Longitudinal Preschool Wheeze Biomarker Study

NCT ID: NCT06237660

Last Updated: 2024-04-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

150 participants

Study Classification

OBSERVATIONAL

Study Start Date

2024-02-01

Study Completion Date

2026-08-31

Brief Summary

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Preschool children (aged 1-5 years) account for 75% of all UK childhood wheezing hospitalisations. This has not changed over 20 years, meaning current treatments are not working and a new approach is needed. Currently, all preschool wheezers are treated with inhaled steroids. However, only about 25% of patients, with allergies, respond well to inhaled steroidsÍž for the other 75%, they are ineffective. This research group has found that some preschool wheezers may have other causes but there are no specific, non-invasive tests to match the right treatment to each child.

The goal of this observational study is to test various bedside tests for this purpose in preschool children with wheeze, to see if they are feasible, accurate and acceptable in this age group.

The research team would like to investigate the following aims:

Aim 1 - To test the proposed panel of simple bedside tests below, to see how accurately they corelate with lower airway infection or inflammation.

Aim 2 - To test the acceptability of these bedside tests are to parents and children, and if they reflect the child's symptoms, symptoms control and medication use.

Aim 3- A small proof-of -concept study, to test if these simple bedside tests, can be used to determine treatment for each individual child.

The panel of simple non-invasive tests that the research team are proposing are:

1. Skin prick tests to common allergies (house dust mite, cat, dog, grass, tree pollen, mixed moulds)
2. Finger prick blood test
3. Phlegm test for bacteria
4. Nose and throat swab for bacteria
5. Lung function test called forced oscillation technique (FOT)

Detailed Description

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Research Question:

Can the research team identify simple bedside tests that can give quick, accurate results while being acceptable to parents and children, and can these tests be successfully used in clinical practice, to decide treatment for preschool wheeze?

Participants will be asked to do these simple tests- skin prick test, finger prick blood test, breathing test, throat swab, and a test to catch their phlegm. The researchers will use two tests to identify children who are likely to respond to inhaled steroids: skin tests for allergies and a finger prick blood test. To identify children with bacterial infections in their lungs, where antibiotics will be useful, the team will obtain a sample of sputum (phlegm) after a salty mist inhalation (saline nebuliser), and will test the accuracy of a throat swab that detects bacteria. The research team will also test how cells called neutrophils work in children without allergies or infection with the same finger prick blood test above. A breathing test called forced oscillation will be used to identify children who may respond to their reliever "blue" inhaler during wheezing attacks.

The research team will also recruit a small number of children, for a trial in which their treatment will be guided by their test result, to see if parents are willing to take part in such a study, before designing a larger trial. This study will be the first to show that new tests can identify different types of preschool wheezing and can be used to plan treatment based on individual children's needs. Researchers will compare to see if children who have their treatment based on the simple bedside tests do better than the children who are just given inhaled steroids.

Conditions

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Wheezing

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Aim 1

To test the proposed panel of simple bedside tests below, to see how accurately they corelate with lower airway infection or inflammation.

The aim is correlate the results from the bronchoscopy with the panel of test proposed, and evaluate if these simple bedside tests can pick up the same level of infection or inflammation and obtain the same results, as the bronchoscopy, which is a much more invasive test, but the only method available at present to get this information.

Bronchoscopy, with bronchoalveolar lavage and endobronchial biopsy

Intervention Type PROCEDURE

These children who will be having a bronchoscopy (a long thin tube, with a camera at the end, which is put inside the lung to look at and collect samples) as part of their standard clinical management, determined by their own consultants or treating physicians. They will be having lung samples (washings from the lung and a tiny piece of tissue taken from the breathing tubes) taken as part of their usual medical management. The research team will ask for consent to use the leftover samples for the bronchoscopy, for the study

Skin prick test

Intervention Type DIAGNOSTIC_TEST

To identify children with allergies. This test will not be done if the child has had allergy testing in the last 6 months

Finger prick blood test

Intervention Type DIAGNOSTIC_TEST

Finger prick testing will be used for blood samples, and it is the same technique used by children with diabetes, to test their blood sugar levels, and therefore is regularly used in this age group successfully. The research team will be obtain the results within minutes, using a point-of-care device. A few more drops of blood, from the same finger prick sample, will be taken to look at how one of the blood cells work, in more detail, in the laboratory. There is no additional finger prick required for this lab test, and the drops of blood will be collected at the same time, from the same prick, as the point of care test.

Forced oscillation technique (FOT)

Intervention Type DIAGNOSTIC_TEST

Breathing test will be performed using forced oscillation technique (FOT), to see how the child's lungs work and to detect airway inflammation. The test will be explained to the child and completed using our established protocols. This test will only require the child to breathe in and out normally, and therefore can be done in preschool aged children. The current test that is used to check lung function called spirometry cannot be used in preschool children, as it involves following complicated instructions. The aim is to assess how well this newer lung function test is tolerated, in children aged 1-5 years.

Sputum induction

Intervention Type PROCEDURE

Sputum induction is a test of obtaining phlegm after inhalation of salt water mist (saline nebuliser) and this will allow the research team to look for any relationships between infection in the lungs and the accuracy of the less invasive, nose and throat swabs. The research team will obtain phlegm samples, with a quick suction after patients have inhaled the salty mist (saline nebuliser) which will help loosen up their phlegm. If the child can cough it up, they will be encouraged to do it.

Oropharyngeal swab

Intervention Type DIAGNOSTIC_TEST

Swabs from children's nose and throats (similar to swab tests that are done for Covid tests), that will be used to test for bacterial infection

Aim 2

The aim is to test how acceptable these bedside tests are to parents and children, and if they reflect the child's symptoms, symptoms control and medication use.

Skin prick test

Intervention Type DIAGNOSTIC_TEST

To identify children with allergies. This test will not be done if the child has had allergy testing in the last 6 months

Finger prick blood test

Intervention Type DIAGNOSTIC_TEST

Finger prick testing will be used for blood samples, and it is the same technique used by children with diabetes, to test their blood sugar levels, and therefore is regularly used in this age group successfully. The research team will be obtain the results within minutes, using a point-of-care device. A few more drops of blood, from the same finger prick sample, will be taken to look at how one of the blood cells work, in more detail, in the laboratory. There is no additional finger prick required for this lab test, and the drops of blood will be collected at the same time, from the same prick, as the point of care test.

Forced oscillation technique (FOT)

Intervention Type DIAGNOSTIC_TEST

Breathing test will be performed using forced oscillation technique (FOT), to see how the child's lungs work and to detect airway inflammation. The test will be explained to the child and completed using our established protocols. This test will only require the child to breathe in and out normally, and therefore can be done in preschool aged children. The current test that is used to check lung function called spirometry cannot be used in preschool children, as it involves following complicated instructions. The aim is to assess how well this newer lung function test is tolerated, in children aged 1-5 years.

Sputum induction

Intervention Type PROCEDURE

Sputum induction is a test of obtaining phlegm after inhalation of salt water mist (saline nebuliser) and this will allow the research team to look for any relationships between infection in the lungs and the accuracy of the less invasive, nose and throat swabs. The research team will obtain phlegm samples, with a quick suction after patients have inhaled the salty mist (saline nebuliser) which will help loosen up their phlegm. If the child can cough it up, they will be encouraged to do it.

Oropharyngeal swab

Intervention Type DIAGNOSTIC_TEST

Swabs from children's nose and throats (similar to swab tests that are done for Covid tests), that will be used to test for bacterial infection

Aim 3

Small proof-of-concept study. This is for a feasibility trial of using the proposed tests and deciding the treatment of their wheeze, based on the results of the tests. Children with evidence of allergen sensitisation +/- blood eosinophilia (\>0.3x109/L) will be prescribed regular inhaled corticosteroids. Children who are non-atopic (non-atopic is defined as blood eosinophil of \<0.3x109/L + no evidence of allergen sensitisation) with positive bacterial detection in sputum, will be prescribed four weeks of targeted antibiotics. Children who are non-atopic with no bacteria detected in sputum, will be prescribed only be prescribed short acting bronchodilators as required. All medications will be prescribed, as per the British National Formulary for Children, based on age and weight.

The aims of this preliminary study are to understand whether parents will agree to be part of such an interventional trial. This will help the research team when designing a future larger clinical trial.

Skin prick test

Intervention Type DIAGNOSTIC_TEST

To identify children with allergies. This test will not be done if the child has had allergy testing in the last 6 months

Finger prick blood test

Intervention Type DIAGNOSTIC_TEST

Finger prick testing will be used for blood samples, and it is the same technique used by children with diabetes, to test their blood sugar levels, and therefore is regularly used in this age group successfully. The research team will be obtain the results within minutes, using a point-of-care device. A few more drops of blood, from the same finger prick sample, will be taken to look at how one of the blood cells work, in more detail, in the laboratory. There is no additional finger prick required for this lab test, and the drops of blood will be collected at the same time, from the same prick, as the point of care test.

Forced oscillation technique (FOT)

Intervention Type DIAGNOSTIC_TEST

Breathing test will be performed using forced oscillation technique (FOT), to see how the child's lungs work and to detect airway inflammation. The test will be explained to the child and completed using our established protocols. This test will only require the child to breathe in and out normally, and therefore can be done in preschool aged children. The current test that is used to check lung function called spirometry cannot be used in preschool children, as it involves following complicated instructions. The aim is to assess how well this newer lung function test is tolerated, in children aged 1-5 years.

Sputum induction

Intervention Type PROCEDURE

Sputum induction is a test of obtaining phlegm after inhalation of salt water mist (saline nebuliser) and this will allow the research team to look for any relationships between infection in the lungs and the accuracy of the less invasive, nose and throat swabs. The research team will obtain phlegm samples, with a quick suction after patients have inhaled the salty mist (saline nebuliser) which will help loosen up their phlegm. If the child can cough it up, they will be encouraged to do it.

Oropharyngeal swab

Intervention Type DIAGNOSTIC_TEST

Swabs from children's nose and throats (similar to swab tests that are done for Covid tests), that will be used to test for bacterial infection

Interventions

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Bronchoscopy, with bronchoalveolar lavage and endobronchial biopsy

These children who will be having a bronchoscopy (a long thin tube, with a camera at the end, which is put inside the lung to look at and collect samples) as part of their standard clinical management, determined by their own consultants or treating physicians. They will be having lung samples (washings from the lung and a tiny piece of tissue taken from the breathing tubes) taken as part of their usual medical management. The research team will ask for consent to use the leftover samples for the bronchoscopy, for the study

Intervention Type PROCEDURE

Skin prick test

To identify children with allergies. This test will not be done if the child has had allergy testing in the last 6 months

Intervention Type DIAGNOSTIC_TEST

Finger prick blood test

Finger prick testing will be used for blood samples, and it is the same technique used by children with diabetes, to test their blood sugar levels, and therefore is regularly used in this age group successfully. The research team will be obtain the results within minutes, using a point-of-care device. A few more drops of blood, from the same finger prick sample, will be taken to look at how one of the blood cells work, in more detail, in the laboratory. There is no additional finger prick required for this lab test, and the drops of blood will be collected at the same time, from the same prick, as the point of care test.

Intervention Type DIAGNOSTIC_TEST

Forced oscillation technique (FOT)

Breathing test will be performed using forced oscillation technique (FOT), to see how the child's lungs work and to detect airway inflammation. The test will be explained to the child and completed using our established protocols. This test will only require the child to breathe in and out normally, and therefore can be done in preschool aged children. The current test that is used to check lung function called spirometry cannot be used in preschool children, as it involves following complicated instructions. The aim is to assess how well this newer lung function test is tolerated, in children aged 1-5 years.

Intervention Type DIAGNOSTIC_TEST

Sputum induction

Sputum induction is a test of obtaining phlegm after inhalation of salt water mist (saline nebuliser) and this will allow the research team to look for any relationships between infection in the lungs and the accuracy of the less invasive, nose and throat swabs. The research team will obtain phlegm samples, with a quick suction after patients have inhaled the salty mist (saline nebuliser) which will help loosen up their phlegm. If the child can cough it up, they will be encouraged to do it.

Intervention Type PROCEDURE

Oropharyngeal swab

Swabs from children's nose and throats (similar to swab tests that are done for Covid tests), that will be used to test for bacterial infection

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

Aim 1, 2 and 3:

* Children aged 1-5 years
* More than 2 hospitalisations for acute wheeze in the last year or
* At least 1 admission requiring high dependency unit or intravenous bronchodilator therapy in the last year.

Aim 1 only:

\- children undergoing clinically indicated bronchoscopy, as determined by their existing medical team, as part of their standard management

Exclusion Criteria

* Alternative respiratory diagnosis such as cystic fibrosis or bronchiectasis.
Minimum Eligible Age

1 Year

Maximum Eligible Age

5 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Action Medical Research

OTHER

Sponsor Role collaborator

Masonic Charitable Foundation

UNKNOWN

Sponsor Role collaborator

Royal Brompton & Harefield NHS Foundation Trust

OTHER

Sponsor Role collaborator

Imperial College London

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sejal Saglani, MD

Role: PRINCIPAL_INVESTIGATOR

Imperial College London

Locations

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Royal Brompton Hospital

London, , United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Cheuk Fung Wong

Role: CONTACT

+4420 7594 9832

Facility Contacts

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Patrik Pettersson

Role: primary

References

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Robinson PFM, Fontanella S, Ananth S, Martin Alonso A, Cook J, Kaya-de Vries D, Polo Silveira L, Gregory L, Lloyd C, Fleming L, Bush A, Custovic A, Saglani S. Recurrent Severe Preschool Wheeze: From Prespecified Diagnostic Labels to Underlying Endotypes. Am J Respir Crit Care Med. 2021 Sep 1;204(5):523-535. doi: 10.1164/rccm.202009-3696OC.

Reference Type BACKGROUND
PMID: 33961755 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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GN3005

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

23IC8468

Identifier Type: -

Identifier Source: org_study_id

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