Bronchopulmonary DysplasiaINFANCYNCT06342752
The Role of Volatile Organic Compounds (VOCs), Airway Mucins and the Microbiome in the Early Prediction of Bronchopulmonary Dysplasia (BPD)
An observational study of Bronchopulmonary Dysplasia, run by University Hospital, Antwerp at 1 site in Belgium.
Trial summary
Bronchopulmonary dysplasia (BPD), the most common respiratory complication of extremely preterm birth, significantly impacts healthcare with high morbidity and mortality rates. Despite the well-established primordial role of inflammation and oxidative stress in the development of BPD, clinical practice does not… Read more about this study
- Who is it for?
- Ages 0 to 3 daysHealthy volunteers can take part
- Conditions the study is for
- Bronchopulmonary Dysplasia
- What is being tested?
- Breath test, Throat swabs and Placental samples
- How many people
- 140 participants
- Where
- 1 siteBelgium
- Study dates
- 14 Jun 2024to Sep 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 0 to 3 days
- All sexes
- Healthy volunteers accepted
- Child
Study population: Newborn infants born preterm < 30 weeks gestational age at the Antwerp University Hospital and admitted to the neonatal intensive care unit.
Who may be able to join
- Born at a gestational age < 30 weeks
Who cannot join
- Major congenital defect or disorder
- Patients with an unstable general condition as deemed by the attending neonatologist
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Kristien Vanhaverbeke, MD, PhD contact
Belgium1 site, 1 recruiting
- Recruiting
University Hospital Antwerp
Edegem, Antwerp, 2650
Inès Ghys, ines.ghys@uantwerpen.be
About this study
Official title: The Role of Volatile Organic Compounds (VOCs), Airway Mucins and Microbiome in the Development of Bronchopulmonary Dysplasia and the Feasibility of Exhaled Breath VOCs Analysis as an Early Detection Tool
Bronchopulmonary dysplasia (BPD), the most common respiratory complication of extremely preterm birth, significantly impacts healthcare with high morbidity and mortality rates.
Despite the well-established primordial role of inflammation and oxidative stress in the development of BPD, clinical practice does not incorporate the testing for biomarkers associated with the development of BPD. The diagnosis of BPD based on required respiratory support at 36 weeks PML, stresses the need for an early prediction tool which could identify patients with high levels of these biomarkers. This on its turn, could also improve treatment approaches in clinical practice which are currently mostly supportive or non-specific and do not target underlying pathophysiologic pathways.
Read more
Secondly, mucin expression aim to play a rol in other respiratory diseases, whereas in BPD only the potential role of MUC1 was explored.
Thirdly, the composition of the airway microbial composition of an infant is assumed to be influenced by different factors. From early on in pregnancy the airway microbiome of the infant is formed, offering a protective role against pathologies. On the other hand, the role of the airway microbiome in the development of BPD remains unclear and needs to be elucidated.
The threefold aim of this study is as follows:
- The development of a non-invasive breath test that allows early detection of bronchopulmonary dysplasia, using the potential of VOCs in exhaled breath as biomarkers for inflammation and oxidative stress.
II. The exploration of the composition and diversity of the airway microbiome in infants with BPD, their association with exhaled VOCs and the exploration of the placental and vaginal microbiome.
III. The detection of potential alterations in airway mucin expression in BPD patients.
Through this comprehensive approach, we seek to gain a deeper understanding of how these mutual associations may contribute to the later development of BPD.
In total 140 preterm infants, including 70 BPD patients and 70 preterm controls, born below 30 weeks' gestation at the Antwerp University Hospital will be included.
Read the detailed description
After birth, a swab and samples will be collected from the placenta, next to a maternal vaginal swab for microbiome analysis. Breath samples, two oropharyngeal swabs and endotracheal aspirates - in case intubated - will be collected from the infant on different days in the first 28 days of life.
At 36 weeks PMA, BPD is diagnosed if the infant still requires respiratory support. An oxygen reduction test will also be performed to determine if the infant can maintain saturations within a predetermined target range (90-96% in our hospital) during a stepwise reduction of oxygen, while closely monitoring the neonate. At 36 weeks PMA, infants diagnosed with BPD - as well as controls - will undergo a one-time capillary (or venous) blood gas test, which will be mostly done as part of routine care. The blood gas test will be combined with a continuous transcutaneous capnography (tcPCO2) for 24 hours to assess the degree of severity of lung damage, i.e. grade of alveolar hypoventilation by means of hypercapnia.
All enrolled participants, regardless of BPD diagnosis, will have two clinical follow-up study visits after discharge to home, at 6 and at 12 months corrected age. Another oropharyngeal swab will be collected at these visits for microbiome analysis. To assess lung function in all BPD patients, a multiple breath washout test during natural sleep after the administration of melatonin, will be performed at 6 and 12 months corrected age. At 6 and 12 months corrected age, a chest CT will be performed in severe BPD-cases to assess lung structure. Results of follow-up investigations, clinical data, as well as respiratory questionnaires will be used to correlate to findings of the analysis of all samples taken in the NICU. With this approach, it is not only possible to explore if possible biomarkers found in the early weeks of life could predict BPD at 36 weeks PML, but also respiratory/pulmonary outcome at 6 and 12 months corrected age.
- Conditions
- Bronchopulmonary Dysplasia
- Being tested
- Breath test, Throat swabs, Placental samples, Vaginal swab, Endotracheal aspirates
- Keywords
- Volatile Organic Compounds, Preterm birth, Airway microbiome, Airway mucins, Exhaled breath analysis, Placental microbiome, Vaginal microbiome, Early prediction of BPD, Inflammation Lungs, Respiratory morbidity, multiple breath washout test
- Medical subject headings
- Bronchopulmonary Dysplasia, Premature Birth, Pneumonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Breath testDiagnostic test
Also called Exhaled breath analysis, Volatomics, Exhaled Volatile Organic Compounds, Exhaled VOCs
Early detection of volatile organic compounds (VOCs) in breath from preterm infants, collected at several timepoints within the first 4 weeks of life to predict BPD before diagnosis is made at 36 weeks PMA.
Throat swabsOther
A throat swab will be taken on several timepoints within the first 4 weeks of life to detect airway mucin expression. A second throat swab will be taken as proxy for the airway microbiome.
Placental samplesOther
Also called Placental headspace VOCs analysis, Placental swabs
After birth, placental biopsies will be collected for headspace VOCs analysis. A placental swab and a biopsy will be taken for microbiome analysis.
Vaginal swabOther
A vaginal swab will be taken before birth for microbiome analysis.
Endotracheal aspiratesOther
Also called Aspirates
Collection of aspirates, as part of routine care, to detect mucin expression and the lung microbiome.
| Study group | Role | What they receive |
|---|---|---|
| Preterm infants | all included infants will undergo a breath test and two throat swabs, in case the infant is intubated also endotracheal aspirates will be collected Receives: Diagnostic Test: Breath test; Other: Throat swabs; Other: Endotracheal aspirates | |
| Mothers of preterm infants | placental biopsies, a placental swab and a vaginal swab will be taken after birth Receives: Other: Placental samples; Other: Vaginal swab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Exhaled breath Volatile Organic Compounds (VOCs)
Abbundance of VOCs in breath samples to distinguish BPD from preterm controls by means of GC-MS: direct samples in the respiratory circuit as well as indirect samples from air in the incubator
Measured: first 4 weeks of life
Vaginal microbiome
Metagenomic shotgun sequencing after extraction of bacterial DNA from vaginal swabs after birth
Measured: right before delivery
Placental microbiome
Metagenomic shotgun sequencing after extraction of bacterial DNA from samples and subamniotic swabs after birth
Measured: at delivery
Placental headspace VOCs
Abbundance of VOCs in the headspace of placental samples to distinguish BPD from preterm controls
Measured: at delivery
Airway mucin profiles
Genetic expression of airway mucins in BPD and preterm controls on oropharyngeal samples via qRT-PCR
Measured: first 4 weeks of life
Airway microbial profiles
16S RNA sequencing or metagenomic shotgun sequencing after extraction of bacterial DNA from oropharyngeal swabs and aspirates in BPD and preterm controls
Measured: 12 months
Secondary outcomes (5)
Hypercapnia
BPD patients will undergo a blood gas test to assess the degree of lung damage severity
Measured: 3 months
Follow-up structural lung imaging
Chest CT scan in severe BPD cases
Measured: 12 months
Pulmonary function
To determine lung function - as an objective outcome parameter - a multiple breath washout (MBW) test will be performed, all infants with BPD, at the corrected age of 6 and 12 months.
Measured: 12 months
Chronic lung disease outcome 6 months corrected age
Validated respiratory questionnaire will be completed by the parents at 6 months corrected age. The questionnaire at 6 months is based on the Liverpool Respiratory Symptom Questionnaire (LRSQ), a validated tool for evaluating the prevalence of common paediatric respiratory symptoms amongst preschool children. It consists of eight domains, each containing between three and five items. The first six domains assess respiratory symptoms and the remaining two assess the impact of symptoms on the child and family.
Measured: 6 months
Chronic lung disease outcome 12 months corrected age
At 12 months the validated questionnaire 'A parent-completed respiratory questionnaire for 1-year-old children' will be used.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2024
- Study start14 Jun 2024
- Primary completionSep 2026 (estimated)
- Study completionSep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bronchopulmonary DysplasiaStudies of the same condition, open and under way.
- More trials run by University Hospital, AntwerpThe 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
- 140 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Antwerp
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Antonius Mulder, MD, PhD,prof, Principal investigator, University Hospital Antwerp, BelgiumStijn L Verhulst, MD, PhD,prof, Study director, University Hospital Antwerp, Belgium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06342752
- Sponsor's protocol ID
- 6007
- Acronym
- INFANCY
- Status last verified
- Apr 2025
- First submitted
- 13 Mar 2024
- Last updated
- 9 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Volatile Organic Compounds (VOCs), Airway Mucins and Microbiome in the Development of Bronchopulmonary Dysplasia and the Feasibility of Exhaled Breath VOCs Analysis as an Early Detection Tool
- ClinicalTrials.gov ID
- NCT06342752
- Acronym / sponsor ID
- INFANCY / 6007
- Conditions
- Bronchopulmonary Dysplasia
- Keywords
- Volatile Organic Compounds, Preterm birth, Airway microbiome, Airway mucins, Exhaled breath analysis, Placental microbiome, Vaginal microbiome, Early prediction of BPD
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 140 participants (estimated)
- Lead sponsor
- University Hospital, AntwerpUniversity, hospital or other
- Study start
- 14 Jun 2024 (actual)
- Primary completion
- Sep 2026 (estimated)
- Study completion
- Sep 2027 (estimated)
- First posted
- 2 Apr 2024 (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.
Bronchopulmonary dysplasia (BPD), the most common respiratory complication of extremely preterm birth, significantly impacts healthcare with high morbidity and mortality rates.
Despite the well-established primordial role of inflammation and oxidative stress in the development of BPD, clinical practice does not incorporate the testing for biomarkers associated with the development of BPD. The diagnosis of BPD based on required respiratory support at 36 weeks PML, stresses the need for an early prediction tool which could identify patients with high levels of these biomarkers. This on its turn, could also improve treatment approaches in clinical practice which are currently mostly supportive or non-specific and do not target underlying pathophysiologic pathways.
Secondly, mucin expression aim to play a rol in other respiratory diseases, whereas in BPD only the potential role of MUC1 was explored.
Thirdly, the composition of the airway microbial composition of an infant is assumed to be influenced by different factors. From early on in pregnancy the airway microbiome of the infant is formed, offering a protective role against pathologies. On the other hand, the role of the airway microbiome in the development of BPD remains unclear and needs to be elucidated.
The threefold aim of this study is as follows:
- The development of a non-invasive breath test that allows early detection of bronchopulmonary dysplasia, using the potential of VOCs in exhaled breath as biomarkers for inflammation and oxidative stress.
II. The exploration of the composition and diversity of the airway microbiome in infants with BPD, their association with exhaled VOCs and the exploration of the placental and vaginal microbiome.
III. The detection of potential alterations in airway mucin expression in BPD patients.
Through this comprehensive approach, we seek to gain a deeper understanding of how these mutual associations may contribute to the later development of BPD.
In total 140 preterm infants, including 70 BPD patients and 70 preterm controls, born below 30 weeks' gestation at the Antwerp University Hospital will be included.
Detailed description
After birth, a swab and samples will be collected from the placenta, next to a maternal vaginal swab for microbiome analysis. Breath samples, two oropharyngeal swabs and endotracheal aspirates - in case intubated - will be collected from the infant on different days in the first 28 days of life.
At 36 weeks PMA, BPD is diagnosed if the infant still requires respiratory support. An oxygen reduction test will also be performed to determine if the infant can maintain saturations within a predetermined target range (90-96% in our hospital) during a stepwise reduction of oxygen, while closely monitoring the neonate. At 36 weeks PMA, infants diagnosed with BPD - as well as controls - will undergo a one-time capillary (or venous) blood gas test, which will be mostly done as part of routine care. The blood gas test will be combined with a continuous transcutaneous capnography (tcPCO2) for 24 hours to assess the degree of severity of lung damage, i.e. grade of alveolar hypoventilation by means of hypercapnia.
All enrolled participants, regardless of BPD diagnosis, will have two clinical follow-up study visits after discharge to home, at 6 and at 12 months corrected age. Another oropharyngeal swab will be collected at these visits for microbiome analysis. To assess lung function in all BPD patients, a multiple breath washout test during natural sleep after the administration of melatonin, will be performed at 6 and 12 months corrected age. At 6 and 12 months corrected age, a chest CT will be performed in severe BPD-cases to assess lung structure. Results of follow-up investigations, clinical data, as well as respiratory questionnaires will be used to correlate to findings of the analysis of all samples taken in the NICU. With this approach, it is not only possible to explore if possible biomarkers found in the early weeks of life could predict BPD at 36 weeks PML, but also respiratory/pulmonary outcome at 6 and 12 months corrected age.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Preterm infants | – | Diagnostic Test: Breath test, Other: Throat swabs, Other: Endotracheal aspiratesall included infants will undergo a breath test and two throat swabs, in case the infant is intubated also endotracheal aspirates will be collected |
| Mothers of preterm infants | – | Other: Placental samples, Other: Vaginal swabplacental biopsies, a placental swab and a vaginal swab will be taken after birth |
Who may qualify
- Ages
- 0 to 3 days
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- Study population
- Newborn infants born preterm < 30 weeks gestational age at the Antwerp University Hospital and admitted to the neonatal intensive care unit.
Key inclusion criteria (1 listed)
- Born at a gestational age < 30 weeks
Key exclusion criteria (2 listed)
- Major congenital defect or disorder
- Patients with an unstable general condition as deemed by the attending neonatologist
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Breath testAlso: Exhaled breath analysis, Volatomics, Exhaled Volatile Organic Compounds, Exhaled VOCsEarly detection of volatile organic compounds (VOCs) in breath from preterm infants, collected at several timepoints within the first 4 weeks of life to predict BPD before diagnosis is made at 36 weeks PMA. | Diagnostic test | Preterm infants |
| Throat swabsA throat swab will be taken on several timepoints within the first 4 weeks of life to detect airway mucin expression. A second throat swab will be taken as proxy for the airway microbiome. | Other | Preterm infants |
| Placental samplesAlso: Placental headspace VOCs analysis, Placental swabsAfter birth, placental biopsies will be collected for headspace VOCs analysis. A placental swab and a biopsy will be taken for microbiome analysis. | Other | Mothers of preterm infants |
| Vaginal swabA vaginal swab will be taken before birth for microbiome analysis. | Other | Mothers of preterm infants |
| Endotracheal aspiratesAlso: AspiratesCollection of aspirates, as part of routine care, to detect mucin expression and the lung microbiome. | Other | Preterm infants |
Primary outcome
Exhaled breath Volatile Organic Compounds (VOCs)
Time frame: first 4 weeks of life
Abbundance of VOCs in breath samples to distinguish BPD from preterm controls by means of GC-MS: direct samples in the respiratory circuit as well as indirect samples from air in the incubator
Vaginal microbiome
Time frame: right before delivery
Metagenomic shotgun sequencing after extraction of bacterial DNA from vaginal swabs after birth
Placental microbiome
Time frame: at delivery
Metagenomic shotgun sequencing after extraction of bacterial DNA from samples and subamniotic swabs after birth
Placental headspace VOCs
Time frame: at delivery
Abbundance of VOCs in the headspace of placental samples to distinguish BPD from preterm controls
Airway mucin profiles
Time frame: first 4 weeks of life
Genetic expression of airway mucins in BPD and preterm controls on oropharyngeal samples via qRT-PCR
Airway microbial profiles
Time frame: 12 months
16S RNA sequencing or metagenomic shotgun sequencing after extraction of bacterial DNA from oropharyngeal swabs and aspirates in BPD and preterm controls
5 secondary outcomes
Hypercapnia
Time frame: 3 months
Follow-up structural lung imaging
Time frame: 12 months
Pulmonary function
Time frame: 12 months
Chronic lung disease outcome 6 months corrected age
Time frame: 6 months
Chronic lung disease outcome 12 months corrected age
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2025.
- Individual participant dataSharing planned: No
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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.
Kristien Vanhaverbeke, MD, PhD contact
Antonius Mulder, MD, PhD,prof principal investigator
University Hospital Antwerp, Belgium
Stijn L Verhulst, MD, PhD,prof study director
University Hospital Antwerp, Belgium
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 Bronchopulmonary Dysplasia, run by University Hospital, Antwerp at 1 site in Belgium.
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 1 inclusion and 2 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: looking for participants now, as of the sponsor's last update on 9 May 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 Belgium. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Inès Ghys, MD (+3232655230, ines.ghys@uantwerpen.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Exhaled breath Volatile Organic Compounds (VOCs) (time frame: first 4 weeks of life). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 May 2025.