sent a meter, 1,050 meters were returned in time for inclusion of the data, and 1,012 meters had valid data. Based on the time and event data in the activity diary, the measurements in each data file were partitioned into the following categories: at home not in bed, at home in bed, at work, at school, during travel, and other.
Procedures to maintain confidentiality were followed. All participants were assigned a study identification number upon enrollment in the study. The master code key and the file with personal data were kept in a secure place. Information from this file was released on a per need basis to the technicians performing the measurements and conducting the interviews. Information derived from diaries, interviews, and exposure monitoring were added to a computerized data base by study identification number only. Personal identifying information was not included in analysis, summary reports, or publications.
The participants were fully informed on the purpose and requirements of the study. Written consent to participate was obtained from the participants. The participants were given a copy of their completed consent form, a copy of the Experimental Subject's Bill of Rights, and an information letter regarding the study. At their request, participants received a summary of their personal EMF exposure measurements by the meter they wore.
There are no potential human health hazards to human subjects associated with this project. The participants are not being subjected to any additional magnetic fields beyond what is already present in their home. No physically invasive procedures are included in this study. No additional hazard or physical stress is expected from wearing the personal magnetic field meters. There are no potential psychological, social, economic, or legal hazards associated with this project.
Project Identifier: ORNL-96-54
Project Title:
Development of Field Exposure Predictions Models
Principal Investigator:
Dr. Paul C. Gailey
Project started in: 1996
This project ended in Fiscal Year 1998.
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project used human subjects in Fiscal Year 1998.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: March 10, 1998
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 20
Type of Human Subjects Involvement:
In the past, the majority of theoretical modeling work that has been conducted for field sources may not be used directly to predict the field exposure a person experiences in the environment. Field exposure is determined by both the field sources and by the person's activities in the environment. The objective of the project is to develop a model for estimating EMF personal exposures of individuals or groups within the general population. Use of this model will quantify an individual's total exposure over all time periods or within specific general locations such as home or work. The pilot studies were conducted to test the validity of the model.
During FY 1998 activity and source field levels for time weighted average (TWA), peak and harmonic models were assigned in the home environment. Both point estimated and probability distributions were selected for various components. The probability distributions were integrated into the baseline categories for TWA exposure in the home environment and simulations of exposure were performed. Preparation was made for additional pilot studies in the work environment. Specific sources in the work environment that were the subject of specific questions were identified. The U.C. Berkeley Human Studies Committee granted final approval for the pilot study protocol on March 10, 1998. The Survey Research Center performed the pilot studies of the questionnaire during April and May of 1998. Protocols and training of interviewers were provided by T. Dan Bracken, Inc.
The pilot studies consisted of 20 subjects: 10 working adults and 10 non-working adults. Within each of these two groups, five persons kept a diary and five did not. After wearing PE meters for a 24-hour period, the subjects were interviewed retrospectively about how and where they spent their time and the sources they used or were near. The interviews lasted less than 45 minutes. EMDEX II meters were used to measure TWA, peak and harmonic exposures. This design allowed models to be constructed from diaries and the retrospective questionnaires. The estimates from these models were compared to the observed measurements. These comparisons constituted an evaluation of the modeling capabilities developed by this project.
Procedures to maintain confidentiality were followed. All participants were assigned a unique identifiable number. The identifying information that links subjects to their data was accessible only to the PI of the pilot studies. Exposure measurement data and questionnaire data was identified by only the study identification number. Upon completion of the data analysis, the codes linking subjects to their data will be destroyed. The participants were fully informed on the purpose and requirements of the project prior to their participation. Written consent forms and explanatory material was presented to them.
There are no potential human health hazards to human subjects associated with this project. The participants are not being subjected to any additional magnetic fields beyond what is already present in their home, school, or work. No physically invasive procedures were included in the study. No additional hazard or physical stress is expected from wearing the personal magnetic field meters. There are no potential psychological, social, economic, or legal hazards associated with this project.
The current project is in the completion stage, and the final report will be forwarded to the ORAU/ORNL Committee on Human Studies by the end of FY 1998.
Project Identifier: ORNL-96-55
Project Title:
Environmental Tobacco Smoke: Composition, Exposure, and Measurement
Principal Investigator:
Dr. Roger A. Jenkins
Project started in: 1996
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project did not use human subjects in Fiscal Year 1998.
Explanation:
ORNL-55 is a new project. Planning work was initiated on Task 3 (see abstract) of ORNL-55 in FY97, but due to work in ORNL-17 , protocols and interview scripts are not likely to be worked out before the end of FY 98.
Funding Sources:
FY98 funding to be used for planning associated with human studies efforts of task 3 in ORNL-55. No subjects are expected to be contacted or recruited in FY98.
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: August 01, 1998
Number of Human Subjects who participated in this project/protocol during
08/01/97 - 08/01/98: 0
Type of Human Subjects Involvement:
Objectives
Task 1. To determine the personal exposure of non-smokers to environmental tobacco smoke in private residences and during sleep periods.
Task 2. To determine the nature of extremely low levels of measured nicotine in natural environments.
Task 3. To determine spousal smoking history for those subjects in the previous 16-Cities study (ORNL-17) living with smoking spouses.
Methodology
Task 1
Subjects will be recruited within a 50 mile radius of ORNL from the general population. Saliva samples will be collected in sterile Salivettes®, and analyzed by radio-immune assay or other appropriate analytical technique for cotinine, a major metabolite of nicotine. Salivary cotinine levels will be employed to determine the accuracy of self-reported smoking status.
Subjects will wear personal sampling pumps to collect an air sample from the subject's breathing zone. The sampler will remain on the subject during waking residential periods, and be placed at his/her bedside during sleep hours. Breathing zone samples will be gathered from the subjects on a daily basis, and analyzed for environmental tobacco smoke (ETS) constituents. Demographic and other personal information will be collected through interviews with ORNL staff, or through direct questionnaires.
Task 2
ORNL non-smoking staff volunteers (approximately 20) who reside in non-smoking homes will be utilized to collect 24-hour time weighted average (TWA) breathing zone samples, using the systems and analytical methods described in Task 1. Subjects will go about their daily routines, avoiding environments where smoking is occurring. Saliva samples will be collected and analyzed as described above. In this case, salivary cotinine will be examined and compared with the observed exposures to ETS nicotine to determine any potential relationship. Subjects will collect observational information, and will provide information regarding dietary intake of certain foods, which may influence salivary cotinine levels.
Task 3
An attempt will be made to contact all of the participants in the 16-Cities ETS Exposure Study (ORNL-17) who resided with smokers at the time of the study, using name and address information provided by the subjects during that study. This would involve potentially 243 subjects from the previous study. The subjects will be re-interviewed over the telephone regarding the smoking history of their spouses.
Exposure of Human Subjects
Human subjects are not exposed to any experimental atmospheres, or anything else that they would not encounter in their daily occupational or non-occupational routines. The purpose of the investigation is to determine the extent of natural exposure to ETS.
Involvement of Human Subjects
Procedures
Two aspects of these studies qualify them for human studies consideration. First, a sample of saliva will be acquired from each subject upon the entrance into and departure from the study. Depending on timing, sample acquisition could be as little as 24 hours or as much as 72 hours apart. The purpose of the saliva collection is to determine the concentration of a nicotine metabolite (cotinine) present. Salivary cotinine levels are used to confirm the absence of smoking among self reported non-smokers, and to determine the potential efficacy of use of salivary cotinine as a quantitative indicator of ETS-nicotine exposure. Saliva samples will be used for no other purposes.
Secondly, a great deal of demographic and exposure information is gathered on the subjects, which could not be collected via normal observation of the subjects. The confidentiality of the subjects is protected by several measures. First, subjects are assigned an identification number when they enter the study. The only place where the subject's name and address is tied to the identification number is on the written questionnaires which they complete. These questionnaires are stored in files maintained at ORNL in a restricted access area. A contractual requirement of any firm sub-contracted to recruit subjects or assist with field operations is that they make no permanent copies of the written questionnaires. In no place on the electronic data bases developed for the study are the subjects identified by anything other than a participant identification number.
Risks
Risks to the subjects are minimal. Subjects are asked to partake in normal activities, and are cautioned against wearing the sampling pumps around heavy machinery or during other activities in which wearing the sampling pump may compromise their safety. Subject names and addresses are only stored in hard copy (no electronic copy) in a restricted access area (combination lock access). Subject confidentiality are protected through the use of pseudo-identifiers. Acquisition of saliva samples is minimally invasive, and amounts to having to chew on a sterile piece of cotton dental dam for 60 seconds, and expelling it into a sterile vial.
Project Identifier: ORNL-98-47
Project Title:
Biomarkers of Magnetic Field Exposure (formerly Melatonin Levels of Electric Utility Workers)
Principal Investigator:
Dr. Paul C. Gailey
Project started in: 1998
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project used human subjects in Fiscal Year 1998.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Expedited
Most Recent Approval: May 07, 1998
Number of Human Subjects who participated in this project/protocol during
05/07/98 - 05/07/99: 16
reactivation of an previously approved protocol
Type of Human Subjects Involvement:
I. Objectives of Study:The goal of this project is to evaluate ornithine decarboxylase (ODC) activity and host immune cells (immunophenotyping of T cells, B cells and NK cells) in a group of 40 male electric utility workers exposed to different levels of magnetic fields. Individual magnetic field exposures will be quantified over three 24 hours work days and divided into work, sleep and other, non-work intervals. ODC activity will be measured in resting peripheral blood lymphocytes and lymphocytes exposed for three days to three different mitogens: PHA, PWM and superantigen. Total and differential blood counts as well as immunophenotyping including: total T and B cells (CE3+ and CD45+), subpopulation counts: T cells (helper/CD4+ and suppressor/cytotoxic/CD8+) and NK cells (CD56+) will be evaluated using the same blood sample.
II. Methods of Procedure: A group of 40 electric utility workers exposed to high fields (linemen, substation workers, power plant operators) and exposed to lower fields (utility maintenance, for example) will be evaluated in this study. Colorado State University will quantify individual magnetic fields over three 24 hours work days. Blood will be collected on the third day, between 4:00 and 6:00 p.m., at the participant's workplace, and then sent via Federal Express directly to Biophage, Inc., where the evaluation shall be conducted. Moreover, blood will be collected from 20 healthy adults from Laval, Quebec (age and sex-matched) at precisely the same time of the day. This population of utility workers is currently being assessed by Drs. Reif and Burch (Colorado State University) under a grant from the National Institutes of Environmental Health Sciences, so there are no additional costs to DOE for the sampling of workers. This work is a follow up to research originally supported by DOE, Office of Program Management.
With the exception of a review of immune parameters based on a consulting physician's guidelines, the participant's records shall be kept strictly confidential. All files will be maintained in a locked and secure manner at the Colorado State University Department of Environmental Health, accessible only to authorized personnel. Neither the participant's name or the results will be released to any private party, employer, or insurance company. The results of this study shall be released as group data only. There will be no means of identifying any particular participant in any results that will be published.
The participant shall be fully informed of the purpose and requirements of the study. Written consent to participate shall be obtained from the participants. The participant shall be given a copy of his/her completed consent form. If the results of the participant's blood test are outside normal ranges, the participant will be contacted by letter from Colorado State University Department of Environmental Health, advising the participant to contact his/her personal physician.
III. Possible Hazards and their Evaluation: Risks associated with blood sampling include possible hematoma (bruise), slight risk of infection, local soreness, and fainting. A certified nurse will be used to collect the sample and all precautions will be taken to insure the participant's safety.
IV: Radioisotopes and New Drugs/Devices: This study involves no use of radioisotopes or new drugs and devices.
Project Identifier: ORNL-98-52
Project Title:
Physiological Responses to Electric and Magnetic Fields in Humans (formally ORNL-97-ORNL-52 in FY97 database)
Principal Investigator:
Dr. Paul C. Gailey
Project started in: 1998
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project used human subjects in Fiscal Year 1998.
Funding Sources:
Project involves use of multiple protocols/subprojects.
Number of protocols/subprojects associated with this project: 4
Protocol/Subproject # 1
Protocol/Subproject Identifier: Task 5
IRB Review:
Type of Review: Full Board
Most Recent Approval: August 01, 1998
Number of Human Subjects who participated in this project/protocol during
08/01/97 - 08/01/98: 5
Type of Human Subjects Involvement:
Task 5: Adaptation of Heart Rate Variation (HRV) Over Multiple Exposures.
The objective is to perform a human exposure study to determine: (1) whether multiple nights of exposure result in adaptation of HRV; and (2) whether measures of heart rate taken during the day show altered variability as a function of night-time exposure.
Thirty healthy young men aged 21-35 participated in the study (25 in FY97 and 5 in FY98). Volunteers were recruited from local colleges, universities, and research institutes, and screened to assure that they were in good health (not on medication, no chronic disease or disability, no recent serious acute illness, regular sleep habits, no night work). After receiving a complete explanation of the procedures, risks and benefits of participation, they provided written informed consent. Subjects were matched on age, and body size, and one member of each matched pair was randomly assigned to the exposure condition; the other was assigned to the sham control condition; ( 15 men in each condition). Exposure was to the same intermittent, 200 mG, circularly polarized magnetic field used in the previous studies. Under the intermittent exposure protocol, the field was presented from 11 pm to 7 am in alternating l-hr field-off and field-on periods. During field-off periods, the equipment was not energized. During field-on periods, the field cycles on and off at 15-seconds intervals. The study was performed double-blind to control for the effects of expectation.
Each subject slept in the exposure facility at Midwest Research Institute (MRI) on four consecutive nights. During the days surrounding the exposure nights, the subject wore two small portable monitors (Holter and Emdex II) to measure heart rate and ambient magnetic field exposure while performing daily activities. Urine samples were obtained before and after each night sleep period, and blood samples (14 mL each) were obtained via venipuncture before and after each night sleep periods. As in the previous studies, recording sensors were attached to the chest, used to measure cardiac interbeat interval. Heart rate data collected during the day was downloaded from the portable monitors. Magnetic field exposure data collected during the day was also downloaded from the monitors.
Data collection was completed on 30 healthy young men (25 in FY97 and 5 in FY98), and no unusual problems with the facility or the test protocol were experienced. Statistical analysis and data reduction are currently underway and will be completed by the end of FY98.
Risks to subjects in this study are minimal. Bruising and soreness sometimes occur with venipuncture; this will be prevented in so far as possible by using a highly trained, experienced phlebotomist/medical technologist to perform the venipuncture. Repeated application of recording sensors to the chest for measuring heart rate can sometimes result in skin irritation. To reduce this possibility, potential volunteers with known allergies to tape or other adhesives will not be included in the study. Furthermore, the sensors will not be applied to identical sites on sequential days or nights. It is feasible to do this, as the Lead II electrocardiogram we will collect as basic data can be obtained from several site configurations. Wearing a Holter monitor to record heart activity while going about one's daily activities is a standard medical practice and presents no health risk. Similarly, wearing an Emdex meter to record magnetic field exposure during daily activities is a widely used technique in occupational studies within the electric utility industry and in residential studies and presents no health risk.
IRB Review:
Type of Review: Full Board
Most Recent Approval: August 01, 1998
IRB Approval Number: ORNL-52
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 12
Type of Human Subjects Involvement:
Task 6: Heart Rate Variation (HRV) in Women During Magnetic Field Exposure
Twelve healthy young women aged 21-35 will participate in the study. They will be recruited and screened as in Task 5. Additional screening criteria for women volunteers will include: regular and predictable menstrual cycle (26-32 days), not on hormonal birth control, and not pregnant. Informed consent will follow those of Task 5. Subjects will be matched on age, and body size, and one member of each matched pair will be randomly assigned to the Task 5 exposure condition; the other will be assigned to the sham control condition (6 women in each condition). All women will be tested between days 2 and 8 of the menstrual cycle to control for hormonal effects, and the study will be performed double-blind to control for the effects of expectation. Each subject will sleep in the exposure facility at Midwest Research Institute (MRI) on four consecutive nights. During the days surrounding the exposure nights, the subject will wear the portable monitors to measure heart rate and ambient magnetic field exposure. Urine samples will be obtained before and after each night sleep period, and blood samples (14 mL each) will be obtained via venipuncture before and after the first and last sleep periods. As in Task 5, recording sensors attached to the chest area will be used to measure cardiac interbeat interval. We believe the risks to subjects in this task are minimal. The possible hazards are the same as in Task 5, and the same precautions will be taken to minimize possible problems.
IRB Review:
Type of Review: Full Board
Most Recent Approval: August 01, 1998
IRB Approval Number: ORNL-52
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 24
Type of Human Subjects Involvement:
Task 7: Heart Rate Variation (HRV) In Middle-Aged Men During Magnetic Field Exposure
The objective is to study the effects of nocturnal magnetic field exposure on HRV using a sample of men 40-60 years old. Twenty-four men aged 40-60 yrs will participate in the study. Subjects will be recruited from local civic organizations, colleges, universities, research institutes, and the general community. They will be screened to assure that they do not have known cardiovascular disease, that they are taking no medications that might alter heart rate variability, and that they are not suffering from any chronic disease. Informed consent will follow those described for Task 5. Each subject will sleep in the MRI exposure facility two nights approximately one week apart. On one night, the subject will be exposed to the intermittent, 200 mG, circularly polarized field described above; on the other night, he will be sham exposed. Order of sham and exposure conditions will be counter balanced. Blood samples ( 14 mL each) will be obtained before and after each sleep period. Analysis of heart rate data will follow the same procedures described for Task 5.
The risks to subjects in this task are minimal. The study design is identical to that used in our previous three studies of magnetic field exposure effects on HRV in younger men. Potential risks associated with venipuncture, sensor application, etc. will be further minimized as described for Task 5.
IRB Review:
Type of Review: Full Board
Most Recent Approval: August 01, 1998
IRB Approval Number: ORNL-52
Number of Human Subjects who participated in this project/protocol during
FY 1998 (10/1/97 - 9/30/98): 18
Type of Human Subjects Involvement:
Task 8: Exposure Frequency and Heart Rate Variability (HRV)
In previous research conducted at MRI, measures of heart rate variability (HRV) were influenced by magnetic field exposure at one amplitude (200 mG), but not at a lower amplitude (10 mG), suggesting that the underlying mechanisms involved in this interaction may be threshold dependent. The objective is to determine whether measures of HRV show threshold sensitivity in relation to variations in magnetic field exposure frequency. Eighteen male volunteers aged 21-35 will participate in a study to evaluate the effects of magnetic field exposure at three frequencies (A= 1 6Hz, B= 40Hz, C=60Hz) compared to sham control conditions. Volunteers will be recruited from local colleges, universities, and research institutes, and screened to assure that they are in good health (not on medication, no chronic disease or disability, no recent serious acute illness, regular sleep habits, no night work). Each volunteer will provide written informed consent. Subjects will sleep overnight In the MRI exposure test facility. Between midnight and 6 am, the intermittent 200 mG magnetic field used in previous MRI studies of HRV will be presented in alternating l-hr field-on and field-off periods. Nine of the 18 subjects selected at random will be exposed to the 16Hz test frequency during all field-on hours; the remaining nine subjects will be exposed to the 40Hz test frequency during the field-on hours. The study will be performed double-blind to control for expectation effects. Risks to subject in this task are minimal. Potential risks associated with sensor application will be further minimized as described for Task 5.
Project Identifier: ORNL-98-56
Project Title:
Study of Neurotransmitters in Children with ADD or ADHD
Principal Investigator:
Dr. Gary A. Sega
Project started in: 1998
Project Funding Information:
Project did not receive funding in Fiscal Year 1998.
Project did not use human subjects in Fiscal Year 1998.
Explanation:
This is a pilot project. No application has been submitted requesting grant funding.
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Expedited
Most Recent Approval: June 12, 1998
Number of Human Subjects who participated in this project/protocol during
the Last Reporting Period for this Project: 0
Type of Human Subjects Involvement:
Attention Deficit Disorder (ADD) and Attention Deficit Hyperactive Disorder (ADHD) are two subtypes of the most frequent behavioral disorders observed in school age children. It is estimated that 2 to 4 percent of these children are affected and that 8 times more boys than girls show the symptoms. The disorder is characterized by inattention, excessive motor activity, impulsivity and distractibility. These disorders have a strong familial predisposition with 28.6% of biological parents having a history of hyperactivity (Biederman, et al., 1990). Twin studies showed 81 % concordance for monozygotic twins and 29% for dizygotic twins, demonstrating a moderate to high heritability (Stevenson 1992). Studies on cerebral glucose metabolism by PET scanning have shown a significant reduction in glucose metabolism in 30 to 60 specific regions of the brains in hyperactive adults who were parents of hyperactive children (Zametkin et al., 1990). A review of the genetics of ADHD and autism was recently published by Smalley (1997) and the polygenetic inheritance involving genes that effect dopamine, serotonin and other neurotransmitters was reviewed in the whole spectrum of childhood behavioral disorders by Comings (1997).
The medications which are known to be effective in the treatment of ADHD (Greenhill 1992) include methylphenidate (Ritalin), dextroamphetamine (Adderall, Dexedrine), and Pemoline (Cylert). These drugs are inhibitors of the dopamine transporter. Cook et al., (1995A) found an association of the gene for the dopamine transporter locus (DAT1) in children diagnosed with ADHD. LaHoste et al., (1996) found variability in the length of a region of the dopamine D4 receptor in children with ADHD. This receptor is preferentially distributed in the cortical and limbic regions of the brain and the expanded repeats have been shown to mediate a blunted intracellular response for dopamine. The changes in dopamine metabolism due to mutations in the dopamine receptor gene or the dopamine transporter gene may be contributing factors in the expression of the symptoms associated with ADHD. Changes in the metabolism of other neurotransmitters such as serotonin have been observed in children with ADHD and other associated behavioral disorders including conduct disorder (CD) and/or oppositional defiant disorder (ODD). A positive correlation was also found between 36 children with disruptive behavior disorders and their biological mothers (Cook et al., 1995B).
The purpose of the proposed research is to investigate the blood levels of the following neurotransmitters: dopamine, serotonin, and serotonin to tryptophane ratio and melatonin in children with ADHD diagnosed according to the DSM-III-R criteria. A comparison of the levels prior to treatment and after treatment for several weeks or months is planned to determine if any correlations can be established between the response to treatment and the levels of neurotransmitters prior to the beginning of treatment.
The children will be diagnosed by the principal investigator and the collaborating investigator, Dr. Virginia Frye following the DSM-III-R criteria. These children are referred to the Developmental and Genetic Center by area pediatricians and family physicians for consultation and recommendations concerning treatment. The psychomotor testing and behavior rating scales to be used are part of the clinical diagnosis and are not experimental research tools.
The blood will be drawn for clinical diagnostic tests and 1 or 2cc of extra blood will be used for the study of the neurotransmitters. This blood will be centrifuged and the plasma will be stored frozen at -70C until the samples are ready to be analyzed. The studies on the levels of dopamine, serotonin, serotonin to tryptophan and melatonin will be performed at the laboratory of Gary Sega at ORNL. Dr. Sega has performed preliminary studies in an experimental animal model (strain of mice with a specific genetic background) with behavioral findings of hyperactivity. He observed a decrease in the serotonin level in these mice compared to controls. Dr. Sega has many years of experience in research and a state-of-the-art laboratory for the analysis of many biomolecules in biological samples.
The specific objectives of this project are to gain knowledge on the neurobiological factors leading to the behavioral abnormalities observed in children with ADHD. The long-term goal is to define the metabolic changes and genetic mechanisms involved in the hope that this knowledge may lead to the development of more effective therapeutic interventions.