Cystic FibrosisTERRIFIC-MILENCT05752019
TAAI Erasmus Research Initiative to Fight CF: Monitoring Inflammation in CF Lung Disease Into a New Era
An observational study of Cystic Fibrosis and Lung Inflammation, run by Erasmus Medical Center at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 years and older
- Conditions the study is for
- Cystic Fibrosis, Lung Inflammation, Lung Infection
- How many people
- 103 participants
- Where
- 1 siteNetherlands
- Study dates
- 21 Mar 2022to 31 Dec 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
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 6 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- People with CF who cannot follow instructions
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Erasmus MC - Sophia Children's Hospital
Rotterdam, South Holland, 3015GD
About this study
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.
Read more
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.
Read the detailed description
Objective:
The overall aim of the study is to develop innovative minimally invasive monitoring techniques that can identify lung inflammation in pwCF when using highly effective modulators, compared to patients whom are not eligible for CFTR modulators (control group) yet.
Primary objective is to assess whether measuring VOCs with GC-MS is a sensitive method to monitor changes in lung inflammation in pwCF.
Secondary objectives are:
- To assess whether eNose is a sensitive method to monitor changes in lung inflammation in pwCF.
- To explore the usefulness of other inflammatory markers in blood and urine.
Study design: Explorative cohort study aimed to develop innovative minimally invasive monitoring techniques that can identify lung inflammation in pwCF when using highly effective CFTR modulators. (eNose, GC-MS, inflammatory markers in urine and blood), compared to a control group: pwCF not using CFTR modulators. Furthermore, the investigators will compare these techniques with inflammatory markers in induced sputum, conventional spirometry, symptom and quality of life scores.
Study population: pwCF older than 6 years of age who are eligible to start on ETI treatment and as a control group pwCF who are not on CFTR modulators,
Intervention: Subjects will be included till at least 3 study visits have taken place during treatment with ETI or for the control group: 3 consecutive regular outpatient clinic visits, which are usually 3 months apart. If the subject has not started with ETI an extra visit at baseline will be added just before start of ETI. At the study visits routine care checks will be done, such as spirometry and blood sampling for liver enzyme monitoring. The extra investigations performed at these study visits are: exhaled breath sampling, 3 extra vials of blood, urine collection, induced sputum. Lung clearance index (LCI) will be done for subjects below 18 years of age. Subjects may opt out for blood, induced sputum and urine samples, there always need to be an exhaled breath sampling with eNose and GC-MS. If the patient has a contra-indication or does not want to participate in the induced sputum procedure, the investigators will attempt to collect spontaneous expectorated sputum instead.
To limit their burden of the study for the age group 6-11, the investigators will not conduct all measurements in that age group. Resulting, in the following difference in study design between two age groups:
Patients >12 years: At all visits there will be exhaled breath sampling, 3 extra vials of blood with a blooddraw, induced sputum, urine sample and 2 questionnaires (QoL and symptom score).
Patients <12 years: At all visits there will be exhaled breath sampling and 1 questionnaire (symptom score) will be done by doing an interview with the child. On the last visit 2 extra vials of blood will be collected. For patients 6-18 years of age a multiple breath washout (MBW) for LCI will be scheduled at study visits.
Main study parameters/endpoints:
Primary endpoint is the comparison of VOCs, measured by GC-MS, during ETI treatment compared to control group over time during 3 different study visits.
Secondary endpoints entail the correlation of VOCs by GC-MS breath profiles/VOCs, measured by eNose, inflammatory markers in induced sputum (IL-8, free neutrophilic elastase (NE), calprotectin and myeloperoxidase, plus a predetermined cytokine panel), blood (IL-18, IL-1β, TNF, hsCRP, sCD14, calprotectin, HGMB-1, amyloid and miRNA), urine and, lung function, quality of life and symptom scores at baseline (if available) and overtime during 3 consecutive study visits. In addition, the change of VOCs by GC-MS and eNose from baseline till 3 months of ETI treatment will be investigated.
- Conditions
- Cystic Fibrosis, Lung Inflammation, Lung Infection, Lung Disease; Cystic, Lung Diseases, Lung Disease; Cystic, Congenital
- Keywords
- Breathomics, Exhaled Breath Analysis, Biomarkers, elexacaftor/tezacaftor/ivacaftor, Trikafta, Kaftrio, Non-invasive monitoring, Minimal-invasive monitoring, Sputum
- Medical subject headings
- 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
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Study completion will take an average of 1 year.
Secondary outcomes (3)
Correlation of VOCs, measured by GC-MS and eNose, with validated questionnaires
Correlation of VOCs by GC-MS and eNose breath profiles/VOCs with validated questionnaires (CFRSD-CRISS \& CFQ-R). CFRSD-CRISS is symptom score questionnaire and the CFQ-R a quality of life questionnaire. Both questionnaires result in certain scores, which will be used for the analysis and validation of the breath analyzing techniques. Volatile organic compounds are analyzed with GC-MS and eNose as described at the primary outcome.
Measured: 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.
The targeted biomarkers are listed in the study description.
Measured: 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.
Volatile organic compounds are measured by gas chromatography - mass spectrometry. 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. A untargeted analysis approach will be used to identify compounds that have the most discriminative ability between the defined groups.
Measured: Study completion will take an average of 1 year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2023
- Study start21 Mar 2022
- Primary completion9 Nov 2023
- Study completion31 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (26)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by Erasmus Medical CenterThe sponsor's other registered studies.
- 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
- 103 participants (actual)
Sponsor and investigators
- Lead sponsor
- Erasmus Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Stichting TAAI
- Responsible party
- Principal investigator, Hettie M Janssens, MD PhD, Erasmus Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05752019
- Sponsor's protocol ID
- V2.1, 12-08-2022
- Other IDs
- MEC-2021-0907
- Acronym
- TERRIFIC-MILE
- Status last verified
- Sep 2023
- First submitted
- 15 Nov 2022
- Last updated
- 18 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
De Boeck K. Cystic fibrosis in the year 2020: A disease with a new face. Acta Paediatr. 2020 May;109(5):893-899. doi: 10.1111/apa.15155. Epub 2020 Jan 22.
PubMed 31899933Horati H, Janssens HM, Margaroli C, Veltman M, Stolarczyk M, Kilgore MB, Chou J, Peng L, Tiddens HAMW, Chandler JD, Tirouvanziam R, Scholte BJ. Airway profile of bioactive lipids predicts early progression of lung disease in cystic fibrosis. J Cyst Fibros. 2020 Nov;19(6):902-909. doi: 10.1016/j.jcf.2020.01.010. Epub 2020 Feb 10.
PubMed 32057679Sly PD, Gangell CL, Chen L, Ware RS, Ranganathan S, Mott LS, Murray CP, Stick SM; AREST CF Investigators. Risk factors for bronchiectasis in children with cystic fibrosis. N Engl J Med. 2013 May 23;368(21):1963-70. doi: 10.1056/NEJMoa1301725.
PubMed 23692169Wijker NE, Vidmar S, Grimwood K, Sly PD, Byrnes CA, Carlin JB, Cooper PJ, Robertson CF, Massie RJ, Kemner van de Corput MPC, Cheney J, Tiddens HAWM, Wainwright CE; Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) and Follow-up of the ACFBAL (CF-FAB) study groups; following investigators constitute the ACFBAL Study Investigators Group:; following investigators constitute the CF FAB Study Investigators Group:; Additional contributions: We are indebted to all current and former clinical and research staff from Queensland Children's Hospital, Brisbane:. Early markers of cystic fibrosis structural lung disease: follow-up of the ACFBAL cohort. Eur Respir J. 2020 Apr 3;55(4):1901694. doi: 10.1183/13993003.01694-2019. Print 2020 Apr.
PubMed 31949117Smyth AR, Bell SC, Bojcin S, Bryon M, Duff A, Flume P, Kashirskaya N, Munck A, Ratjen F, Schwarzenberg SJ, Sermet-Gaudelus I, Southern KW, Taccetti G, Ullrich G, Wolfe S; European Cystic Fibrosis Society. European Cystic Fibrosis Society Standards of Care: Best Practice guidelines. J Cyst Fibros. 2014 May;13 Suppl 1:S23-42. doi: 10.1016/j.jcf.2014.03.010.
PubMed 24856775Margaroli C, Garratt LW, Horati H, Dittrich AS, Rosenow T, Montgomery ST, Frey DL, Brown MR, Schultz C, Guglani L, Kicic A, Peng L, Scholte BJ, Mall MA, Janssens HM, Stick SM, Tirouvanziam R. Elastase Exocytosis by Airway Neutrophils Is Associated with Early Lung Damage in Children with Cystic Fibrosis. Am J Respir Crit Care Med. 2019 Apr 1;199(7):873-881. doi: 10.1164/rccm.201803-0442OC.
PubMed 30281324Heijerman HGM, McKone EF, Downey DG, Van Braeckel E, Rowe SM, Tullis E, Mall MA, Welter JJ, Ramsey BW, McKee CM, Marigowda G, Moskowitz SM, Waltz D, Sosnay PR, Simard C, Ahluwalia N, Xuan F, Zhang Y, Taylor-Cousar JL, McCoy KS; VX17-445-103 Trial Group. Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial. Lancet. 2019 Nov 23;394(10212):1940-1948. doi: 10.1016/S0140-6736(19)32597-8. Epub 2019 Oct 31.
PubMed 31679946Middleton PG, Mall MA, Drevinek P, Lands LC, McKone EF, Polineni D, Ramsey BW, Taylor-Cousar JL, Tullis E, Vermeulen F, Marigowda G, McKee CM, Moskowitz SM, Nair N, Savage J, Simard C, Tian S, Waltz D, Xuan F, Rowe SM, Jain R; VX17-445-102 Study Group. Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele. N Engl J Med. 2019 Nov 7;381(19):1809-1819. doi: 10.1056/NEJMoa1908639. Epub 2019 Oct 31.
PubMed 31697873Jarosz-Griffiths HH, Scambler T, Wong CH, Lara-Reyna S, Holbrook J, Martinon F, Savic S, Whitaker P, Etherington C, Spoletini G, Clifton I, Mehta A, McDermott MF, Peckham D. Different CFTR modulator combinations downregulate inflammation differently in cystic fibrosis. Elife. 2020 Mar 2;9:e54556. doi: 10.7554/eLife.54556.
PubMed 32118580Fens N, van der Schee MP, Brinkman P, Sterk PJ. Exhaled breath analysis by electronic nose in airways disease. Established issues and key questions. Clin Exp Allergy. 2013 Jul;43(7):705-15. doi: 10.1111/cea.12052.
PubMed 23786277de Vries R, Dagelet YWF, Spoor P, Snoey E, Jak PMC, Brinkman P, Dijkers E, Bootsma SK, Elskamp F, de Jongh FHC, Haarman EG, In 't Veen JCCM, Maitland-van der Zee AH, Sterk PJ. Clinical and inflammatory phenotyping by breathomics in chronic airway diseases irrespective of the diagnostic label. Eur Respir J. 2018 Jan 11;51(1):1701817. doi: 10.1183/13993003.01817-2017. Print 2018 Jan.
PubMed 29326334Sagel SD, Kapsner RK, Osberg I. Induced sputum matrix metalloproteinase-9 correlates with lung function and airway inflammation in children with cystic fibrosis. Pediatr Pulmonol. 2005 Mar;39(3):224-32. doi: 10.1002/ppul.20165.
PubMed 15635615Thomassen JC, Trojan T, Walz M, Vohlen C, Fink G, Rietschel E, Alejandre Alcazar MA, van Koningsbruggen-Rietschel S. Reduced neutrophil elastase inhibitor elafin and elevated transforming growth factor-beta1 are linked to inflammatory response in sputum of cystic fibrosis patients with Pseudomonas aeruginosa. ERJ Open Res. 2021 Jul 19;7(3):00636-2020. doi: 10.1183/23120541.00636-2020. eCollection 2021 Jul.
PubMed 34291109Jain R, Baines A, Khan U, Wagner BD, Sagel SD. Evaluation of airway and circulating inflammatory biomarkers for cystic fibrosis drug development. J Cyst Fibros. 2021 Jan;20(1):50-56. doi: 10.1016/j.jcf.2020.06.017. Epub 2020 Jul 1.
PubMed 32622665Quon BS, Ngan DA, Wilcox PG, Man SF, Sin DD. Plasma sCD14 as a biomarker to predict pulmonary exacerbations in cystic fibrosis. PLoS One. 2014 Feb 20;9(2):e89341. doi: 10.1371/journal.pone.0089341. eCollection 2014.
PubMed 24586701
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- TAAI Erasmus Research Initiative to Fight CF: Monitoring Inflammation in CF Lung Disease Into a New Era
- ClinicalTrials.gov ID
- NCT05752019
- Acronym / sponsor ID
- TERRIFIC-MILE / V2.1, 12-08-2022
- Conditions
- Cystic Fibrosis, Lung Inflammation, Lung Infection, Lung Disease; Cystic, Lung Diseases, Lung Disease; Cystic, Congenital
- Keywords
- Breathomics, Exhaled Breath Analysis, Biomarkers, elexacaftor/tezacaftor/ivacaftor, Trikafta, Kaftrio, Non-invasive monitoring, Minimal-invasive monitoring
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 103 participants (actual)
- Lead sponsor
- Erasmus Medical CenterUniversity, hospital or other
- Collaborators
- Stichting TAAI
- Study start
- 21 Mar 2022 (actual)
- Primary completion
- 9 Nov 2023 (actual)
- Study completion
- 31 Dec 2024 (actual)
- First posted
- 2 Mar 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Objective:
The overall aim of the study is to develop innovative minimally invasive monitoring techniques that can identify lung inflammation in pwCF when using highly effective modulators, compared to patients whom are not eligible for CFTR modulators (control group) yet.
Primary objective is to assess whether measuring VOCs with GC-MS is a sensitive method to monitor changes in lung inflammation in pwCF.
Secondary objectives are:
- To assess whether eNose is a sensitive method to monitor changes in lung inflammation in pwCF.
- To explore the usefulness of other inflammatory markers in blood and urine.
Study design: Explorative cohort study aimed to develop innovative minimally invasive monitoring techniques that can identify lung inflammation in pwCF when using highly effective CFTR modulators. (eNose, GC-MS, inflammatory markers in urine and blood), compared to a control group: pwCF not using CFTR modulators. Furthermore, the investigators will compare these techniques with inflammatory markers in induced sputum, conventional spirometry, symptom and quality of life scores.
Study population: pwCF older than 6 years of age who are eligible to start on ETI treatment and as a control group pwCF who are not on CFTR modulators,
Intervention: Subjects will be included till at least 3 study visits have taken place during treatment with ETI or for the control group: 3 consecutive regular outpatient clinic visits, which are usually 3 months apart. If the subject has not started with ETI an extra visit at baseline will be added just before start of ETI. At the study visits routine care checks will be done, such as spirometry and blood sampling for liver enzyme monitoring. The extra investigations performed at these study visits are: exhaled breath sampling, 3 extra vials of blood, urine collection, induced sputum. Lung clearance index (LCI) will be done for subjects below 18 years of age. Subjects may opt out for blood, induced sputum and urine samples, there always need to be an exhaled breath sampling with eNose and GC-MS. If the patient has a contra-indication or does not want to participate in the induced sputum procedure, the investigators will attempt to collect spontaneous expectorated sputum instead.
To limit their burden of the study for the age group 6-11, the investigators will not conduct all measurements in that age group. Resulting, in the following difference in study design between two age groups:
Patients >12 years: At all visits there will be exhaled breath sampling, 3 extra vials of blood with a blooddraw, induced sputum, urine sample and 2 questionnaires (QoL and symptom score).
Patients <12 years: At all visits there will be exhaled breath sampling and 1 questionnaire (symptom score) will be done by doing an interview with the child. On the last visit 2 extra vials of blood will be collected. For patients 6-18 years of age a multiple breath washout (MBW) for LCI will be scheduled at study visits.
Main study parameters/endpoints:
Primary endpoint is the comparison of VOCs, measured by GC-MS, during ETI treatment compared to control group over time during 3 different study visits.
Secondary endpoints entail the correlation of VOCs by GC-MS breath profiles/VOCs, measured by eNose, inflammatory markers in induced sputum (IL-8, free neutrophilic elastase (NE), calprotectin and myeloperoxidase, plus a predetermined cytokine panel), blood (IL-18, IL-1β, TNF, hsCRP, sCD14, calprotectin, HGMB-1, amyloid and miRNA), urine and, lung function, quality of life and symptom scores at baseline (if available) and overtime during 3 consecutive study visits. In addition, the change of VOCs by GC-MS and eNose from baseline till 3 months of ETI treatment will be investigated.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- 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.
Key inclusion criteria (5 listed)
- 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.
- 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.
Key exclusion criteria (1 listed)
- People with CF who cannot follow instructions
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Correlation of the peak intensities of Volatile Organic Compounds, measured by GC-MS and eNose, with inflammatory markers in sputum, like IL-8.
Time frame: Study completion will take an average of 1 year.
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.
3 secondary outcomes
Correlation of VOCs, measured by GC-MS and eNose, with validated questionnaires
Time frame: 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.
Time frame: 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.
Time frame: Study completion will take an average of 1 year.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2025.
- Background: PubMed 31899933De Boeck K. Cystic fibrosis in the year 2020: A disease with a new face. Acta Paediatr. 2020 May;109(5):893-899. doi: 10.1111/apa.15155. Epub 2020 Jan 22.
- Background: PubMed 32057679Horati H, Janssens HM, Margaroli C, Veltman M, Stolarczyk M, Kilgore MB, Chou J, Peng L, Tiddens HAMW, Chandler JD, Tirouvanziam R, Scholte BJ. Airway profile of bioactive lipids predicts early progression of lung disease in cystic fibrosis. J Cyst Fibros. 2020 Nov;19(6):902-909. doi: 10.1016/j.jcf.2020.01.010. Epub 2020 Feb 10.
- Background: PubMed 23692169Sly PD, Gangell CL, Chen L, Ware RS, Ranganathan S, Mott LS, Murray CP, Stick SM; AREST CF Investigators. Risk factors for bronchiectasis in children with cystic fibrosis. N Engl J Med. 2013 May 23;368(21):1963-70. doi: 10.1056/NEJMoa1301725.
- Background: PubMed 31949117Wijker NE, Vidmar S, Grimwood K, Sly PD, Byrnes CA, Carlin JB, Cooper PJ, Robertson CF, Massie RJ, Kemner van de Corput MPC, Cheney J, Tiddens HAWM, Wainwright CE; Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) and Follow-up of the ACFBAL (CF-FAB) study groups; following investigators constitute the ACFBAL Study Investigators Group:; following investigators constitute the CF FAB Study Investigators Group:; Additional contributions: We are indebted to all current and former clinical and research staff from Queensland Children's Hospital, Brisbane:. Early markers of cystic fibrosis structural lung disease: follow-up of the ACFBAL cohort. Eur Respir J. 2020 Apr 3;55(4):1901694. doi: 10.1183/13993003.01694-2019. Print 2020 Apr.
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- Background: PubMed 30281324Margaroli C, Garratt LW, Horati H, Dittrich AS, Rosenow T, Montgomery ST, Frey DL, Brown MR, Schultz C, Guglani L, Kicic A, Peng L, Scholte BJ, Mall MA, Janssens HM, Stick SM, Tirouvanziam R. Elastase Exocytosis by Airway Neutrophils Is Associated with Early Lung Damage in Children with Cystic Fibrosis. Am J Respir Crit Care Med. 2019 Apr 1;199(7):873-881. doi: 10.1164/rccm.201803-0442OC.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cystic Fibrosis and Lung Inflammation, run by Erasmus Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Correlation of the peak intensities of Volatile Organic Compounds, measured by GC-MS and eNose, with inflammatory markers in sputum, like IL-8. (time frame: Study completion will take an average of 1 year.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05752019, which also lists 26 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jul 2025.