The BRIDGE Study - Bronchiectasis Research Involving Databases, Genomics and Endotyping

Bronchiectasis Adult Clinical Trial

— BRIDGE  

Official title:

The BRIDGE Study - Bronchiectasis Research Involving Databases, Genomics and Endotyping. An EMBARC2 and EMBARC3 Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03791086
• Other study ID #: 2017RC11
• Status: Recruiting
• Start date: November 1, 2019
• Est. completion date: February 1, 2027

Study information

• Verified date: March 2023
• Source: University of Dundee
• Contact: James D Chalmers, MD, PhD
• Phone: 01382660111
• Email: james.chalmers[@]nhs.scot
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: February 1, 2027
• Est. primary completion date: February 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bronchiectasis
• Bronchiectasis Adult

Locations

Country	Name	City	State
United Kingdom	University of Dundee	Dundee

Sponsors (1)

Lead Sponsor	Collaborator
University of Dundee

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of exacerbations	Worsening of respiratory symptoms as defined by the EMBARC/BRR definition- Eur Respir J. 2017 Jun 8;49(6). pii: 1700051.	up to 3 years
Secondary	Time to first exacerbation	Time to first event after enrolment as defined by the EMBARC/BRR definition- Eur Respir J. 2017 Jun 8;49(6). pii: 1700051.	3 years
Secondary	Quality of life- the quality of life bronchiectasis questionnaire (QOL-B)	Validated questionnaire	3 years
Secondary	Quality of life- the St Georges Respiratory Questionnaire (SGRQ)	Validated questionnaire	3 years
Secondary	Quality of life- The Bronchiectasis impact measure (BIM)	Questionnaire undergoing validation	3 years
Secondary	Quality of life- The Bronchiectasis Health Questionnaire (BHQ)	Validated questionnaire	3 years
Secondary	Forced expiratory volume in 1 second (FEV1)	Spirometry	3 years
Secondary	Severity of disease (the bronchiectasis severity index)	Validated severity assessment tool	3 years
Secondary	Hospitalisation for severe exacerbations	Admission to hospital for an exacerbation meeting the EMBARC/BRR exacerbation definition	3 years
Secondary	All cause mortality	Survival during the study	3 years
Secondary	Infection with Pseudomonas aeruginosa	Defined as isolation in sputum culture or bronchoalveolar lavage meeting the criteria for chronic infection- Ann Am Thorac Soc. 2015 Nov;12(11):1602-11.	3 years
Secondary	Sputum volume	Measured in millilitres per day	3 years