A Novel Assay to Quantify Treatment Response in Cystic Fibrosis (CF)

A Novel Assay to Quantify Treatment Response in CF

Inflammation is present in the Cystic fibrosis (CF) airway from the time of infancy, and worsens with the onset of chronic infection. Therapies with proven benefit are associated with decreased airway inflammation. Thus, sensitive and reproducible biomarkers of airway inflammation have long been sought as a necessary component to improved clinical care and to facilitate therapeutic trials for CF. FEV1, the standard outcome measure in CF, is recognized as an insensitive outcome measure. the investigators have identified a panel of 10 genes which sensitively predict resolution of pulmonary inflammation, in response to therapy of an acute pulmonary exacerbation. With the goal of yielding a technically simple but unique CF biomarker assay, the investigators have tested whether proteins signified by these genes show large changes in expression following treatment of acute pulmonary exacerbations. Protein quantifications are among the most common measurements performed in clinical laboratories around the world. Based on preliminary findings that changes in white blood cell proteins mirror changes seen in the genes, the investigators propose to identify top candidate proteins, from the investigators gene panel, which change in response to exacerbation therapy. Once identified, these proteins will be quantified directly with a new blood test which is inexpensive and simple to perform. The investigators propose to validate this blood test in a single site trial. If successful, this proposal will yield a biomarker assay that will be available to validate in a multi-site trial and provide unique insights into mechanisms that regulate white blood cell activation and recruitment in CF lung disease.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis

• Study Type: Observational
• Enrollment (Actual): 122

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health

Participation Criteria

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

Adult CF patients > 18 years of age undergoing treatment for acute pulmonary exacerbation

Description

Inclusion Criteria:

1. Documented diagnosis of CF.
2. Age 18 years old or greater.
3. Presentation at the start of treatment for a pulmonary exacerbation of CF.
4. Ability to perform reproducible Pulmonary Function Tests and produce sputum.
5. Willingness to comply with study procedure and willingness to provide written consent.

Exclusion Criteria:

1. 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.
2. Use of systemic steroids

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in leukocyte associated protein expression by flow cytometry and by leukocyte specific ELISA in response to acute exacerbation therapy	10-21 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in FEV1 in response to acute exacerbation therapy	10-21 days
Change in sputum IL-8 and neutrophil elastase in response to acute exacerbation therapy	10-21 days
Change in bacterial density in response to exacerbation therapy	10-21 days
Change in CRP in response to acute exacerbation therapy	10-21 days
Time to next exacerbation	up to 3 years

Collaborators and Investigators

• Sponsor: Milene Saavedra
• Collaborators: Cystic Fibrosis Foundation

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (ACTUAL): January 1, 2018
• Study Completion (ACTUAL): January 1, 2018

Study Registration Dates

• First Submitted: June 20, 2012
• First Submitted That Met QC Criteria: June 21, 2012
• First Posted (ESTIMATE): June 22, 2012

Study Record Updates

• Last Update Posted (ACTUAL): March 23, 2020
• Last Update Submitted That Met QC Criteria: March 20, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: SAAVED11A0

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