Biomarkers of Iron Homeostasis and Responses to Cystic Fibrosis Pulmonary Exacerbation (CFPE) Treatment

Study Overview
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Brief Summary
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The goal of this study is to identify chemical compounds in the blood and sputum (i.e., biomarkers) that are associated with objective measurements of health status in patients with cystic fibrosis (CF). This study builds upon observations that blood levels of hepcidin-25, a protein that regulates how the body uses and stores iron, vary during CF pulmonary exacerbation (CFPE).

Official Title
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Do Changes in Serum Hepcidin-25 Concentration Predict Cystic Fibrosis Pulmonary Exacerbation (CFPE) Treatment Responses?

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Other: Adults - CFPE Treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (required at screening visit): Diagnosis of CF confirmed by history of positive chloride sweat test and/or CFTR mutation analysis; History of consistent sputum production on most occasions; FEV1% greater than or equal to 75% of best measurement in previous 6 months; 1 or more hospitalizations for CFPE treatment with intravenous antibiotics within the previous year; Absence of CFPE (i.e., Akron Pulmonary Exacerbation Score <5); Not admitted to hospital within the previous 3 weeks; Body weight greater than or equal to 75% of best measurement in previous 6 months; Provision of signed informed-consent to study protocol; 18<Age>65 Exclusion Criteria: Women who are pregnant or lactating; Subject does not meet Inclusion criteria; Recent and/or persistent visible blood in sputum (hemoptysis); Rescue use of oral antibiotics within the previous 3 weeks, defined as antibiotic use for health deterioration rather than chronic suppression

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Adults - CFPE Treatment<br>Other: CF Pulmonary Exacerbation (CFPE) Treatment | Other: Adults - CFPE Treatment<br>* Hospitalization for comprehensive treatment of CF pulmonary exacerbation, including intravenous (IV) antibiotics, nutritional assessment and support, airway clearance of mucus, use of inhaled mucolytic agents and bronchodilators, glycemic control with insulin, and psychosocial support.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Serum Hepcidin-25 Concentration After Hospitalization for CF Pulmonary Exacerbation (CFPE) Treatment | The primary endpoint of this study is the characterization of 3 groups (i.e., low, intermediate, and high) of serum hepcidin-25 responders to CFPE treatment. Response will be defined as the ratio of post- to pre-treatment serum hepcidin-25 concentration for each subject. | Duration of hospitalization, an expected average of 12 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Percent-Predicted Forced Expiratory Volume in One Second (FEV1%) After Hospitalization for CF Pulmonary Exacerbation (CFPE) Treatment | Post- to pre-treatment ratio for FEV1% for each subject. | Duration of hospitalization, an expected average of 12 days | 
| Change in Body Mass Index (BMI) After Hospitalization for CF Pulmonary Exacerbation (CFPE) Treatment | Post- to pre-treatment ratio for BMI for each subject. | Duration of hospitalization, an expected average of 12 days | 
| Change in CFRSD-CRISS Score After Hospitalization for CF Pulmonary Exacerbation (CFPE) Treatment | CFRSD-CRISS is a patient-reported outcome (PRO) instrument developed by the Seattle Quality of Life Group at the University of Washington and used herein under license to evaluate the severity of symptoms of CF in adults and adolescents (≥12 years) with a chronic respiratory infection. Symptoms assessed in the CFRSD-CRISS are: difficulty breathing, cough, cough up mucus, chest tightness, wheeze, feeling feverish, tired, and chills/sweats. The 8 items quantify symptom severity for the previous 24 hours to capture the magnitude of symptoms in stable CF, during medically treated CF exacerbations, and during recovery from an exacerbation. We will determine the within-subject differences in CFRSD-CRISS score associated with CFPE treatment. | Duration of hospitalization, an expected average of 12 days | 
| Change in Serum Iron After Hospitalization for CF Pulmonary Exacerbation (CFPE) Treatment | Post- to pre-treatment ratio for serum iron concentration for each subject. | Duration of hospitalization, an expected average of 12 days | 
| Change in Serum Interleukin-6 (IL-6) Concentration After Hospitalization for CF Pulmonary Exacerbation (CFPE) Treatment | Post- to pre-treatment ratio for serum interleukin-6 (IL-6) concentration for each subject. | Duration of hospitalization, an expected average of 12 days | 
| Change in Sputum Iron Content After Hospitalization for CF Pulmonary Exacerbation (CFPE) Treatment | Post- to pre-treatment ratio for sputum iron content for each subject. | Duration of hospitalization, an expected average of 12 days | 
| Change in Serum EPO Concentration After Hospitalization for CF Pulmonary Exacerbation (CFPE) Treatment | Post- to pre-treatment ratio for serum erythropoietin (EPO) for each subject. | Duration of hospitalization, an expected average of 12 days | 
| Change in Transferrin Saturation After Hospitalization for CF Pulmonary Exacerbation Treatment | Post- to pre-treatment ratio for transferrin saturation for each subject. | Duration of hospitalization, an expected average of 12 days | 
| Change in Serum TREM-1 Concentration After Hospitalization for CF Pulmonary Exacerbation Treatment | Post- to pre-treatment ratio for serum triggering receptor expressed on myeloid cells-1 (TREM-1) for each subject. | Duration of hospitalization, an expected average of 12 days | 
| Change in Serum sIL-6R Concentration After Hospitalization for CF Pulmonary Exacerbation Treatment | Post- to pre-treatment ratio for serum soluble IL-6 receptor (sIL-6R) concentration for each subject. | Duration of hospitalization, an expected average of 12 days | 
| Change in Hemoglobin Concentration After Hospitalization for CF Pulmonary Exacerbation (CFPE) Treatment | Post- to pre-treatment ratio for serum hemoglobin concentration for each subject. | Duration of hospitalization, an expected average of 12 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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iron, hepcidin-25, pulmonary exacerbation, interleukin-6