Molecular Phenotypes for Cystic Fibrosis Lung Disease

Cystic Fibrosis Clinical Trial

Official title:

Molecular Phenotypes for Cystic Fibrosis Lung Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01116414
• Other study ID #: 08-1509
• Secondary ID: 5R01HL095396697
• Status: Completed
• Start date: July 2009
• Est. completion date: October 25, 2023

Study information

• Verified date: October 2023
• Source: University of North Carolina, Chapel Hill
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to develop an integrated view of molecular mechanisms underlying CF lung disease severity.

Description:

BACKGROUND: Cystic fibrosis (CF) is a recessive genetic disorder caused by mutations in CF transmembrane conductance regulator (CFTR) gene. CF has multi-organ involvement, but respiratory disease is the major cause of morbidity and mortality. The median age of survival in CF is only 37 years, but there is a broad range of disease severity in the lung, even among patients with identical CFTR genotypes, including deltaF508 homozygotes. DESIGN NARRATIVE: This project holds great promise for defining a robust molecular phenotype for CF lung disease, which relates to prognosis, and new targets for therapy. By using a large and well-defined population of deltaF508 homozygotes who also have whole genome single nucleotide polymorphism (SNP) data, and by studying gene expression across the whole transcriptome in a large number of samples of two relevant tissues (respiratory epithelium and transformed lymphocytes), we will be uniquely positioned to develop an integrated view of molecular mechanisms underlying CF lung disease severity.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 152
• Est. completion date: October 25, 2023
• Est. primary completion date: December 13, 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years and older

Eligibility

Inclusion Criteria:

• Diagnosed with CF
• Participation in Genetic Modifiers of CF Lung Disease study (NCT00037765)

Exclusion Criteria:

• History of lung transplant
• Fully anticoagulated or clotting abnormalities
• Large nosebleed in the last 2 months
• Acutely ill

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis
• Lung Diseases
• Pulmonary Fibrosis

Locations

Country	Name	City	State
United States	Johns Hopkins University	Baltimore	Maryland
United States	The University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Case Western Reserve University	Cleveland	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (4)

Dang H, Polineni D, Pace RG, Stonebraker JR, Corvol H, Cutting GR, Drumm ML, Strug LJ, O'Neal WK, Knowles MR. Mining GWAS and eQTL data for CF lung disease modifiers by gene expression imputation. PLoS One. 2020 Nov 30;15(11):e0239189. doi: 10.1371/journal.pone.0239189. eCollection 2020. — View Citation

Drumm ML, Konstan MW, Schluchter MD, Handler A, Pace R, Zou F, Zariwala M, Fargo D, Xu A, Dunn JM, Darrah RJ, Dorfman R, Sandford AJ, Corey M, Zielenski J, Durie P, Goddard K, Yankaskas JR, Wright FA, Knowles MR; Gene Modifier Study Group. Genetic modifiers of lung disease in cystic fibrosis. N Engl J Med. 2005 Oct 6;353(14):1443-53. doi: 10.1056/NEJMoa051469. — View Citation

O'Neal WK, Gallins P, Pace RG, Dang H, Wolf WE, Jones LC, Guo X, Zhou YH, Madar V, Huang J, Liang L, Moffatt MF, Cutting GR, Drumm ML, Rommens JM, Strug LJ, Sun W, Stonebraker JR, Wright FA, Knowles MR. Gene expression in transformed lymphocytes reveals variation in endomembrane and HLA pathways modifying cystic fibrosis pulmonary phenotypes. Am J Hum Genet. 2015 Feb 5;96(2):318-28. doi: 10.1016/j.ajhg.2014.12.022. Epub 2015 Jan 29. — View Citation

Polineni D, Dang H, Gallins PJ, Jones LC, Pace RG, Stonebraker JR, Commander LA, Krenicky JE, Zhou YH, Corvol H, Cutting GR, Drumm ML, Strug LJ, Boyle MP, Durie PR, Chmiel JF, Zou F, Wright FA, O'Neal WK, Knowles MR. Airway Mucosal Host Defense Is Key to Genomic Regulation of Cystic Fibrosis Lung Disease Severity. Am J Respir Crit Care Med. 2018 Jan 1;197(1):79-93. doi: 10.1164/rccm.201701-0134OC. — View Citation