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Trial record 2 of 11 for:    Genetic Modifiers Lung

Gene Modifiers of Cystic Fibrosis Lung Disease

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill Identifier:
First received: May 20, 2002
Last updated: September 13, 2017
Last verified: September 2017
The purpose of this study is to examine genetic modifiers of the severity of cystic fibrosis lung disease.

Cystic Fibrosis Lung Diseases

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Gene Modifiers of Cystic Fibrosis Lung Disease

Resource links provided by NLM:

Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • This is not an interventional study. [ Time Frame: This is not an interventional study ]
    Not applicable. This is not an interventional study.

Estimated Enrollment: 600
Study Start Date: September 2001
Estimated Study Completion Date: July 2018
Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)
Detailed Description:


Cystic Fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene resulting in impaired chloride transport across epithelial cells. While many organs are involved, infection, inflammation and destruction of the lungs ultimately result in morbidity and mortality. There is an association between residual CFTR function and severity of disease, however there is great variability within specific mutations suggesting gene modifiers. Even though there are over 900 mutations in CFTR that are related to CF lung disease, F508 the most common one is represented in 70 percent of the American CF population. Thus, establishing a phenotype/genotype correlation using homozygote F508 patients is likely to identify genes that are responsible for a mild form of disease. Why is this important? Whereas since the identification of the gene CFTR a significant amount of knowledge has been accumulated on CFTR function and CF pathogenesis, the cure for CF (treated as a monogenic disease) has been elusive. Identification of genetic modifiers (that may explain why 10 percent of CF patients died before the age of 10, 1/3 before the age of 20 while 50 percent live over 32 years of age) should expand the therapeutic targets that may lead to shifting of the severe phenotypes to milder ones. Moreover, the approach outlined in this study may also result in a better understanding of CFTR and delta F508 biogenesis and function, as it may identify genes directly related to CFTR.

The study is in response to a Request for Applications titled "Genetic Modifiers of Single Gene Defect Diseases" released in August, 2000 and co-sponsored by the National Institute of Diabetes, Digestive, and Kidney Diseases.


Patients with cystic fibrosis (CF) display a wide range of disease severity, particularly in pulmonary phenotype. Although some of this variability can be attributed to specific mutations within the CFTR gene (allelic heterogeneity), much of this variability has not been adequately explained. The central hypothesis of the study is that much of the "severity" (or "mildness") of CF lung disease reflects the influence of non-CFTR "modifier" alleles (genes). The study is designed to identify associations between non-CFTR genes and the pulmonary phenotype. To accomplish this goal, studies will be conducted on 600 CF patients who have the same CFTR genetic background, i.e., homozygous deltaF508, and who are at the extremes of pulmonary phenotype, i.e., the most severe and mildest lung disease. Pulmonary disease severity (or mildness) will be quantitated by longitudinal lung function analysis with informative censoring. The overall strategy will be to test for the association of candidate modifier alleles (genes) with the severity (or mildness) of pulmonary disease. Key clinical features (gender; age-at-diagnosis; sweat chloride; nutrition; and respiratory microbiology) will be important variables in the overall analysis. Initially, the study will test candidate genes (n=200) that have been implicated in the pathophysiology of CF lung disease. A pooling strategy will be used to expedite the first rounds of testing. After pooling DNA from the "severe" patients, and pooling DNA from the mild patients, those genes (alleles) can be identified with the greatest association with phenotype. Follow-up genotyping in individual subjects will allow subgroup analyses (gender; age-at-diagnosis; nutrition; respiratory microbiology) for each gene, as well as more complex analyses to search for interaction among different alleles. Subsequent studies will involve genome-wide testing with single nucleotide polymorphisms (SNPs) to identify loci (and genes) that are not present in the initial list of candidate genes. Identification of genes that modulate the severity of the pulmonary phenotype will improve understanding of the pathophysiology of CF lung disease, and identify new targets for therapeutic intervention.


Ages Eligible for Study:   up to 100 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
CF patients who have the same CFTR genetic background, i.e., homozygous deltaF508, and who are at the extremes of pulmonary phenotype, i.e., the most severe and mildest lung disease.

Inclusion Criteria:

  • Diagnosed with CF
  Contacts and Locations
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Please refer to this study by its identifier: NCT00037765

United States, North Carolina
Chapel Hill, North Carolina, United States, 27599-7600
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Principal Investigator: Michael Knowles University of North Carolina
  More Information

Additional Information:

Responsible Party: University of North Carolina, Chapel Hill Identifier: NCT00037765     History of Changes
Other Study ID Numbers: 5R01HL068890 ( U.S. NIH Grant/Contract )
Study First Received: May 20, 2002
Last Updated: September 13, 2017

Additional relevant MeSH terms:
Cystic Fibrosis
Lung Diseases
Pulmonary Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases processed this record on September 19, 2017