AsthmaNCT06028204
This is a 6-month Observational Study. Patients Included Will be Those Referred With a Possible Diagnosis or an Established Diagnosis of Asthma. It Will Look at the Association of the Asthma Microbiome and Disease Characteristics, Severity and Treatment Response.
An observational study of Asthma, run by Royal College of Surgeons, Ireland.
Trial summary
The goal of this observational study is to investigate the role of the lung microbiome in patients with asthma and how it may influence the response to asthma specific treatments. This will be compared to patients who presented similarly but do not have a diagnosis of asthma. The main aims are to: 1. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Asthma
- What is being tested?
- Biologic Agent
- How many people
- 60 participants
- Where
- No sites listed yet
- Study dates
- Oct 2023to Jul 2025
- 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 18 years and older
- All sexes
- Adult, Older adult
Study population: Patient referred with a possible diagnosis of asthma or established diagnosis of asthma to hospital or the Respiratory Outpatient Department
Who may be able to join
- Patients ≥18 years
- Patients able to give informed consent
- Patients who have been referred with possible asthma or have an established diagnosis of asthma
Who cannot join
- Patients <18 years
- Patients unable to give informed consent
- Patients who are or intend to become pregnant during the study period
- Other co-existent respiratory diagnosis e.g. bronchiectasis, COPD, Pulmonary fibrosis
Trial locations and contacts
No sites are listed yet.
About this study
Official title: The Role of the Lung Microbiome in Asthma and Its Influence on Treatment Response.
The goal of this observational study is to investigate the role of the lung microbiome in patients with asthma and how it may influence the response to asthma specific treatments. This will be compared to patients who presented similarly but do not have a diagnosis of asthma.
The main aims are to:
Read more
- Evaluate the influence of the microbiome on asthma phenotypes
- Evaluate the influence of the microbiome on respiratory physiological change
- Evaluate the effect of asthma treatment on the microbiome and the host response
Participants will be asked to provide a medical history focusing on their asthma and related co-morbidities such as sinus and reflux disease. They will have physiological parameters measured (spirometry, impulse oscillometry, fraction of exhaled nitric oxide). They will have samples collected to assess the upper and lower airway microbiome (oral rinse, nasopharyngeal swab, sputum, exhaled breath condensate and bronchoscopy) as well as the gut microbiome (stool). They will also have serum samples taken to perform host immune profiling (host transcriptome). They will be followed over six months observing how changes to asthma specific treatments, particularly inhaled corticosteroids and biologic agents can affect the microbiome
Read the detailed description
VISIT 1 (Month 0) FACE TO FACE
- Once consented a study ID will be assigned, and basic demographic information taken.
- A standardized medical history will be taken to include target symptom history, exacerbation frequency and hospital admissions.
- A detailed co-morbid history will be taken as will a review of all previous asthma treatments. Validated symptom questionnaires will be completed during the study visits.
- All participants will be given an electronic PEFR monitor.
- Patients on or planned for inhaled therapy will be given an electronic adherence monitor.
- Pulmonary function testing will be performed including Spirometry, Impulse Oscillometry, Fraction of exhaled Nitric Oxide along with bronchodilator reversibility.
- Sample collection will include blood, oral rinse, nasopharyngeal swab, exhaled breath condensate, stool and induced sputum.
- A subset of patients will be consented for bronchoscopy for lower airway sampling.
VISIT 2,3, 4 (Month 1,2, 3) FACE TO FACE
- A detailed history of symptoms will be taken as will a review of all treatment changes.
- Validated symptom questionnaires will be completed during the study visits.
- PEFR and adherence device data from the previous month will be collected and new monitors and devices provided where needed.
- Pulmonary function testing will be performed as above.
- Sample collection will include blood, oral rinse, nasopharyngeal swab, EBC, stool and induced sputum as above.
VISIT 5 (Month 6) FACE TO FACE
- A detailed history of symptoms will be taken as will a review of all treatment changes. - Validated symptom questionnaires will be completed during the study visits.
- PEFR and adherence device data from the previous month will be collected and new monitors and devices provided where needed.
- Pulmonary function testing will be performed as above.
- Sample collection will include blood, oral rinse, nasopharyngeal swab, EBC, stool and induced sputum.
- A subset of patients who had bronchoscopy at VISIT 1 will have bronchoscopy performed again for corresponding sample collection.
PROCEDURES:
Questionnaires:
Validated symptom questionnaires will be completed during the study visits indicated previously. Asthma Control Test measures the adequacy of asthma control and change in asthma control which may occur spontaneously or in response to treatment. The GERD-Q and the SNOT-22 establish the presence and severity of co-morbid Gastro-oesophageal reflux disease and sinus disease, both common asthma co-morbidities, which may affect quality of life, symptom control and treatment response.
Investigations:
Pulmonary function testing will include spirometry, impulse oscillometry (IOS), Peak Expiratory Flow Rate (PEFR) measurement. Fraction of exhaled Nitric Oxide (FeNO), an established biomarker measured routinely in asthma clinics, will also be measured.
Bio-samples:
Background samples will be taken from sampling and storage equipment to examine for environmental contamination including sterile saline, nasopharyngeal swab, oral rinse/sputum pot container and the bronchoscope.
Blood tests will be drawn via phlebotomy and a single needle pass. The total quantity of blood volume drawn will be the minimally acceptable volume used in paediatric patients for research purposes. Maximum total sample volume is 50ml/10 teaspoons.
Oral samples will be collected using a standardized procedure in accordance with the Manual of Procedures for Human Microbiome Project. Study participants will rinse their mouth (swish/gargle) with 15 mL sterile normal saline for 1 min and will expectorate the contents of the mouth into a 50 mL centrifuge tube. Sample should be kept cold on ice until processing.
Nasopharyngeal swab will be collected inserted into each nostril for several seconds.
Induced sputum will be collected in selected patients using hypertonic saline where needed.
EBC will be collected using RTube where a one way breathing valve that allows contaminant free collection of 200 microlitres per minute in adults during normal breathing.
Stool will be collected in a sealable container and stored at -80 for further processing.
Bronchoscopy will be performed under moderate sedation with topical anaesthesia. A small camera is passed through the vocal cords into the upper then lower airways. For a bronchoalveolar lavage (BAL) a total of 60ml of normal saline will be instilled into a pulmonary lobe and the return will be collected for analysis. An endothelial brushing (EB) involves the introduction of a small brush via the bronchoscope to gently brush the airway walls to collect epithelial cells for analysis for morphological and functional studies.
SAMPLE PROCESSING:
Samples will be processed and stored in RCSI. Once all collected, the available samples will be transferred to New York University Hospitals (for our collaborator Dr. Leopoldo Segal), to be processed for microbiome and host transcriptome profiling.
Blood samples will be processed for complete blood count, immunoglobulin E and aeroallergen sensitivity. In addition blood will be processed for host immune profiling.
Background control, oral rinse, nasopharyngeal swab, EBC, induced sputum and stool samples will be processed for microbiome. EBC and induced sputum will also be processed for host immune profiling.
From the bronchoscopy cohort, all collected samples will undergo microbiome analysis. We will also perform host immune profiling on BAL samples. Endobronchial brushes will be processed for host transcriptome analysis.
- Host immune profiling: Cytokine analysis of samples will be done by Luminex multiplex
- 16S rRNA gene sequencing (microbiome): Nucleic acid extraction, 16S rRNA gene amplification, and purification will be performed and sequencing will be performed on a MiSeq platform (Illumina). This data will be analysed with Quantitative Insights Into Microbial Ecology (QIIME).
- Bulk RNAseq (host transciptome): RNAseq will be performed on bronchial epithelial cells obtained by bronchial brushing (EB), using the Hi-seq /Illumina platform. Sequences will be aligned against the hg19 ensemble reference genome, subsequent gene counting will be performed using featureCounts and differential gene expression will be calculated using the DESeq2 package with an adjusted p-value <0.05. Ingenuity Pathway Analysis (IPA) will used to identify top biological functions. Genes will be mapped to Ensembl IDs and subsequently to KEGG pathways. We will also use analytical approaches designed to establish an immunological profiling such as CIBERSORT.
- Conditions
- Asthma
- Being tested
- Biologic Agent
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biologic AgentDrug
Biologic group will have biological agent commenced if considered necessary as part of routine care.
| Study group | Role | What they receive |
|---|---|---|
| Biologic Naïve Group | This will aim to include 50 patients who have been referred with possible asthma or have a diagnosis of asthma, and are established on treatment in the form of bronchodilators and/or inhaled corticosteroids who are not candidates for biologic therapy at present | |
| Biologic Group | This will aim to include 10 patients who have been referred with an established diagnosis of asthma and are on treatment in the form of bronchodilators and/or inhaled corticosteroids and have been selected as suitable candidates for commencing biologic therapy. Receives: Drug: Biologic Agent |
What is being measured
The primary outcome is the main question the study is designed to answer.
Describe microbiome signature across the spectrum of asthma severity
We expect an increasingly dysbiotic signature in the respiratory microbiome of patients with severe asthma.
Measured: 2 years
Establish if there is any association between asthma phenotype and microbiome signature
We expect to see a correlation between dysbiosis in the respiratory microbiome and changes in symptom control and physiological parameters.
Measured: 2 years
Determine whether microbiome signature can predict treatment response or resistence
We expect to identify a microbial signature in the respiratory microbiome associated with treatment response, to both biological therapy as well as inhaled corticosteroids.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2023
- Study startOct 2023 (estimated)
- Primary completionJul 2025 (estimated)
- Study completionJul 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AsthmaStudies 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
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Royal College of Surgeons, Ireland
- Sponsor type
- University, hospital or other
- Collaborators
- The Charitable Infirmary Charitable Trust, New York University
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06028204
- Sponsor's protocol ID
- 23.29
- Status last verified
- Aug 2023
- First submitted
- 31 Aug 2023
- Last updated
- 8 Sep 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: If coded data were to be used again, further patient consent, ethical and data protection approval would be required.
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of the Lung Microbiome in Asthma and Its Influence on Treatment Response.
- ClinicalTrials.gov ID
- NCT06028204
- Acronym / sponsor ID
- 23.29
- Conditions
- Asthma
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Royal College of Surgeons, IrelandUniversity, hospital or other
- Collaborators
- The Charitable Infirmary Charitable Trust, New York University
- Study start
- Oct 2023 (estimated)
- Primary completion
- Jul 2025 (estimated)
- Study completion
- Jul 2025 (estimated)
- First posted
- 8 Sep 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.
The goal of this observational study is to investigate the role of the lung microbiome in patients with asthma and how it may influence the response to asthma specific treatments. This will be compared to patients who presented similarly but do not have a diagnosis of asthma.
The main aims are to:
- Evaluate the influence of the microbiome on asthma phenotypes
- Evaluate the influence of the microbiome on respiratory physiological change
- Evaluate the effect of asthma treatment on the microbiome and the host response
Participants will be asked to provide a medical history focusing on their asthma and related co-morbidities such as sinus and reflux disease. They will have physiological parameters measured (spirometry, impulse oscillometry, fraction of exhaled nitric oxide). They will have samples collected to assess the upper and lower airway microbiome (oral rinse, nasopharyngeal swab, sputum, exhaled breath condensate and bronchoscopy) as well as the gut microbiome (stool). They will also have serum samples taken to perform host immune profiling (host transcriptome). They will be followed over six months observing how changes to asthma specific treatments, particularly inhaled corticosteroids and biologic agents can affect the microbiome
Detailed description
VISIT 1 (Month 0) FACE TO FACE
- Once consented a study ID will be assigned, and basic demographic information taken.
- A standardized medical history will be taken to include target symptom history, exacerbation frequency and hospital admissions.
- A detailed co-morbid history will be taken as will a review of all previous asthma treatments. Validated symptom questionnaires will be completed during the study visits.
- All participants will be given an electronic PEFR monitor.
- Patients on or planned for inhaled therapy will be given an electronic adherence monitor.
- Pulmonary function testing will be performed including Spirometry, Impulse Oscillometry, Fraction of exhaled Nitric Oxide along with bronchodilator reversibility.
- Sample collection will include blood, oral rinse, nasopharyngeal swab, exhaled breath condensate, stool and induced sputum.
- A subset of patients will be consented for bronchoscopy for lower airway sampling.
VISIT 2,3, 4 (Month 1,2, 3) FACE TO FACE
- A detailed history of symptoms will be taken as will a review of all treatment changes.
- Validated symptom questionnaires will be completed during the study visits.
- PEFR and adherence device data from the previous month will be collected and new monitors and devices provided where needed.
- Pulmonary function testing will be performed as above.
- Sample collection will include blood, oral rinse, nasopharyngeal swab, EBC, stool and induced sputum as above.
VISIT 5 (Month 6) FACE TO FACE
- A detailed history of symptoms will be taken as will a review of all treatment changes. - Validated symptom questionnaires will be completed during the study visits.
- PEFR and adherence device data from the previous month will be collected and new monitors and devices provided where needed.
- Pulmonary function testing will be performed as above.
- Sample collection will include blood, oral rinse, nasopharyngeal swab, EBC, stool and induced sputum.
- A subset of patients who had bronchoscopy at VISIT 1 will have bronchoscopy performed again for corresponding sample collection.
PROCEDURES:
Questionnaires:
Validated symptom questionnaires will be completed during the study visits indicated previously. Asthma Control Test measures the adequacy of asthma control and change in asthma control which may occur spontaneously or in response to treatment. The GERD-Q and the SNOT-22 establish the presence and severity of co-morbid Gastro-oesophageal reflux disease and sinus disease, both common asthma co-morbidities, which may affect quality of life, symptom control and treatment response.
Investigations:
Pulmonary function testing will include spirometry, impulse oscillometry (IOS), Peak Expiratory Flow Rate (PEFR) measurement. Fraction of exhaled Nitric Oxide (FeNO), an established biomarker measured routinely in asthma clinics, will also be measured.
Bio-samples:
Background samples will be taken from sampling and storage equipment to examine for environmental contamination including sterile saline, nasopharyngeal swab, oral rinse/sputum pot container and the bronchoscope.
Blood tests will be drawn via phlebotomy and a single needle pass. The total quantity of blood volume drawn will be the minimally acceptable volume used in paediatric patients for research purposes. Maximum total sample volume is 50ml/10 teaspoons.
Oral samples will be collected using a standardized procedure in accordance with the Manual of Procedures for Human Microbiome Project. Study participants will rinse their mouth (swish/gargle) with 15 mL sterile normal saline for 1 min and will expectorate the contents of the mouth into a 50 mL centrifuge tube. Sample should be kept cold on ice until processing.
Nasopharyngeal swab will be collected inserted into each nostril for several seconds.
Induced sputum will be collected in selected patients using hypertonic saline where needed.
EBC will be collected using RTube where a one way breathing valve that allows contaminant free collection of 200 microlitres per minute in adults during normal breathing.
Stool will be collected in a sealable container and stored at -80 for further processing.
Bronchoscopy will be performed under moderate sedation with topical anaesthesia. A small camera is passed through the vocal cords into the upper then lower airways. For a bronchoalveolar lavage (BAL) a total of 60ml of normal saline will be instilled into a pulmonary lobe and the return will be collected for analysis. An endothelial brushing (EB) involves the introduction of a small brush via the bronchoscope to gently brush the airway walls to collect epithelial cells for analysis for morphological and functional studies.
SAMPLE PROCESSING:
Samples will be processed and stored in RCSI. Once all collected, the available samples will be transferred to New York University Hospitals (for our collaborator Dr. Leopoldo Segal), to be processed for microbiome and host transcriptome profiling.
Blood samples will be processed for complete blood count, immunoglobulin E and aeroallergen sensitivity. In addition blood will be processed for host immune profiling.
Background control, oral rinse, nasopharyngeal swab, EBC, induced sputum and stool samples will be processed for microbiome. EBC and induced sputum will also be processed for host immune profiling.
From the bronchoscopy cohort, all collected samples will undergo microbiome analysis. We will also perform host immune profiling on BAL samples. Endobronchial brushes will be processed for host transcriptome analysis.
- Host immune profiling: Cytokine analysis of samples will be done by Luminex multiplex
- 16S rRNA gene sequencing (microbiome): Nucleic acid extraction, 16S rRNA gene amplification, and purification will be performed and sequencing will be performed on a MiSeq platform (Illumina). This data will be analysed with Quantitative Insights Into Microbial Ecology (QIIME).
- Bulk RNAseq (host transciptome): RNAseq will be performed on bronchial epithelial cells obtained by bronchial brushing (EB), using the Hi-seq /Illumina platform. Sequences will be aligned against the hg19 ensemble reference genome, subsequent gene counting will be performed using featureCounts and differential gene expression will be calculated using the DESeq2 package with an adjusted p-value <0.05. Ingenuity Pathway Analysis (IPA) will used to identify top biological functions. Genes will be mapped to Ensembl IDs and subsequently to KEGG pathways. We will also use analytical approaches designed to establish an immunological profiling such as CIBERSORT.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Biologic Naïve Group | – | –This will aim to include 50 patients who have been referred with possible asthma or have a diagnosis of asthma, and are established on treatment in the form of bronchodilators and/or inhaled corticosteroids who are not candidates for biologic therapy at present |
| Biologic Group | – | Drug: Biologic AgentThis will aim to include 10 patients who have been referred with an established diagnosis of asthma and are on treatment in the form of bronchodilators and/or inhaled corticosteroids and have been selected as suitable candidates for commencing biologic therapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Patient referred with a possible diagnosis of asthma or established diagnosis of asthma to hospital or the Respiratory Outpatient Department
Key inclusion criteria (3 listed)
- Patients ≥18 years
- Patients able to give informed consent
- Patients who have been referred with possible asthma or have an established diagnosis of asthma
Key exclusion criteria (4 listed)
- Patients <18 years
- Patients unable to give informed consent
- Patients who are or intend to become pregnant during the study period
- Other co-existent respiratory diagnosis e.g. bronchiectasis, COPD, Pulmonary fibrosis
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 |
|---|---|---|
| Biologic AgentBiologic group will have biological agent commenced if considered necessary as part of routine care. | Drug | Biologic Group |
Primary outcome
Describe microbiome signature across the spectrum of asthma severity
Time frame: 2 years
We expect an increasingly dysbiotic signature in the respiratory microbiome of patients with severe asthma.
Establish if there is any association between asthma phenotype and microbiome signature
Time frame: 2 years
We expect to see a correlation between dysbiosis in the respiratory microbiome and changes in symptom control and physiological parameters.
Determine whether microbiome signature can predict treatment response or resistence
Time frame: 2 years
We expect to identify a microbial signature in the respiratory microbiome associated with treatment response, to both biological therapy as well as inhaled corticosteroids.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2023.
- Individual participant dataSharing planned: Undecided. If coded data were to be used again, further patient consent, ethical and data protection approval would be required.
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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.
Questions about this trial
What is this clinical trial studying?
An observational study of Asthma, run by Royal College of Surgeons, Ireland.
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 3 inclusion and 4 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: status not confirmed, as of the sponsor's last update on 8 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Margaret Gleeson, MB BCh BAO (+353871712690, margaretgleeson@rcsi.ie), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Describe microbiome signature across the spectrum of asthma severity (time frame: 2 years). The study lists 3 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 8 Sep 2023.