Detection of Reductions in Cystic Fibrosis Airway Inflammation While Using Aztreonam Lysine Solution

Ultrasensitive Detection of Reductions in Cystic Fibrosis Airway Inflammation While Using Aztreonam Lysine for Inhalation Solution

In cystic fibrosis, there is a critical need for better predictors of treatment response. The investigators have identified a panel of white blood cell biomarkers which can be directly measured as a blood test in subjects with cystic fibrosis. These biomarkers predict reduction of airway inflammation and infection more accurately than lung function testing, in patients receiving intravenous antibiotic therapy. In the current study, we hypothesize that this panel of gene biomarkers which can be readily measured from peripheral blood will sensitively predict changes in inflammation when patients receive inhaled antibiotic therapy, specifically Cayston (or inhaled aztreonam lysine). Patients enrolled in the study will have blood drawn before and after a month of inhaled Cayston, in order to test whether genes predict response to Cayston therapy more robustly than do standard measures such as lung function tests.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis in Adults, Chronic Colonization With Pseudomonas Aeruginosa

• Study Type: Observational
• Enrollment (Actual): 23

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 to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Enrolled subjects will include adults with cystic fibrosis, over the age of 18 years, who are at baseline health and colonized with Pseudomonas aeruginosa, and who are newly prescribed Cayston (aztreonam lysine) for inhalation, or who are resuming use of this drug after 28 days off of inhaled antimicrobial agents with activity against Pseudomonas aeruginosa.

Description

Inclusion Criteria:

• Documented diagnosis of cystic fibrosis
• Age 18 years old or greater
• FEV1 percent predicted greater than 25%
• Ability to perform reproducible pulmonary function tests and produce sputum spontaneously
• Chronic bacterial colonization with Pseudomonas aeruginosa with 2 positive cultures in previous 2 years.
• Chronically stable pulmonary condition without evidence of acute pulmonary exacerbation within 14 days prior to screening
• Starting Cayston cycle as part of clinical care.

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.
• Aztreonam allergy, bronchospasm or other contraindication to use of aztreonam.
• Signs and symptoms of acute pulmonary exacerbation at the time of enrollment or during study.
• Active infection and treatment for non-tuberculous mycobacteria.
• Concomitant use of systemic steroids.
• Use of inhaled antimicrobial agents with activity against Pseudomonas aeruginosa within 28 days prior to Visit 1.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
CF adults colonized with Pseudomonas aeruginosa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gene biomarker panel	Measurement of gene biomarkers by polymerase chain reaction before and after 1 month of Cayston therapy	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Forced expiratory volume in 1 second (FEV1)	Change in pulmonary function (FEV1) after one month of Cayston therapy	1 month
Sputum Bacterial Density	Change in sputum bacterial density after one month of Cayston	1 month
C-reactive protein	Change in C-reactive protein after one month of Cayston	1 month
Interleukin 8	Change in serum and sputum interleukin 8 concentrations after one month of Cayston	1 month
Patient reported symptom scores	Change in patient reported symptoms after one month of Cayston	1 month

Collaborators and Investigators

• Sponsor: National Jewish Health

Publications and helpful links

General Publications

• Caceres SM, Sanders LA, Rysavy NM, Poch KR, Jones CR, Pickard K, Fingerlin TE, Marcus RA, Malcolm KC, Taylor-Cousar JL, Nichols DP, Nick JA, Strand M, Saavedra MT. Blood mRNA biomarkers distinguish variable systemic and sputum inflammation at treatment initiation of inhaled antibiotics in cystic fibrosis: A prospective non-randomized trial. PLoS One. 2022 May 5;17(5):e0267592. doi: 10.1371/journal.pone.0267592. eCollection 2022.

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): July 27, 2017
• Study Completion (Actual): July 27, 2017

Study Registration Dates

• First Submitted: November 15, 2012
• First Submitted That Met QC Criteria: November 26, 2012
• First Posted (Estimate): November 29, 2012

Study Record Updates

• Last Update Posted (Actual): March 24, 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; Inflammation; Cystic Fibrosis
• Other Study ID Numbers: IN-US-205-0171

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No