Ms. Pamela
S.
Bonee
Oak Ridge Institute for Science and Education/CPD
P.O. Box 117
Oak Ridge, TN 37831-0117
Phone: 865-576-3147
Fax: 865-241-2923
E-mail: boneep@orau.gov
Number of Human Subjects projects reported: 19
| ORAU-78-96 | "Use of Ca-DTPA and Zn-DTPA for Chelation Therapy of Heavy Metals" |
| ORAU-79-63 | "The U.S. Radiation Accident Registry Follow-Up Program" |
| ORAU-80-58 | "Whole Blood Procurement, Consent for Research Waiver Form and Payment Authorization" |
| ORAU-80-60 | "Comprehensive Epidemiology Study of Department of Energy Atomic Workers" |
| ORAU-80-61 | "The DTPA Registry Follow-Up Program" |
| ORAU-89-60a | "Amendment - Comprehensive Epidemiology Study of Department of Energy Atomic Workers: National Death Index" |
| ORAU-91-81 | "Use of Prussian Blue for Internal Decontamination of Radiocesium" |
| ORAU-91-83 | "Identification and Abstraction of Death Certificates for National Registry of Persons Exposed to Hazardous Substances" |
| ORAU-94-106 | "Department of Energy Epidemiologic Surveillance Data Center" |
| ORAU-99-87a | "Beryllium Workers Follow-up Study, Phase II: Screening for Beryllium Sensitivity and Definitive Diagnosis of Chronic Beryllium Disease. Amendment - to add Former Beryllium Workers at all DOE sites where Beryllium was used." |
| ORAU-00-108 | "Update of a Mortality Study of Titanium Dioxide Workers" |
| ORAU-03-PANTEX 1 | "Former Pantex Worker Medical Surveillance Program" |
| ORAU-04-126 | "Remote Deception Detection Using Volatile Chemical Emissions Research Project" |
| ORAU-04-127 | "Survey of Respiratory Symptoms Among Workers in the Forrestal Building" |
| ORAU-05-130 | "Message Testing for Prevention of Carbon Monoxide Poisoning Among Immigrants" |
| ORAU-05-131 | "DOE National Supplemental Screening Program" |
| ORAU-05-132 | "Formative Research: Testing of Pandemic Influenza Messages with the Public and Health Care Providers" |
| ORAU-05-81a | "Amendment: Use of NDA Prussian Blue for Internal Decontamination of Radiocesium (NDA)" |
| ORAU-05-96a | "Amendment: Use of Ca-DTPA and Zn-DTPA (NDA product) for Chelation Therapy of Heavy Metals" |
"Use of Ca-DTPA and Zn-DTPA for Chelation Therapy of Heavy Metals"
Principal Investigator: Dr. Patrick C. Lowry, Oak Ridge Associated Universities
Project started in: 1978
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: Oak Ridge Institute for Science and Education
Most recent approval: 11/09/04
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: 06/01/03 to 05/31/04
Explanation:
U.S. FDA Reporting Year.
Type(s) of Human Subjects Involvement:
Investigational new drug (IND) 4041, trisodium calcium diethylenetriaminepentaacetate (Ca-DTPA), and IND 14603, trisodium zinc diethylenetriaminepentaacetate (Zn-DTPA), are investigational new drug applications which are administered by Oak Ridge Associated Universities under contract with the U.S. Department of Energy. New supplies of DTPA have been imported from Heyl, GmBH in Berlin during this reporting period only for the Strategic National Stockpile (SNS), Centers for Disease Control and Prevention. Radiation Emergency Assistance Center/Training Site (REAC/TS) and co-invesitgators in the study did not receive new DTPA during this reporting period. Both Ca- and Zn-DTPA are approved by both the U.S. Food and Drug Administration (FDA) and DOE/Environment Safety and Health and meet the chemical specifications of the U.S. Pharmacopeia (USP 23) and that of the European Union (Pharm. Eur.) Ca- and Zn-DTPA have recently (late in the reporting period) been classified by the U.S. FDA as New Drug Application (NDA) and are no longer considered investigational drugs (INDs). This project will deal only with IND product, at this point held only by SNS and REAC/TS, and is expected to be used only in times of national emergency, when NDA product is deleted and can not be rapidly replaced.
DTPA belongs to the group of synthetic polyamino polycarboxylic acids which form stable complexes (metal chelates) with a large number of metal ions, especially the transuranic elements. The drug effectively exchanges calcium or zinc for another metal of greater binding power and carries it to the kidneys where it is then excreted. Historically, in the DOE laboratory complex, DTPA has been quite successful in promoting urinary excretion of the actinide elements in accident situations where inhalation or systemic uptake through wounds was involved.
Ca-DTPA is approximately 10 times more effective than Zn-DTPA for the initial chelation of transuranic elements. Therefore, Ca-DTPA should be used whenever larger body burdens of transuranics are involved. Ca-DTPA is the drug of choice for initial patient management of internal contamination with transuranic elements unless contraindicated. After approximately 24 hours, however, Zn-DTPA is, for all practical purposes, as effective as Ca-DTPA. This comparable efficacy, coupled with its lesser toxicity, makes Zn-DTPA the preferred agent for protracted therapy. The effectiveness of chelation therapy is highly dependent not only on the metal itself, but also on the chemical and physical characteristics of the compound at the time of DTPA administration. Because the efficiency of chelation decreases with time, DTPA ideally should be given within six hours of exposure.
Accidents involving internal contamination with the actinide elements (Pu, Am, Cm) occur in the DOE complex and both Ca-DTPA and Zn-DTPA have proven effectiveness in the medical management of these cases. Anyone in the DOE system or elsewhere with internal exposure to actinides (Pu, Am, Cm, etc.) is eligible for treatment with Ca-DTPA and Zn-DTPA. Most cases of internal contamination involve inhalation of the material, but uptake through wounds has occured in some reporting periods.
One case involving use of DTPA is recorded on the REAC/TS registry for this reporting time period. This case involves potential internal contamination through inhalation of a contaminant which contained 96 percent Pu-238, 3 percent Pu-239, and trace amounts (<1 percent) of U-238, Np-237, Am-241 and Cm-244. There was also skin contamination to both palms and to the mouth area. No contamination was noted in the anterior nares.
After completing the standard consent form, the skin contamination was cleared with GoJo Wipes and soap and water. One dose of Ca-DTPA with diluent was administered. No changes in blood pressure or vital signs were noted. No adverse effects were noted. Urine biodosimetry revealed some Pu (report incomplete). Complete blood count revealed relatively low absolute lymphocyte count (ALC), but count was noted to be consistant with the patients previous ALC and was considered normal.
No serious toxicity in human subjects has been reported as a result of 641 separate patients administered DTPA (either intravenously by slow iv push, by intermuscular injection, or by nebulizer) in recommended doses for a total of 4,681 separate doses current through the reporting period (the one case where DTPA was use for external decontamination is not included in the totals). In addition, no serious adverse effects have been noted as a result of over 1,000 doses of Zn-DTPA in the recommended dosage given to individual subjects. The project is approved by the Oak Ridge Site-wide IRB, which also has addressed privacy issues related to this project.
"The U.S. Radiation Accident Registry Follow-Up Program"
Principal Investigator: Dr. Patrick C. Lowry, Oak Ridge Associated Universities
Project started in: 1979
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Identifier or number: 63
Institutional Review Board (IRB) Review:
Type of Review:
Full Board
Approving Institution: Oak Ridge Institute for Science and Education
Most recent approval: 11/09/04
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Fiscal Year 2005
Type(s) of Human Subjects Involvement:
The Radiation Emergency Assistance Center/Training Site (REAC/TS) Accident Registry is an invaluable historical resource for research into the mechanisms of radiation accidents, as well as a useful compilation of biochemical data collected during medical management of these cases. In many cases, we have complete accident reconstruction, human factors data, medical and laboratory data, patient history transcribed from a live interview at REAC/TS, and multiple kinds of health physics data. This database is an invaluable resource for DOE and other governmental agencies interested in the human factors aspects of radiation-induced injury.
One of the most important aspects of medical management of a radiation accident is early dosimetry information. However, in many cases, both the magnitude of the accident and the dosimetry profile(s) of the victim(s) are not known for days to weeks. Data from the REAC/TS Accident Registry were recently used to develop an early dose assessment algorithm for high-level gamma accidents. This algorithm (Goans et al, Health Physics 72(4): 513-518, 1997) provides a simple dose-estimation algorithm based on lymphocyte kinetics from prior radiation accidents. In FY2001, this work was extended to encompass criticality accidents (Goans et al, Health Physics 81(4): 446-449, 2001). These papers represent excellent examples where retrospective analysis of accidents has been used to further the medical treatment of future cases.
In FY2002 to 2004, the U.S. FDA almost exclusively used data from the REAC/TS radiation registry and the DTPA registries as a basis for moving Ca- and Zn-DTPA from an investigational new drug (IND) to a New Drug Application (NDA) classification, allowing more general accessability to DTPA for the general medical community.
In FY2005, no radiation accidents were reported to REAC/TS. Up to September 30, 2005 the REAC/TS Accident Registry contained data on 2,177 events involving approximately 133,802 individuals. The U.S. Radiation Accident Registry currently contains medical and health physics data on 134 radiation-related fatalities (26 U.S. accidents, 100 non-U.S. accidents, eight location of accident not noted, likely due to record error precomputerization), and 428 radiation accidents involving 3,050 significant exposures.
As usual, the response from REAC/TS continues to occur through interaction directly with the private sector, through all aspects of the DOE system, various state and foreign agencies, and with the Nuclear Regulatory Commission (NRC).
An individual's consent to participate in the Radiation Accident Registry/follow-up program is obtained by the co-investigator/physician at the time of the accident. Entry into the Radiation Accident Registry/follow-up program is based on ERDA/NRC/DOE established criteria. All data collected for the Registry will be encoded and entered into the password-protected computerized data bank maintained at ORAU as part of the DOE Record System as described in the Federal Register. The information contained in the Registry is extracted from individual records which are retrievable only by REAC/TS staff by name or other personal identifier. The information, therefore, is included in a DOE Privacy Act system of records and will not be disclosed to third parties without written consent of the participant. Written consent for approved epidemiological research studies using redacted (no identifiers) records is obtained from registry participants at the same time informed consent is obtained.
"Whole Blood Procurement, Consent for Research Waiver Form and Payment Authorization"
Principal Investigator: Dr. Donna L. Cragle, Oak Ridge Institute for Science and Education
Project started in: 1980
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: Oak Ridge Institute for Science and Education
Most recent approval: 11/08/04
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 35
Reporting period for number of human subjects:
Fiscal Year 2005
Type(s) of Human Subjects Involvement:
The objectives are to define the range and variability in the proliferative response of human lymphocytes to in vitro exposure to beryllium salts. This specific study involves blood samples from control persons who have never been at risk for exposure to beryllium in the workplace. The results from this testing are used to establish the range of values for a normal test and to identify the cut-off values to be used in identifying abnormal tests in beryllium-exposed workers. Standard laboratory methods for separating and culturing cells are used. The only procedure that directly involves the blood donor is the venipuncture that is used to collect the blood sample. The only risks anticipated are the minor bleeding at the site of the venipuncture.
The purpose of the lymphocytes drawn on healthy individuals is to provide control cells for beryllium sensitization studies only and are not used as part of any protocol that involves human subjects. The consent form is provided and payment authorization is obtained by laboratory personnel. The results of the tests are stored only under a laboratory identifier code. There is no link between the volunteers and the laboratory codes. Aggregate results are used to set the normal values for each new lot of serum used in the laboratory.
During FY2005, six new serum lots were tested and two were chosen for further use in the laboratory.
"Comprehensive Epidemiology Study of Department of Energy Atomic Workers"
Principal Investigator: Dr. Donna L. Cragle, Oak Ridge Associated Universities
Project started in: 1980
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Full Board
Approving Institution: Oak Ridge Institute for Science and Education
Most recent approval: 11/08/04
IRB approval number: 60
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Fiscal Year 2005
Type(s) of Human Subjects Involvement:
ORISE supports the DOE Office of Health Programs and the National Institute for Occupational Safety and Health (NIOSH) in a number of activities utilizing retrospective occupational records located at various DOE facilities.
These activities include:
1. Compiling rosters of workers from hard-copy records.
2. Collecting death certificates for DOE worker populations; coding causes of death and entering codes to computer files.
3. Scanning original facility documents for NIOSH use in worker studies.
4. Analyzing cause of death data with respect to exposure level using standard dose-response methodology.
5. Analyzing cause of death data in a descriptive manner.
During FY2005, there was no activity.
"The DTPA Registry Follow-Up Program"
Principal Investigator: Dr. Patrick C. Lowry, Oak Ridge Associated Universities
Project started in: 1980
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: Oak Ridge Institute for Science and Education
Most recent approval: 11/09/04
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: 06/01/03 to 05/31/04
Explanation:
FDA reporting year
Type(s) of Human Subjects Involvement:
The purpose of the DTPA Registry Follow-up Program is to document cases where diethylenetriaminepentaacetate (DTPA) is used, both in the DOE complex and elsewhere in the U.S., to document drug safety and efficacy and to maintain a comprehensive registry of medical information in these cases for both the DOE and the FDA. Ca-DTPA and Zn-DTPA are distributed by Oak Ridge Associated Universities (ORAU) under contract with the U.S. Department of Energy.
No new supplies of either Investigational New Drug (IND) Ca- or Zn-DTPA for the Radiation Emergency Assistance Center/Training Site (REAC/TS) or its co-investigators have been imported from Heyl, GmBH in Berlin during this reporting period. A shipment of New Drug Application (NDA) DTPA was received and distributed to co-investigators. All Ca- and Zn-DTPA held by co-invesitgators are NDA and are not considered by the Food and Drug Administration (FDA) as "investigational drugs." They are approved by the U.S. FDA, supported by DOE/EH, and meet the chemical specifications of the U.S. Pharmacopeia (USP 23) and that of the European Union (Pharm. Eur.).
DTPA belongs to the group of synthetic polyamino polycarboxylic acids which form stable complexes (metal chelates) with a large number of metal ions, especially the transuranic elements. The drug effectively exchanges calcium or zinc for another metal of greater binding power and carries it to the kidneys where it is then excreted. Historically, in the DOE laboratory complex, DTPA has been quite successful in promoting urinary excretion of the actinide elements in accident situations where inhalation or systemic uptake through wounds was involved.
One case involving use of DTPA is recorded on the REAC/TS registry for this reporting time period. This case involves internal contamination through inhalation of a contaminant which contained 96 percent Pu-238, 3 percent Pu-239, and trace amounts (<1 percent)of U-238, Np-237, Am-241, and Cm-244. There was also skin contamination to both palms and to the mouth area. No contamination was noted in the anterior nares.
After completing the standard consent form, the skin contamination cleared with GoJo Wipes and soap and water. One dose of Ca-DTPA with diluent was administered. No changes in blood pressure or vital signs were noted. No adverse effects were noted. Urine biodosimetry revealed some Pu (report incomplete). Complete blood count revealed relatively low absolute lymphocyte count (ALC), but count was noted to be consistant with patients previous ALC and was considered normal. F/u dosimetry results have not been obtained to date.
No serious toxicity in human subjects has been reported as a result of 641 separate patients administered DTPA (either intravenously by slow iv push, by intermuscular injection, or by nebulizer) in recommended doses for a total of 4,681 separate doses current through the reporting period (the one case where DTPA was use for external decontamination is not included in the totals). In addition, no serious adverse effects have been noted as a result of over 1,000 doses of Zn-DTPA in the recommended dosage given to individual subjects. The project is approved by the Oak Ridge Site-wide IRB, which also has addressed privacy issues related to this project.
The status of the REAC/TS DTPA Registry through June 2005 shows 27 active co-investigators throughout the country. Since the beginning of the Registry, 641 patients have received 4,682 doses of DTPA with an adverse reaction rate under 1.5 percent, mostly very minor. Our extensive documentation of DTPA usage therefore demonstrates the inherent safety of the drug. We feel that the REAC/TS DTPA Registry is a valuable resource for the medical follow-up of workers involved in accidents involving the transuranic elements.
The DTPA package inserts and the consent form have been modified to meet NDA product according to recommendations of the IRB, DOE/HQ, the FDA, and an independent review committee commissioned by the DOE. The consent form has been modified in FY2005. An individual's consent to participate in the DTPA Registry/follow-up medical program is obtained by the co-investigator/physician at the time of the initial DTPA treatment. All data collected for the Registry will be encoded and entered into the password-protected computerized data bank maintained at ORAU as part of the DOE Record System as described in the Federal Register. The information contained in the Registry is extracted from individual records which are retrievable only by REAC/TS staff by name or other personal identifier. The information, therefore, is included in a DOE Privacy Act system of records and will not be disclosed to third parties without written consent of the participant. Written consent for approved epidemiological research studies using redacted (no identifiers) records is obtained from DTPA registry participants at the same time informed consent is obtained, prior to first DTPA treatment.
"Amendment - Comprehensive Epidemiology Study of Department of Energy Atomic Workers: National Death Index"
Principal Investigator: Dr. Donna L. Cragle, Oak Ridge Institute for Science and Education
Project started in: 1989
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Full Board
Approving Institution: Oak Ridge Institute for Science and Education
Most recent approval: 11/08/04
IRB approval number: 60a
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Fiscal Year 2005
Type(s) of Human Subjects Involvement:
This project uses the National Death Index (NDI) to link death information to worker or special exposure populations. The NDI is a specialized source of death data. Death certificates retrieved under this protocol are maintained and shared under a restrictive set of rules set forth by the NDI.
During FY2005, this data source was not used. It is anticipated that there will be futures uses of the NDI.
"Use of Prussian Blue for Internal Decontamination of Radiocesium"
Principal Investigator: Dr. Patrick C. Lowry, Oak Ridge Institute for Science and Education
Project started in: 1991
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: Oak Ridge Institute for Science and Education
Most recent approval: 11/09/04
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Other: 06/01/04 to 05/31/05
Explanation:
U.S. FDA reporting period
Type(s) of Human Subjects Involvement:
Prussian Blue (ferric ferrocynate) is well studied as an ion-exchange resin which is quite efficacious in the decorporation therapy required for patients with high body burdens of radiocesium, radiothallium, or stable thallium. Anyone in the DOE system or with internal contamination with radiocesium, radiothallium, or stable thallium is eligible for treatment with Prussian Blue. Those with internal contamination with radiocesium, radiothallium, or stable thallium elsewhere in the U.S. outside the DOE system are also eligible with DOE approval for treatment if Prussian Blue is not available. Although technically Prussian Blue, under New Drug Application (NDA), should be widely available, there are many locales in the U.S. where it is not immediately available.
There has been no use of Prussian Blue for internal contamination with either radiocesium, radiothalliumin, or stable thallium in the most recent reporting period (6/1/04 to 5/31/05).
ORAU-81, Use of Prussian Blue for Internal Decontamination of Radiocesium and Thallium, has been granted by the Food and Drug Administration's (FDA) Investigational New Drug (IND) 51,700. Despite the approval of an NDA for Prussian Blue to Heyl GmBH, the IND for Prussian Blue is planned at this time to continue but the project remains an inactive. The project will continue in the DOE community using NDA drug (see admendment July 20, 2005). A supply of Prussian Blue, obtained from the German company Heyl GmBH, is currently distributed to six co-investigators in the DOE complex. This product, although manufactured by Heyl under the IND, has been determined to meet NDA standards and the FDA has authorized ORISE in writing to use the product of Batch # 014082 as NDA quality product. Therefore all Prussian Blue now with co-investigators is from this batch and so can be treated as NDA product.
Prussian Blue is to be used in the U.S. DOE complex as a decorporation agent for patients internally contaminated with medically significant amounts of radiocesium and radiothallium. In this document, the name Insoluble Prussian Blue (PB) without further specification indicates the following compound: Ferric(III) hexacyanoferrate(II) "insoluble PB," Fe4 [Fe (CN)6]3, molecular weight: 859.3, Color Index No. 77.510, and CAS Registry No. 14038-43-8. Under the NDA (#58060-00201) Insoluble Prussian Blue is also known as Radioguardase. Insoluble Prussian Blue has been recommended for years as the drug of choice by national and international radiation protection societies for use in treating internal contamination with radiocesium. It was effectively used in the treatment of patients contaminated with Cs-137 in the 1987 Goiania, Brazil accident under temporary clearance by FDA for "compassionate use" by the ORAU's REAC/TS program.
Prussian Blue is distributed by the Oak Ridge Institute for Science and Education (ORISE) to DOE co-investigators for DOE facilities throughout the country. Up until July 20, 2005, Prussian Blue was distributed under the IND. After the amendment for Project 81 of July 20, 2005, it is not available as IND but is as NDA product at DOE facilities participating in the ongoing safety and efficacy study (ORAU 91-81). As an NDA, Prussian Blue is technically available throughout the country from pharmacies with a physician's prescription. However, it is not generally available as yet and ORISE/REAC/TS with DOE approval can also provide limited amounts of Prussian Blue to non-DOE personnel.
ORISE is managed by Oak Ridge Associated Universities (ORAU), under contract with the U.S. Department of Energy (DOE). Insoluble PB, ferric hexacyanoferrate, Fe4[Fe(CN)6]3 is a drug that enhances excretion of isotopes of cesium and thallium from the body by means of ion exchange. It has had a long and successful history in the treatment of internal contamination with radiocesium. In the normal course of DOE operations, internal contamination with radioactive cesium is thought to be more likely than with radiothallium.
Of the various radioisotopes of cesium, Cs-137 is the most important. Cs-137 is a common fission by-product material, a frequent active component of sealed sources, and an important radionuclide in radiation oncology. The use of Cs-137 falls under the jurisdiction of the Nuclear Regulatory Commission (NRC). It is a ubiquitous radionuclide found throughout the DOE system and in hospitals performing either gynecological brachytherapy or interstitial therapy for solid tumors. Until the Goiania incident in Brazil, there were very few cases of radiocesium contamination requiring decorporation therapy. However, there is an increasing potential for such contamination to occur and a need for specific therapy. Additionally, given its widespread availability and its chemical characteristics, it is considered as a prime candidate for use in a terrorist event, such as a dirty bomb. The recent increase in workers performing remediation work at hazardous waste sites also requires that clinicians have Insoluble Prussian Blue available and understand the nature of its pharmacodynamics.
See amendment July 20, 2005 for more details.
"Identification and Abstraction of Death Certificates for National Registry of Persons Exposed to Hazardous Substances"
Principal Investigator: Dr. Elizabeth D. Ellis, Oak Ridge Institute for Science and Education
Project started in: 1991
This project ended in fiscal year 2005.
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Expedited
Approving Institution: Oak Ridge Institute for Science and Education
Most recent approval: 11/20/04
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Fiscal Year 2005
Type(s) of Human Subjects Involvement:
The objective is to determine vital status and retrieve hard-copy death certificates from states' vital records offices and electronic death information from the National Death Index (NDI) for individuals included in Agency for Toxic Substances and Disease Regisrty (ATSDR) disease registries. ATSDR provides identifying information and date and state of death information for individuals included in its registries. The Oak Ridge Institute for Science and Education (ORISE) matches this information against the Pension Benefits Information database to identify decedents and the NDI to retrieve death certificate and cause of death information. Based on data received from the NDI, requests are made to the states in which the deaths occurred for hard-copies of the death certificates. All electronic and hard-copy records are returned to ATSDR at the completion of project. Access to ATSDR data at ORISE is on a need-to-know basis. All research staff have signed confidentiality agreements as a condition of employment. All hard-copy records are kept in locked cabinets when not being used. Electronic files are accessed using a password. There was no activity on this project in FY2004.
"Department of Energy Epidemiologic Surveillance Data Center"
Principal Investigator: Dr. Elizabeth D. Ellis, Oak Ridge Institute for Science and Education
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:
Expedited
Approving Institution: Oak Ridge Institute for Science and Education
Most recent approval: 11/20/04
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 87699
Reporting period for number of human subjects:
Fiscal Year 2005
Type(s) of Human Subjects Involvement:
The purpose is to undertake regular and systematic collection, analysis, and interpretation of data on illness and injury in the DOE work force. The objectives are: determine rates of illness and injury among workers; identify increases in the risk of disease among workers; provide data in response to questions from workers, physicians, and others about possible occupational health effects; and identify areas in which further investigation or analytic studies should be initiated. This ongoing surveillance requires regular collection, maintenance, and interpretation of illness and injury, demographic, and job-related data. Electronic data submissions are received at regular intervals from the participating DOE sites. The data are placed in the epidemiological surveillance database where the data are evaluated for quality and completeness. Illness and injury data are nosologically coded. The data are processed into annual reports for each site that include characterization of the work force included in the epidemiological surveillance program at the site and an evaluation of the observed illness and injury trends at each site. All data used for epidemiological surveillance are routinely collected for other purposes. Data for individual workers are identifiable only by an encrypted number. Each participating site uses its own encryption algorithm. ORISE does not have access to any of the encryption algorithms. In FY2004 the program was renamed Illness and Injury Surveillance Program with 15 DOE sites participating.
"Beryllium Workers Follow-up Study, Phase II: Screening for Beryllium Sensitivity and Definitive Diagnosis of Chronic Beryllium Disease. Amendment - to add Former Beryllium Workers at all DOE sites where Beryllium was used."
Principal Investigator: Dr. Donna L. Cragle, Oak Ridge Institute for Science and Education
Project started in: 1999
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Full Board
Approving Institution: Oak Ridge Institute for Science and Education
Most recent approval: 11/08/04
IRB approval number: ORAU(99)-87a
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 726
Reporting period for number of human subjects:
Fiscal Year 2005
Type(s) of Human Subjects Involvement:
This project began as a research effort for screening current and former workers at the Y-12 Plant in Oak Ridge, Tennessee. At the beginning of FY1999, the scope was expanded to include former workers at all DOE facilities where beryllium was used.
The Former Beryllium Workers Medical Surveillance Program (BMSP) is composed of five interrelated tasks and includes the identification, notification, scheduling, initial testing, and retesting of former employees of DOE sites who believe they were exposed to beryllium during their employment. Rosters of former employees from DOE sites under the BMSP are obtained and appropriate BMSP notification letters and participation forms are sent to persons on these rosters. Individuals indicating a desire to participate in the BMSP are tested for sensitivity to beryllium and may also be given a chest x-ray if they report respiratory symptoms compatible with chronic beryllium disease (CBD). Persons who show sensitization to beryllium on the first test may be scheduled for a second test to confirm the abnormal finding. Further medical evaluation to determine the presence of CBD may be offered to those who have a normal test, but have suspicious lung pathology on chest x-ray examination or symptoms of CBD that cannot be explained by other disease processes. Retesting is offered once every three to five years to former employees who are found to have normal test results. In addition, retesting is offered every year to former employees who had an abnormal chest x-ray possibly associated with CBD.
Blood is drawn from all study participants for a beryllium lymphocyte proliferation test (Be-LPT). There is little physical risk in drawing the blood. In a few people slight pain and bruising may occur. Rarely is an infection from the needle puncture possible.
Any participant who has one abnormal Be-LPT will be mailed an information package explaining the new Department of Labor (DOL) Energy Employees Occupational Illness Compensation Program Act of 2000 (EEOICPA) and how to apply for benefits through this program. These participants may receive a second Be-LPT through the ORISE program while waiting to be accepted for benefits from DOL. When accepted into the DOL program, all further medical examinations and benefits for the participant should be coordinated and guaranteed by DOL. The DOL program will cover medical monitoring even if the participant chooses not to have a repeat test or if the repeat test is normal. Through this program, participants will have further diagnostic procedures to determine if they have CBD. The majority of participants who have an abnormal Be-LPT apply and are accepted to the DOL program for further follow-up.
Informed consent is obtained for all participants in the Former Beryllium Worker Medical Surveillance Program. Test results are confidential, but not anonymous, and testing staff will only discuss these results with the participant or persons approved by the participants. Participants are free to withdraw at any time without penalty or loss of benefits.
During FY2005, the emphasis of testing was shifted from former DOE workers to former employees of sites that supplied beryllium to DOE operations (vendors).
"Update of a Mortality Study of Titanium Dioxide Workers"
Principal Investigator: Dr. Elizabeth D. Ellis, Oak Ridge Institute for Science and Education
Project started in: 2000
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Full Board
Approving Institution: Oak Ridge Institute for Science and Education
Most recent approval: 07/05/05
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 1158
Reporting period for number of human subjects:
Fiscal Year 2005
Type(s) of Human Subjects Involvement:
The original purpose of the study is to update the cohort mortality study of workers exposed to titanium dioxide. The study is being expanded to include two additional worker cohorts and to include a hazards assessment as part of the analysis. The major components of the new study are computerization of the worker roster and work history; vital status ascertainment using national databases, death certificate retrieval, and cause of death information retrieval; a hazards assessment analysis; comparison of the mortality among the workers to the U.S. general population; and analysis of the risk of mortality related to hazards in the workplace. Since this study will be carried out using existing records, the risks to the study participants originate from loss of privacy of the workers or their survivors. To minimize this risk, access to records is on a need-to-know basis only. All research staff who have access to the records have signed a confidentiality agreement. When not in use, records are kept in locked cabinets. Access to electronic data is password protected.
"Former Pantex Worker Medical Surveillance Program"
Principal Investigator: Dr. Arthur L. Frank, Oak Ridge Institute for Science and Education
Project started in: 2003
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: Oak Ridge Institute for Science and Education
Most recent approval: 02/02/05
IRB approval number: 02510-02p
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 102
Reporting period for number of human subjects:
Fiscal Year 2005
Type(s) of Human Subjects Involvement:
This phase of the project is now conducting medical evaluations as per DOE protocols. It involves standard medical examinations and collection of blood and urine as well as x-rays and pulmonary function testing. Each person fills out detailed questionnaires and a consent form.
"Remote Deception Detection Using Volatile Chemical Emissions Research Project"
Principal Investigator: Dr. Gerhard R. Eisele, Oak Ridge Institute for Science and Education
Project started in: 2004
This project ended in fiscal year 2005.
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Expedited
Approving Institution: Oak Ridge Institute for Science and Education
Most recent approval: 03/02/05
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 52
Reporting period for number of human subjects:
Fiscal Year 2005
Type(s) of Human Subjects Involvement:
The objective of the research was to test the feasibility of developing a system to detect intentional deception by monitoring small changes in natural volatile organic compond (VOC) emissions from the skin surface of individuals. All materials used in the study were innocuous and nontoxic to skin surfaces.
After the strictly voluntary consenting process was completed, study participants first viewed a video of a police file of an actual real-life workplace violence incident. The participant was seated at a table in the testing facility with the forearm placed comfortably in a flexible plastic sampling sleeve. The subject was asked to intentionally lie when answering a question relevant to seeing the video.
During data collection, air samples were drawn off from a person's forearm placed in a sampling sleeve. The air flow was passed through special sampling tubes designed to capture natural VOCs on a sorption medium. The samples were analyzed using gas chromatography/mass spectrometry technology to determine the type and concentration of the VOCs in the air samples coming off the forearm. The resulting data were then analyzed using statistical methods to determine if variations in VOC levels could provide evidence of stress that could be associated with deceptive behavior.
"Survey of Respiratory Symptoms Among Workers in the Forrestal Building"
Principal Investigator: Dr. Elizabeth D. Ellis, Oak Ridge Institute for Science and Education
Project started in: 2004
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Expedited
Approving Institution: Oak Ridge Institute for Science and Education
Most recent approval: 11/20/04
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 42
Reporting period for number of human subjects:
Fiscal Year 2005
Type(s) of Human Subjects Involvement:
The objective of this study is to investigate a health concern among DOE employees in the Forrestal Building in Washington, DC that their recurrent respiratory symptoms are related to their work environment.
A survey will be used to collect information about respiratory symptoms from about 75 employees who work in or near the area in which the concerned employees work. A letter and survey form will be sent to each employee. After reading the letter, the employee will decide whether to complete and return the survey to DOE EH-6 staff. Pseudo-identifiers will be assigned to each survey form before it is sent to ORISE for computerization.
"Message Testing for Prevention of Carbon Monoxide Poisoning Among Immigrants"
Principal Investigator: Dr. Richard R. Tardif, Oak Ridge Institute for Science and Education
Project started in: 2005
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Expedited
Approving Institution: Oak Ridge Institute for Science and Education
Most recent approval: 10/08/04
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 136
Reporting period for number of human subjects:
Fiscal Year 2005
Type(s) of Human Subjects Involvement:
An ice storm struck Charlotte, NC resulting in an extended power outage. A total of 124 cases of carbon monoxide poisoning occurred, many of these among members of the Hispanic community where a number of people, especially newer immigrants, used charcoal grills inside their homes for heat. The Asthma Prevention and Respiratory Health Branch of the Centers for Disease Control and Prevention (CDC) provides technical assistance to the states in the prevention of carbon monoxide poisoning. As part of their assistance to North Carolina, CDC has prepared Public Service Announcements in Spanish warning of the dangers of carbon monoxide poisoning from improperly vented heating sources. CDC wants to test these announcements with members of the Hispanic community in Charlotte. The primary objectives of this project are to: test comprehension of the Public Service Announcements; identify barriers to safe heating of homes during power outages for the target audience; assess the knowledge of members of Charlotte's Hispanic community regarding carbon monoxide; identify credible spokespersons for public health messages for the target audience; and identify sources of additional information that are likely to be used by the target audience.
"DOE National Supplemental Screening Program"
Principal Investigator: Dr. Joseph Furman, Oak Ridge Institute for Science and Education
Project started in: 2005
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: Oak Ridge Institute for Science and Education
Most recent approval: 06/10/05
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 26
Reporting period for number of human subjects:
Fiscal Year 2005
Type(s) of Human Subjects Involvement:
Identify groups of former workers at risk for occupational disease, notify these individuals, and offer them medical screening that can lead to medical tratment. The objective is to provide high quality medical evaluations to former DOE workers so that occupationally related health effects may be identified. Workers who are found to have health conditions requiring further evaluation and treatment will be referred to their private medical physicians and to others in the medical community for follow-up.
"Formative Research: Testing of Pandemic Influenza Messages with the Public and Health Care Providers"
Principal Investigator: Dr. Richard R. Tardif, Oak Ridge Institute for Science and Education
Project started in: 2005
This project ended in fiscal year 2005.
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Expedited
Approving Institution: Oak Ridge Institute for Science and Education
Most recent approval: 07/18/05
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 9
Reporting period for number of human subjects:
Fiscal Year 2005
Type(s) of Human Subjects Involvement:
Pandemic influenza has occurred at least 30 times in recorded history and three times in the last century. It is characterized by the occurrence of a strain of influenza to which few people have immunity. The disease then spreads rapidly to most if not all areas of the world. While pandemic influenza is likely to occur again, there is substantial uncertainty about predicting the specifics of a pandemic. Given the likely occurrence, possible consequences, and uncertainty of pandemic influenza, the United States and national and international agencies deem planning and preparedness to be prudent. As part of its efforts, the U.S. Department of Health and Human Services (HHS) is preparing communication materials to inform stakeholders about pandemic influenza and issues associated with it. HHS wants to test the draft communication materials with their intended target audiences to help ensure that the materials are comprehensible and address stakeholder questions.
"Amendment: Use of NDA Prussian Blue for Internal Decontamination of Radiocesium (NDA)"
Principal Investigator: Dr. Patrick C. Lowry, Oak Ridge Institute for Science and Education
Project started in: 2005
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Expedited
Approving Institution: Oak Ridge Institute for Science and Education
Most recent approval: 11/09/04
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Other: 06/01/04 to 05/31/05
Explanation:
U.S. FDA project year
Type(s) of Human Subjects Involvement:
Prussian Blue (ferric ferrocynate) is well studied as an ion-exchange resin which is quite efficacious in the decorporation therapy required for patients with high body burdens of radiocesium, radiothallium, or stable thallium. Anyone in the DOE system or with internal contamination with radiocesium, radiothallium, or stable thallium is eligible for treatment with Prussian Blue. Those with internal contamination with radiocesium, radiothallium, or stable thallium elsewhere in the U.S. outside the DOE system are also eligible with DOE approval for treatment if Prussian Blue is not available. Prussian Blue is manufactured under its New Drug Application (NDA) by Heyl Gmb of Germany is not considered investigational. Physicians can write prescriptions for Prussian Blue and pharmacies can carry Prussian Blue. Prussian Blue, under the NDA, should be widely available, but there are many locales in the U.S. where it is not immediately available.
There has been no use of Prussian Blue for internal contamination with either radiocesium, radiothalliumin, or stable thallium in the most recent reporting period (6/1/04 to 5/31/05).
ORAU-81, Use of Prussian Blue for Internal Decontamination of Radiocesium and Thallium, has been granted by the Food and Drug Administration's (FDA) Investigation New Drug (IND) 51,700. Despite the approval of an NDA for Prussian Blue to Heyl GmBH, the IND for Prussian Blue is planned at this time to continue but the project remains an inactive (see Project 91-81). The project will continue in the DOE community using NDA drug (see admendment July 20, 2005). A supply of Prussian Blue, obtained from the German company Heyl GmBH, is currently distributed to six co-investigators in the DOE complex. This product, although manufactured by Heyl under the IND, has been determined to meet NDA standards and the FDA has authorized ORISE in writing to use the product of Batch # 014082 as NDA quality product. Therefore all Prussian Blue now with co-investigators is from this batch and so can be treated as NDA product.
Prussian Blue is to be used in the U.S. DOE complex as a decorporation agent for patients internally contaminated with medically significant amounts of radiocesium and radiothallium. In this document, the name Insoluble Prussian Blue (PB) without further specification indicates the following compound: Ferric(III) hexacyanoferrate(II) "insoluble PB," Fe4 [Fe (CN)6]3, molecular weight: 859.3, Color Index No. 77.510, and CAS Registry No. 14038-43-8. Under the NDA (#58060-00201) Insoluble Prussian Blue is also known as Radioguardase. Insoluble Prussian Blue has been recommended for years as the drug of choice by national and international radiation protection societies for use in treating internal contamination with radiocesium. It was effectively used in the treatment of patients contaminated with Cs-137 in the 1987 Goiania, Brazil accident under temporary clearance by FDA for "compassionate use" by the ORAU's REAC/TS program.
Prussian Blue is distributed by the Oak Ridge Institute for Science and Education (ORISE) to DOE co-investigators for DOE facilities throughout the country. Up until July 20, 2005, prussian blue was distributed under the IND. After the amendment for Project 81 of July 20, 2005, it is not available as IND but is as NDA product at DOE facilities participating in the ongoing safety and efficacy study (ORAU 91-81). As an NDA, Prussian Blue is technically available throughout the country from pharmacies with a physician's prescription. However, it is not generally available as yet and ORISE/REAC/TS with DOE approval can also provide limited amounts of Prussian Blue to non-DOE personnel.
ORISE is managed by Oak Ridge Associated Universities (ORAU), under contract with the U.S. Department of Energy (DOE). Insoluble PB, ferric hexacyanoferrate, Fe4[Fe(CN)6]3 is a drug that enhances excretion of isotopes of cesium and thallium from the body by means of ion exchange. It has had a long and successful history in the treatment of internal contamination with radiocesium. In the normal course of DOE operations, internal contamination with radioactive cesium is thought to be more likely than with radiothallium.
Of the various radioisotopes of cesium, Cs-137 is the most important. Cs-137 is a common fission by-product material, a frequent active component of sealed sources, and an important radionuclide in radiation oncology. The use of Cs-137 falls under the jurisdiction of the Nuclear Regulatory Commission (NRC). It is a ubiquitous radionuclide found throughout the DOE system and in hospitals performing either gynecological brachytherapy or interstitial therapy for solid tumors. Until the Goiania incident in Brazil, there were very few cases of radiocesium contamination requiring decorporation therapy. However, there is an increasing potential for such contamination to occur and a need for specific therapy. Additionally, given its widespread availability and its chemical characteristics, it is considered as a prime candidate for use in a terrorist event, such as a dirty bomb. The recent increase in workers performing remediation work at hazardous waste sites also requires that clinicians have Insoluble Prussian Blue available and understand the nature of its pharmacodynamics.
See amendment July 20, 2005 for more details.
"Amendment: Use of Ca-DTPA and Zn-DTPA (NDA product) for Chelation Therapy of Heavy Metals"
Principal Investigator: Dr. Patrick C. Lowry, Oak Ridge Institute for Science and Education
Project started in: 2005
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Expedited
Approving Institution: Oak Ridge Institute for Science and Education
Most recent approval: 06/20/05
Explanation of IRB approval:
Approval by board in July 2005.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Other: 06/01/04 to 05/31/05
Explanation:
U.S. FDA project year.
Type(s) of Human Subjects Involvement:
Investigational new drug (IND) 4041, trisodium calcium diethylenetriaminepentaacetate (Ca-DTPA), and IND 14603, trisodium zinc diethylenetriaminepentaacetate (Zn-DTPA) formerly used in this study has been replaced by New Drug Application (NDA) product and as a result are no longer considered investigational. Because the Food and Drug Administration (FDA) awarded NDA approval of Ca- and Zn-DTPA based predominently on the animal studies and the "animal rule," DOE and project co-investigators desired to continue safety and efficacy studies on these chelators and to continue the study at the Oak Ridge Associated Universities under contract with the U.S. Department of Energy. New supplies of NDA product for both DTPAs have been imported from Hamelm of Germany and distributed to co-investigators in July 2005. All IND product except that at the Strategic National Stockpile (SNS), Centers for Disease Control and REAC/TS was recalled and has been stored at ORISE/ORAU under management of REAC/TS. Ca- and Zn-DTPA have recently (2004 reporting period) been classified by the U.S. FDA as New Drug Application and product manafactured under the NDA are no longer considered investigational. Both Ca- and Zn-DTPA manufactured under the NDA are approved by both the U.S. Food and Drug Administration and DOE/Environment Safety and Health and meet the chemical specifications of the U.S. Pharmacopeia (USP 23) and that of the European Union (Pharm. Eur.) This project will deal only with NDA product, now available by prescription by physicians throughout the U.S. but limited by availability. This study focuses mainly on NDA product use at DOE facilities and with existing co-investigators.
DTPA belongs to the group of synthetic polyamino polycarboxylic acids which form stable complexes (metal chelates) with a large number of metal ions, especially the transuranic elements. The drug effectively exchanges calcium or zinc for another metal of greater binding power and carries it to the kidneys where it is then excreted. Historically, in the DOE laboratory complex, DTPA has been quite successful in promoting urinary excretion of the actinide elements in accident situations where inhalation or systemic uptake through wounds was involved.
Ca-DTPA is approximately 10 times more effective than Zn-DTPA for the initial chelation of transuranic elements. Therefore, Ca-DTPA should be used whenever larger body burdens of transuranics are involved. Ca-DTPA is the drug of choice for initial patient management of internal contamination with transuranic elements unless contraindicated. After approximately 24 hours, however, Zn-DTPA is, for all practical purposes, as effective as Ca-DTPA. This comparable efficacy, coupled with its lesser toxicity, makes Zn-DTPA the preferred agent for protracted therapy. The effectiveness of chelation therapy is highly dependent not only on the metal itself, but also on the chemical and physical characteristics of the compound at the time of DTPA administration. Because the efficiency of chelation decreases with time, DTPA ideally should be given within six hours of exposure.
Accidents involving internal contamination with the actinide elements (Pu, Am, and Cm) occur in the DOE complex and both Ca-DTPA and Zn-DTPA have proven effectiveness in the medical management of these cases. Anyone in the DOE system or elsewhere with internal exposure to actinides (Pu, Am, Cm, etc.) is eligible for treatment with Ca-DTPA and Zn-DTPA. Most cases of internal contamination involve inhalation of the material, but uptake through wounds has occured in some reporting periods.
There have been no cases of administration of either Ca- or Zn-DTPA since distribution of the NDA product.