National Jewish Medical and Research Center

Funding for Human Subjects Research:

Federal: National Institutes of Health (NIH)

$15,000.00 (Est.) for: Other time period
Reporting period for National Jewish fiscal year 2005: 7/1/04 to 6/30/05.
Percent of funding associated with the use of human subjects: 1-20

Information on Use of Human Subjects:

This project does not involve the use of multiple protocols/subprojects.

Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: National Jewish Medical and Research Center
Most recent approval: 08/31/05
Explanation of IRB approval:
N/A

Additional IRB approvals from other institutions:
Type of Review: Full Board
Approving Institution: Central Beryllium Institutional Review Board
Most recent approval: 06/16/05

Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 184
Reporting period for number of human subjects: Other: 07/01/04 to 06/30/05
Explanation:

Reporting period for National Jewish fiscal year 2004: 7/1/04 to 6/30/05.

Type(s) of Human Subjects Involvement:

Collection of personally identifiable bodily materials (blood or blood products, urine, cells, tissue, teeth, organs, excreta, etc):

• Using bodily materials collected specifically for this project.

Use of personally identifiable data from questionnaires, surveys, or epidemiological studies:

• Using existing data that were collected for other purposes or projects.

(a. Objectives, b. Methodology, c. Ionizing Radiation, Radioactive Substances, or Chemical Substances to which human subjects are exposed, d. Involvement of Human Subjects [d.1. procedures used, d.2. risks if any])

Objective:
We propose to better define exposure specific variables alone and in combination with genetic variation in chronic beryllium disease (CBD) and beryllium sensitization (BeS) risk in a cohort of workers exposed to beryllium. We will do this by (1) defining exposure variables associated with BeS and CBD and (2)assessing the relative contribution of the genetic polymorphisms and exposure on disease development.

While study participants receive no direct benefit, a better understanding of disease in regards to beryllium exposure and genetics may lead to many benefits including: (1) Knowledge will increase our understanding of the disease; (2) Identifying a protective level of beryllium exposure could lead to preventing disease among future workers; (3) Understanding the genetic mechanisms of the disease may promote the development of more effective diagnostic tools and treatment; and (4) Knowing why some people with BeS and CBD get sicker than others can give us insight in providing treatment.

Methodology:
A case control study will examine exposure and genetic factors contributing to BeS and CBD. Over the study period, we will enroll up to 140 BeS and CBD cases and two beryllium-exposed, non-diseased controls per case enrolled. We will match cases and controls by self-reported race and ethnicity and decade of hire.

Blood will be drawn for extraction of DNA genetic typing. Participants will be asked to complete a self-administered questionnaire consisting of demographic and smoking history questions. An interviewer-administered questionnaire will be completed by each study subject to obtain detailed work histories, including job titles, percent time worked with beryllium, work location (building), work processes, use of personal protective equipment, and form of beryllium used in the workplace (metal vs. alloy vs. ceramic). Interactions between exposure variables and Human Leukocyte Antigen-Class II (HLA-Class II) variants, focusing on Glu69 and the TNF-a promoter variants will be determined.

Involvement of human subjects:
(1) Procedures are listed above.
(2) Blood Draw: Subjects may feel pain when the needle goes into the vein. A bruise may form at the site. There is a small risk of fainting. Questionnaires: The questionnaires do not involve any physical risk. Review of Work Histories/Clinical Data/Medical Records: There is no physical risk involved in reviewing participant records. Non-Physical Risks: We recognize current and former workers as a vulnerable population for non-physical risks and include coercive pressure, breach of privacy and confidentiality, insurability and employability.
(3) Consent Process: Participation must be voluntary, therefore, informed consent will be obtained for all procedures from all subjects prior to entry into the study protocol. Informed consent will take place in a private setting. Potential subjects will be allowed as much time as they require to make a thoughtful and reasoned decision. If the person desires, he/she may take the informed consent information with them to discuss further with family and other advisors.

Privacy/Confidentiality Protections:
We have obtained a Certificate of Confidentiality, issued by the National Institutes of Health (NIH) under the Public Health Service Act (41 U.S.C. 241(d)), which protects the principle investigators of this study as well as National Jewish from having to release personal identifying information about study participants. Study participants' personal identifying information will be protected from civil, criminal, administrative, and legislative proceedings at the federal, state, and local levels. Our Certificate will remain in effect until the study is completed. Protection of study participants' personal identifying information is permanent.

To protect personal privacy and maintain confidentiality, subjects will be assigned unique four-digit study identification numbers, which bear no identifying information. Personal identifying information will be removed from samples and questionnaires. Subject names and other identifying information will be separated from the DNA samples before they are sent for genetic research studies.