Cystic FibrosisNCT02025829
IL-17 Neutrophils in CF Lung Inflammation
An observational study of Cystic Fibrosis, run by University Hospitals Cleveland Medical Center at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Cystic Fibrosis
- Type of treatment
- Injection or infusion
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2014to Dec 2014
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
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)
Who may be able to join
- 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
Show all 16Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Rainbow Babies and Children's Hospital
Cleveland, Ohio, 44106
About this study
Official title: 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.
Read the 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.
- Conditions
- Cystic Fibrosis
- Keywords
- cystic fibrosis, IL-17 neutrophils
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 being measured
The primary outcome is the main question the study is designed to answer.
Change in Sputum IL-17 Neutrophils
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).
Measured: 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 outcomes (2)
Sputum Inflammatory Mediators: IL-1β, IL-6, IL-8, IL-17A, TGF-β, TNF-α, and Neutrophil Elastase
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
Measured: 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
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
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jan 2014 (estimated)
- Study startFeb 2014
- Primary completionDec 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by University Hospitals Cleveland Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospitals Cleveland Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Case Western Reserve University
- Responsible party
- Principal investigator, James F. Chmiel, University Hospitals Cleveland Medical Center
- Investigators
- James F. Chmiel, MD, MPH, Principal investigator, Rainbow Babies and Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02025829
- Sponsor's protocol ID
- 01CH2013
- Status last verified
- Jan 2019
- First submitted
- 18 Dec 2013
- Last updated
- 15 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Chmiel JF, Berger M, Konstan MW. The role of inflammation in the pathophysiology of CF lung disease. Clin Rev Allergy Immunol. 2002 Aug;23(1):5-27. doi: 10.1385/CRIAI:23:1:005.
PubMed 12162106Lands LC, Stanojevic S. Oral non-steroidal anti-inflammatory drug therapy for lung disease in cystic fibrosis. Cochrane Database Syst Rev. 2013 Jun 13;(6):CD001505. doi: 10.1002/14651858.CD001505.pub3.
PubMed 23765216Flume PA, O'Sullivan BP, Robinson KA, Goss CH, Mogayzel PJ Jr, Willey-Courand DB, Bujan J, Finder J, Lester M, Quittell L, Rosenblatt R, Vender RL, Hazle L, Sabadosa K, Marshall B; Cystic Fibrosis Foundation, Pulmonary Therapies Committee. Cystic fibrosis pulmonary guidelines: chronic medications for maintenance of lung health. Am J Respir Crit Care Med. 2007 Nov 15;176(10):957-69. doi: 10.1164/rccm.200705-664OC. Epub 2007 Aug 29.
PubMed 17761616Oermann CM, Sockrider MM, Konstan MW. The use of anti-inflammatory medications in cystic fibrosis: trends and physician attitudes. Chest. 1999 Apr;115(4):1053-8. doi: 10.1378/chest.115.4.1053.
PubMed 10208207Konstan MW. Ibuprofen therapy for cystic fibrosis lung disease: revisited. Curr Opin Pulm Med. 2008 Nov;14(6):567-73. doi: 10.1097/MCP.0b013e32831311e8.
PubMed 18812834Konstan MW, Byard PJ, Hoppel CL, Davis PB. Effect of high-dose ibuprofen in patients with cystic fibrosis. N Engl J Med. 1995 Mar 30;332(13):848-54. doi: 10.1056/NEJM199503303321303.
PubMed 7503838Konstan MW, Schluchter MD, Xue W, Davis PB. Clinical use of Ibuprofen is associated with slower FEV1 decline in children with cystic fibrosis. Am J Respir Crit Care Med. 2007 Dec 1;176(11):1084-9. doi: 10.1164/rccm.200702-181OC. Epub 2007 Sep 13.
PubMed 17872492Chmiel JF, Konstan MW. Inflammation and anti-inflammatory therapies for cystic fibrosis. Clin Chest Med. 2007 Jun;28(2):331-46. doi: 10.1016/j.ccm.2007.02.002.
PubMed 17467552Taylor PR, Roy S, Leal SM Jr, Sun Y, Howell SJ, Cobb BA, Li X, Pearlman E. Activation of neutrophils by autocrine IL-17A-IL-17RC interactions during fungal infection is regulated by IL-6, IL-23, RORgammat and dectin-2. Nat Immunol. 2014 Feb;15(2):143-51. doi: 10.1038/ni.2797. Epub 2013 Dec 22.
PubMed 24362892
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of IL-17 Neutrophils in CF Lung Inflammation
- ClinicalTrials.gov ID
- NCT02025829
- Acronym / sponsor ID
- 01CH2013
- Conditions
- Cystic Fibrosis
- Keywords
- cystic fibrosis, IL-17 neutrophils
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- University Hospitals Cleveland Medical CenterUniversity, hospital or other
- Collaborators
- Case Western Reserve University
- Study start
- Feb 2014
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 1 Jan 2014 (estimated)
- Results
- Posted 24 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- 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)
Key inclusion criteria (16 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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).
2 secondary outcomes
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 12162106Chmiel JF, Berger M, Konstan MW. The role of inflammation in the pathophysiology of CF lung disease. Clin Rev Allergy Immunol. 2002 Aug;23(1):5-27. doi: 10.1385/CRIAI:23:1:005.
- Background: PubMed 23765216Lands LC, Stanojevic S. Oral non-steroidal anti-inflammatory drug therapy for lung disease in cystic fibrosis. Cochrane Database Syst Rev. 2013 Jun 13;(6):CD001505. doi: 10.1002/14651858.CD001505.pub3.
- Background: PubMed 17761616Flume PA, O'Sullivan BP, Robinson KA, Goss CH, Mogayzel PJ Jr, Willey-Courand DB, Bujan J, Finder J, Lester M, Quittell L, Rosenblatt R, Vender RL, Hazle L, Sabadosa K, Marshall B; Cystic Fibrosis Foundation, Pulmonary Therapies Committee. Cystic fibrosis pulmonary guidelines: chronic medications for maintenance of lung health. Am J Respir Crit Care Med. 2007 Nov 15;176(10):957-69. doi: 10.1164/rccm.200705-664OC. Epub 2007 Aug 29.
- Background: PubMed 10208207Oermann CM, Sockrider MM, Konstan MW. The use of anti-inflammatory medications in cystic fibrosis: trends and physician attitudes. Chest. 1999 Apr;115(4):1053-8. doi: 10.1378/chest.115.4.1053.
- Background: PubMed 18812834Konstan MW. Ibuprofen therapy for cystic fibrosis lung disease: revisited. Curr Opin Pulm Med. 2008 Nov;14(6):567-73. doi: 10.1097/MCP.0b013e32831311e8.
- Background: PubMed 7503838Konstan MW, Byard PJ, Hoppel CL, Davis PB. Effect of high-dose ibuprofen in patients with cystic fibrosis. N Engl J Med. 1995 Mar 30;332(13):848-54. doi: 10.1056/NEJM199503303321303.
- Background: PubMed 17872492Konstan MW, Schluchter MD, Xue W, Davis PB. Clinical use of Ibuprofen is associated with slower FEV1 decline in children with cystic fibrosis. Am J Respir Crit Care Med. 2007 Dec 1;176(11):1084-9. doi: 10.1164/rccm.200702-181OC. Epub 2007 Sep 13.
- Background: PubMed 17467552Chmiel JF, Konstan MW. Inflammation and anti-inflammatory therapies for cystic fibrosis. Clin Chest Med. 2007 Jun;28(2):331-46. doi: 10.1016/j.ccm.2007.02.002.
- Background: PubMed 24362892Taylor PR, Roy S, Leal SM Jr, Sun Y, Howell SJ, Cobb BA, Li X, Pearlman E. Activation of neutrophils by autocrine IL-17A-IL-17RC interactions during fungal infection is regulated by IL-6, IL-23, RORgammat and dectin-2. Nat Immunol. 2014 Feb;15(2):143-51. doi: 10.1038/ni.2797. Epub 2013 Dec 22.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James F. Chmiel, MD, MPH principal investigator
Rainbow Babies and Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cystic Fibrosis, run by University Hospitals Cleveland Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02025829, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2019.