TAAI Erasmus Research Initiative to Fight CF: Monitoring Inflammation in CF Lung Disease Into a New Era

NCT05752019 | Completed

• 2 other identifiers: V2.1, 12-08-2022MEC-2021-0907
• Study Type: observational
• Target: 103
• Locations: 1 country
• Sites: 1

Brief Summary

Progressive destruction of the lungs is the main cause of shortened life expectancy in people with cystic fibrosis (pwCF). Inflammation and respiratory infections play a key role in CF lung disease. Previous studies have shown that an increase in inflammatory markers predicts structural lung damage. Close monitoring of pwCF is crucial to adequately provide optimal care. Pulmonary management for pwCF involves treating infections and exacerbations and promoting exercise and mucociliary clearance to slow or prevent structural lung damage. To evaluate the treatment and incite timely interventions it is important for the pulmonary physician to be well-informed about the condition of the lungs. The main monitoring tools in regular CF care are lung function, sputum cultures, symptom reporting and more recently imaging by chest computed tomography (CT-scan) or magnetic resonance imaging (MRI). Strangely enough, there are currently no monitoring tools used in clinics to measure inflammation in the lung, although this is a main factor for progressive lung disease. New highly effective modulator therapy (HEMT) such as elexacaftor/tezacaftor/ivacaftor \[ETI, Kaftrio®\] is transforming CF treatment, vastly improving lung function and reducing exacerbations. Initial CFTR modulators like ivacaftor and lumacaftor/ivacaftor also improved lung function and reduced exacerbations, but studies showed that lung inflammation was still present. The long-term impact of ETI and its effect on inflammation is not yet known. Thus, monitoring pwCF on HEMT may be different from before, as lung damage seen on chest CT will be less apparent and lung function will improve considerably, therefore not being adequate markers for subtle changes in the lungs. Thus, the focus of monitoring in the era of highly effective CFTR modulators needs to change preferably focusing on measuring lung inflammation. An ideal monitoring tool for lung inflammation in pwCF should be non-invasive, efficient, and provide accurate and sensitive results. Currently, sputum and BAL are the most common methods for assessing inflammation, but BAL is invasive and sputum may not always be available. Exhaled breath analysis by the electronic nose (eNose) or gas chromatography-mass spectrometry (GC-MS) of volatile organic compounds (VOCs) shows promise as a non-invasive monitoring tool. Other promising markers and techniques are inflammatory markers in the blood (cytokines and micro-RNA (miRNA)) and urine. Thus, the objective of this project is to design novel, minimally invasive monitoring techniques capable of identifying lung inflammation in pwCF undergoing highly effective CFTR modulator therapy (ETI) compared to those not using CFTR modulators. The efficacy of these innovative techniques will be evaluated and verified against inflammatory markers in sputum, spirometry, and validated symptom and quality of life scores.

Conditions

Cystic Fibrosis; Lung Inflammation; Lung Infection; Lung Disease; Cystic; Lung Diseases; Lung Disease; Cystic, Congenital; Inflammation Lungs; Congenital Disorders; Exacerbation, Symptom; Infections, Bacterial

Keywords

Breathomics; Exhaled Breath Analysis; Biomarkers; elexacaftor/tezacaftor/ivacaftor; Trikafta; Kaftrio; Non-invasive monitoring; Minimal-invasive monitoring; Sputum

Outcome Measures

Primary Outcomes (1)

• Correlation of the peak intensities of Volatile Organic Compounds, measured by GC-MS and eNose, with inflammatory markers in sputum, like IL-8.

  Correlation of Volatile Organic Compounds (VOCs), measured by GC-MS and eNose breath profiles/VOCs, with inflammatory markers in induced sputum (IL-8, free neutrophilic elastase (NE), calprotectin and myeloperoxidase, plus a predetermined cytokine panel). Volatile organic compounds are measured by gas chromatography - mass spectrometry (GC-MS) and eNose. With the GC-MS, Compounds in breath will be identified according to their retention time and m/z ratio. Difference between peak intensities of compounds will be assessed between groups. An untargeted analysis approach will be used to identify compounds that have the most discriminative ability between the defined groups. The sensors in the eNose will change their electric output when a participant breathes through the machine. The change in signal per sensor will be used to correlate with inflammatory markers in sputum and to identify clusters with higher and lower lung inflammation profile.

  Study completion will take an average of 1 year.

Secondary Outcomes (3)

• Correlation of VOCs, measured by GC-MS and eNose, with validated questionnaires

  Study completion will take an average of 1 year.

• Correlation of potential biomarkers in blood and urine with inflammatory markers in sputum, VOCs in Exhaled Breath and validated questionnaires.

  Study completion will take an average of 1 year.

• Change in volatile organic compounds (VOCs), measured by GC-MS, during ETI treatment compared to control group over time.

  Study completion will take an average of 1 year.

Study Arms (4)

ETI treatment group > 12 years

CF patients older than 12, whom are eligible to receive elexacaftor/tezacaftor/ivacaftor treatment.

Control group > 12 years

CF patients older than 12, whom are not eligible to receive any CFTR-modulator.

ETI treatment group < 12 years

CF patients younger than 12, whom are eligible to receive elexacaftor/tezacaftor/ivacaftor treatment.

Control group < 12 years

CF patients younger than 12, whom are not eligible to receive any CFTR-modulator.

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

people with CF older than 6 years of age who are eligible to start on ETI treatment and as a control group people with CF who are not on CFTR modulators.

You may qualify if:

• In order to be eligible to participate in this study, a subject must meet all of the following criteria:
• Diagnosed with CF, either by abnormal sweat test and/or confirmed with 2 CF causing mutations found by genetic analysis, either from heel-prick screening or diagnosed later in life. Aged \>6 years (i.e. children and adults). Age appropriate written informed consent is required.
• In addition, patients need to meet the criteria of one of the following study groups:
• Group 1: Treated group : people with CF with mutations who are eligible to start ETI or who are already using it. This maybe patients who transition from another CFTR modulator or who are CFTR modulator naïve.
• Group 2: Control group: people with CF whom are not eligible to start on any CFTR modulator yet and receive standard treatment. This group will function as controls.

You may not qualify if:

• \- People with CF who cannot follow instructions

Sponsors & Collaborators

• Erasmus Medical Center: lead
• Stichting TAAI: collaborator

Study Sites (1)

Erasmus MC - Sophia Children's Hospital

Rotterdam, South Holland, 3015GD, Netherlands

Location

Related Publications (26)

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Biospecimen

Retention: SAMPLES WITH DNA

For this study we are collecting sputum, blood, exhaled breath and urine. Patients can opt out for each sample, except exhaled breath. These specimens will be collected at each study visit.

MeSH Terms

Conditions

Cystic Fibrosis; Pneumonia; Cystic Disease Of Lung; Lung Diseases; Cystic Adenomatoid Malformation of Lung, Congenital; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Symptom Flare Up; Bacterial Infections

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Respiratory Tract Infections; Infections; Respiratory System Abnormalities; Congenital Abnormalities; Recurrence; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bacterial Infections and Mycoses

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Pediatric pulmonologist

Study Record Dates

• First Submitted: November 15, 2022
• First Posted: March 2, 2023
• Study Start: March 21, 2022
• Primary Completion: November 9, 2023
• Study Completion: December 31, 2024
• Last Updated: July 18, 2025

Record last verified: 2023-09

Locations

NL (1)