Genetic Mechanisms of Chronic Obstructive Pulmonary Disease (COPD)

Tracking Information
First Submitted Date	July 3, 2001
First Posted Date	July 5, 2001
Last Update Posted Date	January 21, 2009
Study Start Date	October 1998
Primary Completion Date	Not Provided
Current Primary Outcome Measures	Not Provided
Original Primary Outcome Measures	Not Provided
Change History	Complete list of historical versions of study NCT00018408 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures	Not Provided
Original Secondary Outcome Measures	Not Provided
Current Other Outcome Measures	Not Provided
Original Other Outcome Measures	Not Provided
Descriptive Information
Brief Title	Genetic Mechanisms of Chronic Obstructive Pulmonary Disease (COPD)
Official Title	Genetic Mechanisms of Chronic Obstructive Pulmonary Disease
Brief Summary	The purpose of this study is to determine whether genetic factors contribute to an individuals risk of developing obstructive lung disease from smoking cigarettes.
Detailed Description	Chronic obstructive pulmonary disease (COPD) is among the most important chronic diseases of adults. It is the fourth leading cause of death in the U.S. and affects more than 10% of the U.S. population over age 55. COPD accounts for more than 25,000 discharges annually from VA medical centers. Cigarette smoking is the most important known modifiable cause of COPD, yet only 15-20% of cigarette smokers develop clinically significant COPD. We therefore hypothesize that genetic mechanisms determine susceptibility to the development of COPD. The only genetic abnormality known to cause COPD is deficiency of the serine protease inhibitor 1-protease inhibitor, which causes premature development of emphysema, although it is implicated in fewer than 2% of COPD cases. Several other genetic variants have been proposed as candidate causes of COPD; however, these have been identified on the basis of association studies in unrelated subjects, which have considerable risk of ascertainment bias. In the present study, a sub-pair linkage approach will be utilized in COPD patients and their smoking siblings to identify genes which determine the risk of developing COPD. The following are the short-term objectives of this study: Recruit a cohort of 400 probands with smoking-related COPD and their smoking siblings, whether or not affected by COPD. Affected subjects will be extensively characterized as to specific COPD phenotype, using spirometry, computed tomography, and questionnaire data.; Test the association of known genetic variants in candidate genes to the presence of COPD.; For proposed candidate genes without known candidate polymorphisms, use sib-pair linkage analysis to test polymorphic marker loci in close proximity to the candidate gene for evidence of linkage to COPD.; Test for heterogeneity of linkage among different COPD phenotypes: predominant emphysema versus predominant airway disease. The long-term objective of this research is the identification of specific genetic variants which confer risk for the development of COPD in smokers. This will be achieved by means of fine mapping of the loci identified in objectives 3-4 above, or in a subsequent genome scan involving the 400 sibling pairs; identification of novel genetic variants at these loci; and assessment of the functional significance of these variants and their relation to COPD in an independent sample of subjects. Recruitment of subjects for this project began in April, 1999. At this time, a total of 22 subjects (11 COPD patients and 11 first-degree relatives) have been recruited and tested. No adverse events have occurred. A computerized methodology for quantitation of emphysema from CT scans has been developed and has demonstrated adequate DNA extraction from our blood samples. Genotyping has been deferred pending the recruitment of 50 subjects.
Study Type	Observational
Study Design	Time Perspective: Retrospective
Target Follow-Up Duration	Not Provided
Biospecimen	Not Provided
Sampling Method	Not Provided
Study Population	Not Provided
Condition	Chronic Obstructive Lung Disease
Intervention	Not Provided
Study Groups/Cohorts	Not Provided
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status	Completed
Enrollment	Not Provided
Original Enrollment	Not Provided
Study Completion Date	September 2001
Primary Completion Date	Not Provided
Eligibility Criteria	Age greater than or equal to 40 years; Cigarette smoking greater than or equal to 30 pack years; Obstructive Spirometry; First degree relative with smoking history willing to participate
Sex/Gender	Sexes Eligible for Study: All
Ages	40 Years and older (Adult, Senior)
Accepts Healthy Volunteers	Yes
Contacts	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries	United States
Removed Location Countries
Administrative Information
NCT Number	NCT00018408
Other Study ID Numbers	CADE-ARCD1
Has Data Monitoring Committee	Not Provided
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Not Provided
Study Sponsor	VA Office of Research and Development
Collaborators	Not Provided
Investigators	Not Provided
PRS Account	VA Office of Research and Development
Verification Date	December 2004