Cystic Fibrosis (CF) Leukocyte Genes as Biomarkers for Novel Therapies

Study Overview
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Brief Summary
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Presently, effectiveness of treatments for CF lung disease is judged by improvement in lung function (FEV1). However, in CF patients, FEV1 can range from severely decreased to normal, and improvements may occur slowly. Thus, clinical trials require many patients over prolonged periods to evaluate medications. As the pace of drug development accelerates, it is no longer possible to test all of the promising candidate therapies using conventional study designs. A sensitive technique for assessing lung inflammation has been developed which uses the expression of genes located in circulating blood cells. Mononuclear cells pass repeatedly through the blood vessels of the lung, and are exposed to many of the inflammatory products that are present in the airways. Over the past 4 years the investigators have identified a small group of candidate genes that are unregulated or downregulated in response to antibiotic treatment. The investigators now propose to prospectively test this method of quantifying lung inflammation in a large group of CF patients undergoing treatment of pulmonary exacerbations. Blood will be sampled before and after antibiotic treatment for a pulmonary exacerbation, and the relative change in gene expression will be compared to improvement in FEV1 and other clinical responses, to determine the utility of this method for use in studies. If successful, this technique could allow for a rapid and noninvasive method to gauge immediate effects by new treatments, and assist caregivers in determining optimal treatment strategies for the individual.

Official Title
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CF Leukocyte Genes as Biomarkers for Novel Therapies

Conditions
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Cystic Fibrosis, Pulmonary Exacerbation

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented diagnosis of CF. Age 18 years old or greater. Presentation at the start of treatment for a pulmonary exacerbation of CF. Ability to perform reproducible Pulmonary Function Tests. Willingness to comply with study procedure and willingness to provide written consent. Exclusion Criteria: Participation in an investigational drug study within one month of enrollment. 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.

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| A<br>CF patients followed by the Adult CF Program at National Jewish Health meeting criteria for an acute pulmonary exacerbation. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Primary analysis is the change in expression of individual and combinations of mononuclear cell genes, obtained pre- and post-antibiotic therapy. |  | 14-21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of changes in PBMC gene expression with changes in FEV1 |  | 14-21 days | 
| Correlation of changes in PBMC gene expression with changes in WBC counts. |  | 14-21 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cystic Fibrosis, pulmonary exacerbation, gene expression, biomarker, inflammation, CF pulmonary exacerbation