Utility of CD64 and TLR2 Assays to Diagnose Acute Pulmonary Exacerbations in Cystic Fibrosis

NCT04397809 | Completed

• 1 other identifier: 14BGF-10
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (3)

• Difference in neutrophil CD64 expression

  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).

  Within 24 hours of initiation of IV antibiotic treatment for CF pulmonary exacerbation or at Baseline health

• Difference in CD4+ T cell TLR2 expression

  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).

  Within 24 hours of initiation of IV antibiotic treatment for CF pulmonary exacerbation or at Baseline health

• Difference in GILT expression

  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).

  Within 24 hours of initiation of IV antibiotic treatment for CF pulmonary exacerbation or at Baseline health

Secondary Outcomes (6)

• Correlation of primary outcome measurements with lung function tests

  Within 24 hours of initiation of IV antibiotic treatment for CF pulmonary exacerbation or at Baseline health

• Correlation of primary outcome measurements with C-Reactive Protein

  Within 24 hours of initiation of IV antibiotic treatment for CF pulmonary exacerbation or at Baseline health

• Correlation of primary outcome measurements with total white blood cell counts

  Within 24 hours of initiation of IV antibiotic treatment for CF pulmonary exacerbation or at Baseline health

• Correlation of primary outcome measurements with sputum inflammatory markers

  Within 24 hours of initiation of IV antibiotic treatment for CF pulmonary exacerbation or at Baseline health

• Correlation of primary outcome measurements with phagocytosis

  Within 24 hours of initiation of IV antibiotic treatment for CF pulmonary exacerbation or at Baseline health

Study Arms (2)

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.

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Jewish Health: lead

Study Sites (1)

National Jewish Health

Denver, Colorado, 80206, United States

Location

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2020
• First Posted: May 21, 2020
• Study Start: September 10, 2014
• Primary Completion: May 23, 2019
• Study Completion: August 31, 2021
• Last Updated: September 2, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)