Clinical trial NCT03791086: The BRIDGE Study - Bronchiectasis Research Involving Databases, Genomics and Endotyping
Official title: The BRIDGE Study - Bronchiectasis Research Involving Databases, Genomics and Endotyping. An EMBARC2 and EMBARC3 Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Bronchiectasis Adult
Lead sponsor: University of Dundee
Sponsor class: OTHER
First posted: 2019-01-02
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patients with bronchiectasis

Brief summary: Bronchiectasis is a complex heterogeneous disorder. Treatment is challenging and many recent randomized controlled trials have been negative. It is believed that bronchiectasis as a broad diagnosis incorporates multiple different patient subgroups (also known as phenotypes) and molecular entities (referred to as endotypes). This study aims to phenotype and endotype bronchiectasis during stable disease and exacerbations, to develop strategies for personalised medicine.

Primary Objective To determine molecular endotypes of bronchiectasis which can guide response to treatment.

Secondary Objectives

1. To determine molecular endotypes of stable bronchiectasis
2. To determine the causes and inflammatory profiles of bronchiectasis exacerbations
3. To validate candidate biomarkers of stable and exacerbation endotypes to use in stratified medicine
4. To perform in-vivo or in-vitro proof of concept studies using phenotypic data to identify patient populations likely to benefit in future randomized controlled trials

This is an observational cohort study that will aim to identify patient subgroups and link these with meaningful clinical outcomes.

Detailed description: Background: Bronchiectasis is a common disabling and heterogeneous disease that has been neglected in terms of basic and clinical research. Recent controlled trials have failed to achieve their primary end-points, likely because the optimal patient population to benefit from antibiotic, mucoactive and anti-inflammatory drugs has not been identified. This study aims to explore the clinical, microbiological, inflammatory and functional heterogeneity of the disease with the aim of identifying patient endotypes for stratified medicine.

Study aims and objectives

1. To determine the molecular endotypes of bronchiectasis during stable disease
2. To determine the causes and inflammatory profiles of bronchiectasis exacerbations
3. To validate candidate biomarkers of stable and exacerbation endotypes to use in stratified medicine
4. To perform in-vivo or in-vitro proof of concept studies using phenotypic data to identify patient populations likely to benefit in future randomized controlled trials Study Design: Observational Cohort study

Study methods:

Patients with bronchiectasis will be recruited into an observational study, the objectives of which will be to:

Aim 1 will define and validate endotypes of stable bronchiectasis by studying up to 1000 patients with bronchiectasis. Clinical data, sputum microbiome, sputum proteomics, and systemic and sputum inflammatory marker measurement will be incorporated for analysis. A sub-study (n=200) will be performed using air liquid interface culture of primary airway epithelial cells. Patients will have brushings of the inferior nasal turbinate with assessment of % ciliation, ciliary beat frequency and pattern by high speed video microscopy before and after culture.

Aim 2 will replicate the phenotyping approach to stable patients with 160 patients during exacerbation. This will identify changes from baseline in microbiota, proteomic and other markers associated with onset of exacerbation and allow classification of clusters of exacerbation.

Aim 3, we will externally validate candidate phenotype/endotypes in registered ethically approved external biobanks and aim to demonstrate that validated markers to be linked to potential treatment responses for use in stratified medicine trials.

In total we will recruit 1000 patients for study. These patients will attend the Clinical Research Centre at one of the participating study centres at least once and undergo sampling along with collecting of clinical data. Patients will be asked to consent for their samples to be linked to data held on the EMBARC registry.

Nature of outputs and outcomes/results expected:

This study will aim to establish detailed endotypes in bronchiectasis which can guide response to treatment.

Eligibility criteria: Inclusion Criteria:

* A previous CT scan showing bronchiectasis along with compatible clinical syndrome of cough, sputum production and/or recurrent respiratory tract infections.
* A primary diagnosis of bronchiectasis made by a respiratory physician
* At the screening visit the individual will have been clinically stable for 4 weeks indicated by the lack of any treatment with antibiotics or corticosteroids for a pulmonary exacerbation in the previous 4 weeks.

Exclusion Criteria:

* Inability to give informed consent
* \<18years of age
* Patients with active tuberculosis
* Treatment with antibiotics or corticosteroids for a pulmonary exacerbation in the previous 4 weeks
* Bronchiectasis due to cystic fibrosis

Primary outcomes:
measure: Frequency of exacerbations
timeFrame: up to 3 years
Secondary outcomes:
measure: Time to first exacerbation
timeFrame: 3 years
measure: Quality of life- the quality of life bronchiectasis questionnaire (QOL-B)
timeFrame: 3 years
measure: Quality of life- the St Georges Respiratory Questionnaire (SGRQ)
timeFrame: 3 years
measure: Quality of life- The Bronchiectasis impact measure (BIM)
timeFrame: 3 years
measure: Quality of life- The Bronchiectasis Health Questionnaire (BHQ)
timeFrame: 3 years
measure: Forced expiratory volume in 1 second (FEV1)
timeFrame: 3 years
measure: Severity of disease (the bronchiectasis severity index)
timeFrame: 3 years
measure: Hospitalisation for severe exacerbations
timeFrame: 3 years
measure: All cause mortality
timeFrame: 3 years
measure: Infection with Pseudomonas aeruginosa
timeFrame: 3 years
measure: Sputum volume
timeFrame: 3 years
Other outcomes:
Locations:
city: Dundee
country: United Kingdom
facility: University of Dundee
Study officials:
affiliation: GSK/British Lung Foundation Chair of Respiratory Research
name: James D Chalmers, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: