IL-17 Neutrophils in CF Lung Inflammation

January 29, 2019 updated by: James F. Chmiel, University Hospitals Cleveland Medical Center

The Role of IL-17 Neutrophils in CF Lung Inflammation

The purpose of this study is to determine whether IL-17 polymorphonuclear leukocytes (PMNs) are central to the disease pathology in CF. This will be determined by demonstrating that IL-17 PMNs are present in the CF airway, correlate with lung function measures, and decrease in patients being treated with IV antibiotics for a pulmonary exacerbation.

Study Overview

Status

Completed

Conditions

Detailed Description

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

Enrollment (Actual)

14

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Rainbow Babies and Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients seen in the cystic fibrosis outpatient clinic (Clinically Stable Cohort) and inpatient unit (Exacerbation/IV Antibiotics Cohort) of Cystic Fibrosis Center in Cleveland, OH (Rainbow Babies and Children's Hospital/University Hospitals Case Medical Center)

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
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
Exacerbation
Patients with cystic fibrosis admitted for treatment of a pulmonary exacerbation with IV antibiotics, 10 subjects with one copy of F508del

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Samples will be obtained at one outpatient clinic visit during the next calendar year
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
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospitals Cleveland Medical Center

Collaborators

Case Western Reserve University

Investigators

  • Principal Investigator: James F. Chmiel, MD, MPH, Rainbow Babies and Children's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2014

Primary Completion (Actual)

December 1, 2014

Study Completion (Actual)

December 1, 2014

Study Registration Dates

First Submitted

December 18, 2013

First Submitted That Met QC Criteria

December 29, 2013

First Posted (Estimate)

January 1, 2014

Study Record Updates

Last Update Posted (Actual)

February 15, 2019

Last Update Submitted That Met QC Criteria

January 29, 2019

Last Verified

January 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 01CH2013

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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.

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