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Exposure in Epigenetic Regulation of Immune Response in Chronic Beryllium Disease (CBD)

Study Purpose

This study will provide important results for each aim, while also providing an integrative transcriptional and epigenomic profile of CBD. In Aim 1 the Investigator will define genome-wide epigenetic alterations of CBD, by determining genes that are DM in pivotal immune cells, in the target organ (CD4+ BAL cells) in CBD compared to BeS and healthy controls. In addition, the Investigator will determine the impact of Be exposure on the methylation profile of CBD and BeS cells compared to each other and normal controls. This information will be used to define DM regions, genes and their networks. Using the cases and controls from Aim 1, we will evaluate the gene-expression from these same subjects in Aim 2 to define functional epigenetic loci based on DE in CD4+ BAL cells with and without Be exposure. The Investigator will also integrate ENCODE/RE methylation, histone modification, and chromatin accessibility data as well as our genome-wide association study (GWAS) data to prioritize epigenetic marks and networks for confirmation and validation in Aim 3. In Aim 3, the Investigator will test the generalizability of their findings, explore the potential of methylation marks as biomarkers of disease in PBMCs and determine if change in methylation of these targets with AZA or folic acid affects key immune and regulatory pathways in a second set of CBD and BeS subjects. Throughout the Aims, the Investigator will use both fresh CD4+ T cells to directly assess disease relevance and Be-stimulated cultured CD4+ T cells (compared to unstimulated cultured T cells) to assess the impact of environmental exposure .

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	Yes
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Observational
Eligible Ages	18 Years - 80 Years
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

Chronic Beryllium Disease (CBD): 1. History of Beryllium exposure. 2. Positive blood and/or bronchoalveolar lavage (BAL) Beryllium Lymphocyte Proliferation Tests (BeLPT) 3. Biopsy-proven pathologic changes consistent with CBD, specifically non-caseating granulomas and/or mononuclear cell interstitial infiltrates. Beryllium Sensitization: 1. History of Beryllium exposure. 2. Two or more positive blood beryllium lymphocyte proliferation tests (BeLPT) or positive bronchoalveolar lavage (BAL) BeLPT. 3. Normal lung tissue (no histology suggestive of CBD). Normal Controls: 1. No history of beryllium exposure. 2. Former smokers or never smokers

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Exclusion Criteria:
Chronic Beryllium Disease: 1.

Immunosuppressive therapy within the last three months. 2. Current cigarette smoking or smoking within six months prior to the study. 3. Positive lung washing or biopsy cultures for fungi, mycobacteria or other respiratory pathogen consistent with an acute or chronic infection. 4. Weight less than 110 lbs. (for venipuncture) 5. Pregnancy. 6. Severe room air hypoxemia and or hypercapnia (precluding BAL), e.g., resting PaO2 < 45, PaCO2 > 45 mm Hg; (Denver altitude 5,280 feet) 7. Presence of another disease that may be expected to significantly affect patient mortality and or the immune response (e.g., HIV, HCV, cancer, uncorrected bleeding diathesis, acute hypercapnia with a resting PaCO2 above 45 mm Hg; serious cardiac arrhythmia, recent myocardial infarction within 6 weeks) 8. Patient inability to participate in the study, such as inability to undergo venipuncture and BAL procedures that form part of the inclusion/exclusion criteria or part of the outcome measure. Beryllium Sensitization: 1. Known underlying systemic or lung disease; 2. Current cigarette smoking or smoking within six months prior to the study. 3. Positive lung pathology consistent with CBD. 4. Pregnancy. 5. Weight less than 110 lbs. (for venipuncture) 6. Presence of another disease that may be expected to significantly affect patient mortality and or the immune response (e.g., HIV, HCV, cancer, uncorrected bleeding diathesis, serious cardiac arrhythmia; recent myocardial infarction within 6 weeks) 7. Patient inability to participate in the study, such as inability to undergo venipuncture and BAL procedures that form part of the inclusion/exclusion criteria or part of the outcome measure. Normal Controls: 1. History of beryllium exposure. 2. Known underlying systemic or lung disease; 3. Immunosuppressive therapy or other medication for as systemic disease process in the last 3 months; 4. Current smokers or smoking within 6 months of study. 5. Pregnancy. 6. Weight less than 110 lbs. (for venipuncture) 7. Inability to undergo BAL or venipuncture procedures -

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT02604693
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	National Jewish Health
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Lisa Maier, MD
Principal Investigator Affiliation	National Jewish Health
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Chronic Beryllium Disease

Arms & Interventions

Arms

: Chronic Beryllium Disease

Those that have been diagnosed with the disease. No interventions will be administered.

: Beryllium Sensitization

Those that have been diagnosed with beryllium sensitization and do not have chronic beryllium disease. No interventions will be administered.

: normal controls

Those that do not have chronic beryllium disease or beryllium sensitization. No interventions will be administered

Interventions

Other: - Nothing

No interventions will be administered.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

National Jewish Health, Denver, Colorado

Status

Recruiting

Address

National Jewish Health

Denver, Colorado, 80206

Site Contact

Peggy M Mroz, MSPH

mrozp@njhealth.org

303-398-1730