Observational Trial of the Longitudinal Effects of CFTR Modulator Drugs

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Cystic Fibrosis

• Study Type: Observational
• Enrollment (Anticipated): 80

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

Subjects enrolled in this protocol will be recruited from patients followed by the Adult CF Program at National Jewish Health. The investigators project enrolling 80 subjects with diagnosed CF, 18 years of age or older, with eligible mutations for CFTR modulator therapies. Concomitant use of systemic steroids will be allowed, and typical co-infections or co-morbidities will not result in exclusion.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Jewish Health
• Collaborators: Cystic Fibrosis Foundation

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2019
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: March 20, 2020
• First Submitted That Met QC Criteria: April 16, 2020
• First Posted (Actual): April 20, 2020

Study Record Updates

• Last Update Posted (Actual): September 30, 2022
• Last Update Submitted That Met QC Criteria: September 28, 2022
• Last Verified: September 1, 2022

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: SAAVED19AO-PG

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
• product manufactured in and exported from the U.S.: No