- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00005537
Genetics of Airway Responsiveness and Lung Function
Study Overview
Status
Detailed Description
DESIGN NARRATIVE:
Airway responsiveness and lung function, endpoints with a strong genetic basis, are central to the obstructive airway diseases (asthma and COPD). In contrast, the dissection of the underlying genes requires unique sample resources, accurate and comprehensive phenotyping, and an efficient study design. To address to this three-pronged challenge, a genomic screen brought together a large, homogenous, mostly untreated sample from Anhui, China, a wealth of expertise in asthma phenotypes, and a potent study design based on extreme discordant sib pairs.
Since this approach utilized an extant asthmatic family population, no support for data collection was required. The primary focus of the study was two intermediate phenotypes related to asthma and COPD: airway responsiveness (characterized by increased responsiveness to histamine methacholine or other nonspecific agonists and measured by the slope of the dose response relationship) and forced expiratory volume in 1 second (FEV1). Since both traits are continuous, the appropriate study design considered only siblings with extremely discordant phenotypes. For many studies, this strategy was not feasible due to the thousands of families that must be phenotyped to identify a sample of such siblings. The plan was to utilize the organization of a well-established network in China to collect 150 extreme discordant sib pairs of each intermediate phenotype. For airway responsiveness, the estimated power from this sample, equivalent to roughly 600 concordant sib pairs, was intended to surpass the power of all existing studies, including the U.S. Collaborative Study on the Genetics of Asthma. Further, with similar power, this was the first study to test for linkage to FEV1. Moreover, to further augment power, potential phenotypic heterogeneity was reduced by stratifying the analyses by total and specific serum IgE levels, skin test reactivity, peripheral blood eosinophilia, respiratory symptoms, age, gender, bronchodilator response, and cigarette smoking.
The study completion date listed in this record was obtained from the "End Date" entered in the Protocol Registration and Results System (PRS) record.
Study Type
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Study Plan
How is the study designed?
Collaborators and Investigators
Investigators
- Xiping Xu, Brigham and Women's Hospital
Publications and helpful links
General Publications
- Hu FB, Wang B, Chen C, Jin Y, Yang J, Stampfer MJ, Xu X. Body mass index and cardiovascular risk factors in a rural Chinese population. Am J Epidemiol. 2000 Jan 1;151(1):88-97. doi: 10.1093/oxfordjournals.aje.a010127.
- Xu X, Yang J, Chen C, Wang B, Jin Y, Fang Z, Wang X, Weiss ST. Familial aggregation of pulmonary function in a rural Chinese community. Am J Respir Crit Care Med. 1999 Dec;160(6):1928-33. doi: 10.1164/ajrccm.160.6.9902013. Erratum In: Am J Respir Crit Care Med. 2002 Sep 1;166(5):774.
- Wang X, Wang B, Chen C, Yang J, Fang Z, Zuckerman B, Xu X. Familial aggregation of blood pressure in a rural Chinese community. Am J Epidemiol. 1999 Mar 1;149(5):412-20. doi: 10.1093/oxfordjournals.aje.a009828.
- Xu X, Niu T, Chen C, Wang B, Jin Y, Yang J, Weiss ST. Association of airway responsiveness with asthma and persistent wheeze in a Chinese population. Chest. 2001 Mar;119(3):691-700. doi: 10.1378/chest.119.3.691. Erratum In: Chest 2002 Jun;121(6):2085.
- Betensky RA, Hudson JI, Jones CA, Hu F, Wang B, Chen C, Xu X. A computationally simple test of homogeneity of odds ratios for twin data. Genet Epidemiol. 2001 Feb;20(2):228-38. doi: 10.1002/1098-2272(200102)20:23.0.CO;2-4.
- Niu T, Rogus JJ, Chen C, Wang B, Yang J, Fang Z, Weiss ST, Xu X. Familial aggregation of bronchodilator response: a community-based study. Am J Respir Crit Care Med. 2000 Nov;162(5):1833-7. doi: 10.1164/ajrccm.162.5.9908127. Erratum In: Am J Respir Crit Care Med. 2002 Sep 1;166(5):774.
- Xu X, Fang Z, Wang B, Chen C, Guang W, Jin Y, Yang J, Lewitzky S, Aelony A, Parker A, Meyer J, Weiss ST, Xu X. A genomewide search for quantitative-trait loci underlying asthma. Am J Hum Genet. 2001 Dec;69(6):1271-7. doi: 10.1086/324650. Epub 2001 Oct 22. Erratum In: Am J Hum Genet 2002 Jul;71(1):215.
- Venners SA, Wang X, Chen C, Wang B, Ni J, Jin Y, Yang J, Fang Z, Weiss ST, Xu X. Exposure-response relationship between paternal smoking and children's pulmonary function. Am J Respir Crit Care Med. 2001 Sep 15;164(6):973-6. doi: 10.1164/ajrccm.164.6.2009063. Erratum In: Am J Respir Crit Care Med. 2002 Sep 1;166(5):775.
- Wang Z, Chen C, Niu T, Wu D, Yang J, Wang B, Fang Z, Yandava CN, Drazen JM, Weiss ST, Xu X. Association of asthma with beta(2)-adrenergic receptor gene polymorphism and cigarette smoking. Am J Respir Crit Care Med. 2001 May;163(6):1404-9. doi: 10.1164/ajrccm.163.6.2001101. Erratum In: Am J Respir Crit Care Med. 2002 Sep 1;166(5):775.
Study record dates
Study Major Dates
Study Start
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 5071
- R01HL056371 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Lung Diseases, Obstructive
-
Assistance Publique - Hôpitaux de ParisCompletedChronic Obstructive Lung Disease (COLD)France
-
Centre Hospitalier Intercommunal CreteilRecruitingChronic Obstructive Pulmonary Disease | Chronic Obstructive Lung DiseaseFrance
-
Heidelberg UniversityTerminatedObstructive Lung DiseasesAustralia, Germany
-
Imperial College LondonAstraZenecaCompleted
-
Columbia UniversityAstraZenecaTerminated
-
PharmaLundensis ABCompletedChronic Obstructive Lung DiseaseSweden
-
RWTH Aachen UniversityCompletedObstructive Lung DiseasesGermany
-
Philip DiazCompletedChronic Obstructive Lung DiseaseUnited States
-
University Hospital, Gentofte, CopenhagenCompletedChronic Obstructive Lung DiseaseDenmark
-
Schön Klinik Berchtesgadener LandCompletedChronic Obstructive Lung Disease