IL-17 Neutrophils in CF Lung Inflammation
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| ClinicalTrials.gov Identifier: NCT02025829 |
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Recruitment Status :
Completed
First Posted : January 1, 2014
Results First Posted : March 24, 2017
Last Update Posted : February 15, 2019
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| Condition or disease |
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| Cystic Fibrosis |
This study consists of two parts which will be conducted in parallel. In the first part of the study, 14 subjects will be recruited for the Clinically Stable Cohort. Subjects will be asked to provide 1 gm of expectorated sputum and 40-ml of blood. A cell count and differential will be performed on the sputum followed by analysis for IL-17 PMNs by fluorescence-activated cell sorter (FACS). IL-17 PMNs also will be isolated by running the remainder of the cell pellet through a column of magnetic beads designed for this purpose. These neutrophils will be lysed and intracellular cytokines determined. Sputum supernatants will be stored frozen until analyzed for the presence of IL-1β, IL-6, IL-8, IL-17A, TGF-β, TNF-α, and neutrophil elastase. Clinical data will be captured from the subject's clinical outpatient visit including lung function measures and clinical culture results. IL-17 PMNs will be correlated with lung function measures and inflammatory mediators at baseline.
In the second part of this study, 10 subjects will be recruited for the Exacerbation Cohort. Subjects will provide at least 1 gram of expectorated sputum and 40-ml of blood within 72 hours of hospital admission. Sputum and blood will be processed and analyzed as described above. Sputum and blood also will be obtained at the end of treatment (within 72 hours of completion of IV antibiotics) when the subject is at his or her baseline as determined by the managing physician. Clinical data will be captured from the subject's hospitalization records including lung function measures and clinical culture results.
| Study Type : | Observational |
| Actual Enrollment : | 14 participants |
| Observational Model: | Case-Only |
| Time Perspective: | Prospective |
| Official Title: | The Role of IL-17 Neutrophils in CF Lung Inflammation |
| Study Start Date : | February 2014 |
| Actual Primary Completion Date : | December 2014 |
| Actual Study Completion Date : | December 2014 |
| Group/Cohort |
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Clinically Stable
Patients with cystic fibrosis and are clinically stable, 10 subjects with one copy of F508del and 4 subjects with at least one copy of G551D
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Exacerbation
Patients with cystic fibrosis admitted for treatment of a pulmonary exacerbation with IV antibiotics, 10 subjects with one copy of F508del
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- Change in Sputum IL-17 Neutrophils [ Time Frame: End of Treatment, two weeks. Samples will be obtained from each study volunteer at the beginning of IV antibiotic treatment and at the completion of antibiotic treatment for a pulmonary exacerbation ]In the Exacerbation/IV Antibiotics Cohort--Subjects will serve as their own controls. The percentage of neutrophils (in sputum) positive for IL-17 was determined by flow cytometry for each subject at the beginning and end of treatment for a pulmonary exacerbation. Sputum IL-17 neutrophil counts will be compared to the change in lung function (FEV1) as determined by spirometry (American Thoracic Society standards).
- Sputum Inflammatory Mediators: IL-1β, IL-6, IL-8, IL-17A, TGF-β, TNF-α, and Neutrophil Elastase [ Time Frame: Samples will be obtained at one outpatient clinic visit during the next calendar year ]In the Clinically Stable Cohort--Measurement of sputum inflammatory mediators: IL-1β, IL-6, IL-8, IL-17A, TGF-β, TNF-α, and neutrophil elastase
- Sputum Inflammatory Mediators: IL-1β, IL-6, IL-8, IL-17A, and Neutrophil Elastase [ Time Frame: End of Treatment, two weeks. Samples will be obtained from each study volunteer at the beginning of IV antibiotic treatment and at the completion of antibiotic treatment for a pulmonary exacerbation ]In the Exacerbation/IV Antibiotics Cohort--Measurement of sputum inflammatory mediators by multiplex assay for IL-1β, IL-6, IL-8, and IL-17A. Neutrophil elastase determined by colorimetric assay. Measurements at the beginning of IV antibiotic treatment and after 2 weeks antibiotic treatment for a pulmonary exacerbation
Biospecimen Retention: Samples With DNA
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| Ages Eligible for Study: | 18 Years to 50 Years (Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
| Sampling Method: | Non-Probability Sample |
Inclusion Criteria:
- For Both Cohorts: ≥ 18 < 50 years of age
- For Both Cohorts: Must have a documented diagnosis of CF (positive sweat chloride ≥60 milliequivalents (mEq)/liter, by pilocarpine iontophoresis) and/or a genotype with two identifiable mutations consistent with CF accompanied by one or more clinical features with the CF) phenotype
- For Both Cohorts: Chronically infected with P. aeruginosa defined by 2 positive cultures in the past year or 3 in the last two years
- For Both Cohorts: Ability to expectorate mucus
- For Both Cohorts: Ability to provide written informed consent
- For Clinically Stable Cohort: 4 subjects with one copy of G551D
- For Clinically Stable Cohort: 10 subjects who do not have G551D, they must have one copy of F508del
- For Clinically Stable Cohort: CF subjects must have a baseline FEV1 percent predicted > 50% (in the last year, obtained from medical record)
- For Clinically Stable Cohort: Clinically stable: free of any acute illness for >14 days
- For Clinically Stable Cohort: Must have performed spirometry for clinical purposes at that clinical visit
- For Clinically Stable Cohort: Must have a sputum culture sent to the clinical lab for clinical purposes at the time of the study visit
- For Clinically Stable Cohort: Have not been prescribed any new systemic antibiotics for the 14 days prior to enrollment
- For Exacerbation/IV Antibiotics Cohort: One copy of F508del
- For Exacerbation/IV Antibiotics Cohort: Must have a doctor defined pulmonary exacerbation requiring treatment with IV antibiotics
- For Exacerbation/IV Antibiotics Cohort: Must have performed spirometry for clinical purposes within 72 hours of initiating IV antibiotics and within 72 hours of completing IV antibiotics
- For Exacerbation/IV Antibiotics Cohort: Must have a sputum culture sent to the clinical lab for clinical purposes within 72 hours of admission
Exclusion Criteria:
- For Both Cohorts: Pregnancy (based on self-report)
- For Both Cohorts: Co-infection with Burkholderia cepacia complex organisms
- For Both Cohorts: Any condition that in the opinion of the subject or the subject's managing physician that would compromise that individuals ability to participate in these studies
- For Both Cohorts: Inability to tolerate the study procedures
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02025829
| United States, Ohio | |
| Rainbow Babies and Children's Hospital | |
| Cleveland, Ohio, United States, 44106 | |
| Principal Investigator: | James F. Chmiel, MD, MPH | Rainbow Babies and Children's Hospital |
| Responsible Party: | James F. Chmiel, Associate Professor of Pediatrics, University Hospitals Cleveland Medical Center |
| ClinicalTrials.gov Identifier: | NCT02025829 |
| Other Study ID Numbers: |
01CH2013 |
| First Posted: | January 1, 2014 Key Record Dates |
| Results First Posted: | March 24, 2017 |
| Last Update Posted: | February 15, 2019 |
| Last Verified: | January 2019 |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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cystic fibrosis IL-17 neutrophils |
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Cystic Fibrosis Pneumonia Fibrosis Inflammation Pathologic Processes Pancreatic Diseases |
Digestive System Diseases Lung Diseases Respiratory Tract Diseases Genetic Diseases, Inborn Infant, Newborn, Diseases Respiratory Tract Infections |