- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04397809
Utility of CD64 and TLR2 Assays to Diagnose Acute Pulmonary Exacerbations in Cystic Fibrosis
August 31, 2021 updated by: National Jewish Health
Cystic fibrosis (CF) is the most common inherited disease in the western world.
On a yearly basis, 56% of CF patients, or nearly 17,000 individuals in the US, suffer from acute pulmonary exacerbations (APE).
The purpose of this study is to test a candidate assay for its ability to diagnose APE, the most important disease event in CF.
While previous studies have been able to identify biomarkers of CF prognosis and risk stratification, three markers have demonstrated characteristics ideal for APE diagnosis: CD64, TLR2, and GILT.
CD64 is a cellular receptor, expressed on numerous cells of the immune system, whose role is to bind antibodies which are attached to infected cells or pathogens.
TLR2 plays a major role in early host-microbial interactions.
GILT has been shown to be more precise in targeting immune responses against antigens and influences T lymphocyte response.
This study looks to identify the differences in the expression of neutrophil CD64 and CD4+ T cell TLR2 and GILT between acute illness and baseline health as a sensitive marker of acute pulmonary exacerbation so that it may facilitate rapid hematologic diagnosis of the condition.
The study also looks to compare sensitivity and specificity of the assays above to standard measures, such as health related quality of life scores (CFQ-R), loss of lung function, white blood cell counts and CRP, for diagnosing acute exacerbations.
Study Overview
Status
Completed
Conditions
Study Type
Observational
Enrollment (Actual)
150
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
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Colorado
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Denver, Colorado, United States, 80206
- National Jewish Health
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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 and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Sampling Method
Probability Sample
Study Population
CF patients aged 18 years or older at the time of an acute pulmonary exacerbation or at baseline health who are followed by the Adult CF Program at National Jewish Health will be eligible to enroll in this study.
Description
Inclusion Criteria:
- Documented diagnosis of CF.
- Age 18 years old or greater.
- Presentation at baseline health OR at the start of treatment for a pulmonary exacerbation of CF.
- Ability to perform reproducible Pulmonary Function Tests
- Ability to produce sputum.
- Willingness to complete a health-related quality of life questionnaire
- Willingness to comply with study procedure and provide written consent.
Exclusion Criteria:
• Presence of a condition or abnormality that, in the opinion of the Principal Investigator (PI), would compromise the safety of the patient or the quality of the data.
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
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
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Acute Pulmonary Exacerbation (APE)
Those subjects presenting with APE will be treated with at least two pathogen specific I.V. antibiotics, as dictated by their treating physician and compliant with standard guidelines for care of an APE.
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Baseline Health
Those subjects presenting at baseline health will be identified by their treating physician as such and will not be starting on any treatments for APE.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Difference in neutrophil CD64 expression
Time Frame: Within 24 hours of initiation of IV antibiotic treatment for CF pulmonary exacerbation or at Baseline health
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The primary outcome measure is the difference in expression of neutrophil CD64 as measured by flow cytometry from circulating blood between the two groups (APE and baseline).
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Within 24 hours of initiation of IV antibiotic treatment for CF pulmonary exacerbation or at Baseline health
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Difference in CD4+ T cell TLR2 expression
Time Frame: Within 24 hours of initiation of IV antibiotic treatment for CF pulmonary exacerbation or at Baseline health
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The primary outcome measure is the difference in expression of CD4+ T cell TLR2 as measured by flow cytometry from circulating blood between the two groups (APE and baseline).
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Within 24 hours of initiation of IV antibiotic treatment for CF pulmonary exacerbation or at Baseline health
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Difference in GILT expression
Time Frame: Within 24 hours of initiation of IV antibiotic treatment for CF pulmonary exacerbation or at Baseline health
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The primary outcome measure is the difference in expression of GILT as measured by flow cytometry from circulating blood between the two groups (APE and baseline).
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Within 24 hours of initiation of IV antibiotic treatment for CF pulmonary exacerbation or at Baseline health
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Correlation of primary outcome measurements with lung function tests
Time Frame: Within 24 hours of initiation of IV antibiotic treatment for CF pulmonary exacerbation or at Baseline health
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A secondary outcome measure is the correlation of the differences in expression of neutrophil CD64, CD4+ T cell TLR2, and GILT with changes in FEV1 as measured by spirometry.
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Within 24 hours of initiation of IV antibiotic treatment for CF pulmonary exacerbation or at Baseline health
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Correlation of primary outcome measurements with C-Reactive Protein
Time Frame: Within 24 hours of initiation of IV antibiotic treatment for CF pulmonary exacerbation or at Baseline health
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A secondary outcome measure is the correlation of the differences in expression of neutrophil CD64, CD4+ T cell TLR2, and GILT with differences in C-Reactive Protein (CRP)
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Within 24 hours of initiation of IV antibiotic treatment for CF pulmonary exacerbation or at Baseline health
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Correlation of primary outcome measurements with total white blood cell counts
Time Frame: Within 24 hours of initiation of IV antibiotic treatment for CF pulmonary exacerbation or at Baseline health
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A secondary outcome measure is the correlation of the differences in expression of neutrophil CD64, CD4+ T cell TLR2, and GILT with differences in total white blood cell counts (WBC).
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Within 24 hours of initiation of IV antibiotic treatment for CF pulmonary exacerbation or at Baseline health
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Correlation of primary outcome measurements with sputum inflammatory markers
Time Frame: Within 24 hours of initiation of IV antibiotic treatment for CF pulmonary exacerbation or at Baseline health
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A secondary outcome measure is the correlation of the differences in expression of neutrophil CD64, CD4+ T cell TLR2, and GILT with differences in sputum inflammatory markers as measured by sputum neutrophil counts and neutrophil elastase expression.
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Within 24 hours of initiation of IV antibiotic treatment for CF pulmonary exacerbation or at Baseline health
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Correlation of primary outcome measurements with phagocytosis
Time Frame: Within 24 hours of initiation of IV antibiotic treatment for CF pulmonary exacerbation or at Baseline health
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A secondary outcome measure is the correlation of the differences in expression of neutrophil CD64, CD4+ T cell TLR2, and GILT with differences in the percentage of phagocytosis by isolated neutrophils.
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Within 24 hours of initiation of IV antibiotic treatment for CF pulmonary exacerbation or at Baseline health
|
Correlation of primary outcome measurements with quality of life questionnaire score
Time Frame: Within 24 hours of initiation of IV antibiotic treatment for CF pulmonary exacerbation or at Baseline health
|
A secondary outcome measure is the correlation of the differences in expression of neutrophil CD64, CD4+ T cell TLR2, and GILT with differences in patient reported health related quality of life scores as measured by the Cystic Fibrosis Questionnaire-Revised (CFQ-R).
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Within 24 hours of initiation of IV antibiotic treatment for CF pulmonary exacerbation or at Baseline health
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
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 (Actual)
September 10, 2014
Primary Completion (Actual)
May 23, 2019
Study Completion (Actual)
August 31, 2021
Study Registration Dates
First Submitted
May 18, 2020
First Submitted That Met QC Criteria
May 18, 2020
First Posted (Actual)
May 21, 2020
Study Record Updates
Last Update Posted (Actual)
September 2, 2021
Last Update Submitted That Met QC Criteria
August 31, 2021
Last Verified
August 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 14BGF-10
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
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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