Identifying Shared Genetic Susceptibility Regions in Chronic Beryllium Disease and Sarcoidosis

Sarcoidosis Clinical Trial

Official title:

Shared Genetic Susceptibility in CBD and Sarcoidosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00560989
• Other study ID #: 1382
• Secondary ID: R21HL081766R21HL
• Status: Completed
• Phase: N/A
• First received: November 16, 2007
• Last updated: September 24, 2014
• Start date: March 2007
• Est. completion date: March 2007

Study information

• Verified date: September 2014
• Source: National Jewish Health
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Observational

Clinical Trial Summary

Granulomatous lung diseases are diseases in which inflamed clusters of white cells, known as granulomas, form in lung tissue. Chronic beryllium disease (CBD) and sarcoidosis are two granulomatous diseases that share similar clinical symptoms, physiological changes in the lungs, and immune responses to the disease. Genetic variations may make some people more susceptible to developing CBD or sarcoidosis. This study will identify common genetic regions associated with increased risk of developing the granulomatous diseases CBD and sarcoidosis.

Description:

CBD and sarcoidosis are granulomatous lung diseases that are caused by an abnormal immune response. While CBD is known to develop from exposure to the industrial product beryllium, the cause of sarcoidosis remains undetermined. CBD occurs in 2 to 16% of people exposed to beryllium and varies in severity of symptoms. People with sarcoidosis often show very minor symptoms. However, certain variables have been associated with the more severe forms of disease. These variables include black race, onset over the age of 40, involvement of more than three affected organs, and presence of more serious lung disease. When serious symptoms of sarcoidosis occur, clinical and pathological appearances of CBD and sarcoidosis are often hard to distinguish. Symptoms common to both diseases include fever, chest pain, weight loss, night sweats, fatigue, and presence of granulomas on the lungs. The fact that the severity of both diseases varies greatly among those affected points to possible genetic involvement. The genetic basis being analyzed in this study begins with the similar immune responses in the development of both diseases, specifically involving human leukocyte antigen (HLA) gene products. The purpose of this study is to identify common genetic regions associated with increased risk of developing the granulomatous diseases CBD and sarcoidosis.

This study will utilize a novel technique, known as a genome-wide scan. The study will examine previously collected DNA samples from participants in a previous NIH study, A Case Control Etiologic Study of Sarcoidosis (ACCESS), and from participants with CBD recruited at the National Jewish Medical and Research Center. Using the genome scans, researchers will compare genetic regions of people with CBD versus people without CBD who have been exposed to beryllium. The same approach will be used to define genetic regions associated with sarcoidosis. Genome control methods will be used to account for population stratification in both the CBD and sarcoidosis populations. Researchers will compare data between diseased and healthy control groups and between CBD and sarcoidosis groups to identify shared genetic regions relevant to disease development. A second genome scan involving two larger populations of CBD and sarcoidosis cases and controls will be conducted to confirm the association of these regions with both diseases.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 400
• Est. completion date: March 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Has previously participated in beryllium studies conducted by Dr. Lisa Maier

• Agrees to allow the use of personal medical records and genetic material for future research by study officials

Exclusion Criteria:

• Will not consent for use of DNA for research purposes or for storage

• Any beryllium or sarcoidosis DNA specimens without an optical density of 260/280 nm, ratio between 1.8 and 2.0, or with an insufficient quantity of DNA for analysis purposes

Study Design

Observational Model: Case Control, Time Perspective: Retrospective

Related Conditions & MeSH terms

• Berylliosis
• Disease Susceptibility
• Genetic Predisposition to Disease
• Sarcoidosis

Locations

Country	Name	City	State
United States	National Jewish Medical and Research Center	Denver	Colorado

Sponsors (2)

Lead Sponsor	Collaborator
National Jewish Health	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Shared genetic regions associated with the risk of the granulomatous diseases CBD and sarcoidosis		Measured at completion of genetic analysis
Secondary	Genetic/chromosomal regions associated with CBD and sarcoidosis		Measured at completion of genetic analysis