Observational Trial of the Longitudinal Effects of CFTR Modulator Drugs

Study Overview
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Brief Summary
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CF patients enrolled in this protocol will be recruited from patients followed by the Adult CF Program at National Jewish Health. Patients will be selected based on planned use of a CFTR modulator by their primary physician. No patient will be started on (or will switch) CFTR modulator agents for the purpose of the study. After enrollment, biological samples may be collected at two different time points prior to treatment initiation. One set of samples will be collected at baseline health prior to CFTR modulator initiation or change. A second set of samples will be obtained in subjects at the time of acute pulmonary exacerbation, if one occurs prior to CFTR modulator initiation or change. Post CFTR modulator initiation study assessments will be obtained at least one month after starting treatment and continue up to 2 times a year (including during pulmonary exacerbations), in order to document longitudinal effects of therapies and changes in inflammatory biology over time. At the time of each biological sampling, blood, sputum sample, urine, and a quality of life assessment will be acquired in all enrolled subjects. In addition to demographic data, clinical data, such as quantitative microbiology and simple spirometry will be recorded at the time of sample collection.

Official Title
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The Natural History of Cystic Fibrosis in the Era of Next Gen Combination Modulator Agents: Novel Treatment Targets in an Evolving Disease

Conditions
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Cystic Fibrosis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented diagnosis of CF with an eligible mutation for modulator treatment. Age 18 years old or older. Patient is starting a CFTR modulator as part of their clinical care or switching CFTR modulator therapy agents, pending FDA approval. Ability to perform reproducible Pulmonary Function Tests. Willingness to comply with study procedure and willingness to provide written consent. 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.

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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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in blood inflammatory markers | Changes in host inflammation as measured in peripheral blood memory T cells | Before initiation/change of CFTR modulator and after, on average 6 months apart | 
| Change in sputum microbiology | Changes in the bacterial burden in sputum as measured by bacterial RNA | Before initiation/change of CFTR modulator and after, on average 6 months apart | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in lung function | Changes in lung function as measured by FEV1, % predicted | Before initiation/change of CFTR modulator and after, on average 6 months apart | 
| Changes in urine inflammatory marker | Changes in host inflammation as measured by urinary neutrophil gelatinase-associated lipocalin (NGAL) | Before initiation/change of CFTR modulator and after, on average 6 months apart | 
| Changes in quality of life | Changes in quality of life as measured by Cystic Fibrosis Questionnaire - Revised (CFQ-R) | Before initiation/change of CFTR modulator and after, on average 6 months apart | 
| Changes in hospitalizations | Changes in frequency/number of hospitalizations for treatment of pulmonary exacerbation | Before initiation/change of CFTR modulator and after, on average 6 months apart |