Cystic Fibrosis (CF)NCT07892443
Type 2 Inflammation in Adults With Cystic Fibrosis
An observational study of Cystic Fibrosis (CF) and Type 2 Inflammatory Disorders, run by University of Virginia.
Trial summary
The goal of this observational study is to better understand why some adults with cystic fibrosis (CF) continue to have repeated pulmonary exacerbations, or episodes of worsening respiratory symptoms, despite treatment with highly effective CFTR modulator therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cystic Fibrosis (CF), Type 2 Inflammatory Disorders
- How many people
- 100 participants
- Where
- No sites listed yet
- Study dates
- 1 Nov 2026to 31 May 2031
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Adults with cystic fibrosis receiving highly effective CFTR modulator therapy who receive care through the University of Virginia Adult Cystic Fibrosis Program. Participants will be enrolled while clinically stable and followed prospectively for up to approximately 3 years to characterize pulmonary exacerbations and inflammatory phenotypes. After 24 months of prospective observation, participants will be classified according to pulmonary exacerbation frequency for study analyses.
Who may be able to join
- Age 18 years or older
- Diagnosis of cystic fibrosis
- Receiving highly effective CFTR modulator therapy (HEMT) for at least 6 weeks before enrollment
- Clinically stable at the time of enrollment
- Receives cystic fibrosis care through the University of Virginia Adult Cystic Fibrosis Program
- Able and willing to provide informed consent and participate in study procedures
Who cannot join
- Active pulmonary exacerbation at the time of enrollment
- Hospitalization for a pulmonary exacerbation within the 4 weeks before enrollment
- New systemic antibiotic treatment for respiratory symptoms within the 4 weeks before enrollment
- Systemic corticosteroid treatment for respiratory symptoms within the 4 weeks before enrollment
- Pregnancy at the time of enrollment
- Any condition that, in the opinion of the investigator, would make participation in the study unsafe or interfere with completion of study procedures
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
Larry Borish, MD contact
About this study
Official title: Importance of Type 2 Inflammation in Adults With Cystic Fibrosis and Recurrent Pulmonary Exacerbations
The goal of this observational study is to better understand why some adults with cystic fibrosis (CF) continue to have repeated pulmonary exacerbations, or episodes of worsening respiratory symptoms, despite treatment with highly effective CFTR modulator therapy. The study will focus on whether a type of inflammation called type 2 (T2) inflammation may contribute to these pulmonary exacerbations.
The main questions this study aims to answer are:
Read more
Are signs of T2 inflammation more common in adults with CF who have frequent pulmonary exacerbations?
Are there differences in inflammation in the nose and airways between people who have frequent pulmonary exacerbations and those who do not?
How do immune cells and inflammation change during a pulmonary exacerbation?
Participants will:
Allow researchers to collect information about their CF and pulmonary exacerbations from their medical records.
Complete questionnaires about respiratory and sinus symptoms and quality of life.
Provide research blood samples, samples from inside the nose, and exhaled breath condensate.
Be followed for up to approximately 3 years, with additional research samples collected during qualifying pulmonary exacerbations when feasible.
Participants will continue to receive their usual CF medical care. No experimental medications or treatments will be given as part of this study.
Read the detailed description
This prospective observational study will investigate the relationship between type 2 (T2) inflammation and recurrent pulmonary exacerbations in adults with cystic fibrosis (CF) who are receiving highly effective CFTR modulator therapy. Participants will undergo longitudinal clinical follow-up and research biospecimen collection for up to approximately three years.
After at least 24 months of prospective observation, participants will be classified according to their pulmonary exacerbation frequency. Participants averaging two or more qualifying pulmonary exacerbations per year will be classified as having modulator-refractory CF, while those averaging fewer than two qualifying pulmonary exacerbations per year will be classified as having modulator-responsive CF. This classification will be based on prospectively observed exacerbations rather than exacerbation history before enrollment.
The study will evaluate whether participants with modulator-refractory CF demonstrate evidence of persistent T2 inflammation during stable disease. Clinical and blood-based inflammatory characteristics will be assessed, including peripheral blood eosinophils. Airway inflammation will be characterized using nasal epithelial cells and nasal lining fluid, including assessment of gene-expression patterns and soluble inflammatory mediators. Exhaled breath condensate will also be evaluated as an exploratory source of airway inflammatory biomarkers.
For participants who experience qualifying pulmonary exacerbations, additional biospecimens may be collected when feasible without delaying or altering clinically indicated treatment. Paired blood samples collected during stable disease and pulmonary exacerbations will be used to evaluate changes in circulating immune-cell populations, including activated T-helper type 2 (Th2) cells.
The study is observational. Treatment decisions, including treatment of pulmonary exacerbations, will be made by the participant's clinical care team and will not be determined by the research protocol.
- Keywords
- cystic fibrosis, type 2 inflammation
- Medical subject headings
- Cystic Fibrosis
What is being measured
The primary outcome is the main question the study is designed to answer.
Baseline Stable-State Absolute Peripheral Blood Eosinophil Count
Absolute peripheral blood eosinophil count measured during clinical stability at baseline. Eosinophil counts will be compared between participants who, after 36 months of prospective observation, are classified as having modulator-refractory CF (average of ≥2 qualifying pulmonary exacerbations per year) or modulator-responsive CF (average of <2 qualifying pulmonary exacerbations per year).
Measured: Baseline
Secondary outcomes (3)
Change in Nasal Epithelial Gene Expression from Baseline to Pulmonary Exacerbation
Within-participant changes in nasal epithelial gene expression from stable-state baseline to qualifying pulmonary exacerbations will be evaluated using RNA sequencing. Exploratory analyses will characterize changes in gene-expression patterns associated with type 2 inflammation and recurrent pulmonary exacerbations in adults with cystic fibrosis.
Measured: Baseline and qualifying pulmonary exacerbations occurring up to Month 36.
Change in Exhaled Breath Condensate Inflammatory Mediator Concentrations from Baseline to Pulmonary Exacerbation
Within-participant changes in inflammatory mediator concentrations in exhaled breath condensate will be evaluated between stable-state baseline and qualifying pulmonary exacerbations. These analyses will explore noninvasive biomarkers of airway inflammation and their association with changes in clinical state.
Measured: Baseline and qualifying pulmonary exacerbations occurring up to Month 36.
Change in Peripheral Blood Immune Cell Phenotypes from Baseline to Pulmonary Exacerbation
Within-participant changes in peripheral blood immune-cell populations from stable-state baseline to qualifying pulmonary exacerbations will be characterized using high-dimensional flow cytometry. Analyses will emphasize changes in the frequency of CRTH2-positive CD4-positive Th2 effector cells, with exploratory characterization of additional immune-cell populations associated with type 2 inflammation.
Measured: Baseline and qualifying pulmonary exacerbations occurring up to Month 36.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2026
- Study start1 Nov 2026 (estimated)
- Primary completion31 May 2031 (estimated)
- Study completion31 May 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cystic Fibrosis (CF)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Lindsay Somerville, MD, University of Virginia
- Investigators
- Lindsay Somerville, MD, Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07892443
- Sponsor's protocol ID
- HSR303829
- Other IDs
- 1K23HL183757-01
- Status last verified
- Oct 2026
- First submitted
- 22 Sep 2026
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data underlying results reported in publications from this study may be shared, along with relevant supporting documentation, following publication and upon reasonable request. Access will be subject to applicable institutional, IRB, consent, and data-sharing requirements.
Publications
Somerville L, Borish L, Noth I, Albon D. Modulator-refractory cystic fibrosis: Defining the scope and challenges of an emerging at-risk population. Ther Adv Respir Dis. 2024 Jan-Dec;18:17534666241297877. doi: 10.1177/17534666241297877.
PubMed 39543951