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

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ClinicalTrials.gov Identifier: NCT03791086
Recruitment Status : Not yet recruiting
First Posted : January 1, 2019
Last Update Posted : June 14, 2019
Sponsor:
Information provided by (Responsible Party):
University of Dundee

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.


Condition or disease
Bronchiectasis Adult

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.


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Study Type : Observational
Estimated Enrollment : 1000 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: The BRIDGE Study - Bronchiectasis Research Involving Databases, Genomics and Endotyping. An EMBARC2 Study
Estimated Study Start Date : July 1, 2019
Estimated Primary Completion Date : February 1, 2023
Estimated Study Completion Date : January 1, 2024

Group/Cohort
Patients with bronchiectasis
Adult patients with bronchiectasis meeting the inclusion criteria.



Primary Outcome Measures :
  1. Frequency of exacerbations [ Time Frame: up to 3 years ]
    Worsening of respiratory symptoms as defined by the EMBARC/BRR definition- Eur Respir J. 2017 Jun 8;49(6). pii: 1700051.


Secondary Outcome Measures :
  1. Time to first exacerbation [ Time Frame: 3 years ]
    Time to first event after enrolment as defined by the EMBARC/BRR definition- Eur Respir J. 2017 Jun 8;49(6). pii: 1700051.

  2. Quality of life- the quality of life bronchiectasis questionnaire (QOL-B) [ Time Frame: 3 years ]
    Validated questionnaire

  3. Quality of life- the St Georges Respiratory Questionnaire (SGRQ) [ Time Frame: 3 years ]
    Validated questionnaire

  4. Quality of life- The Bronchiectasis impact measure (BIM) [ Time Frame: 3 years ]
    Questionnaire undergoing validation

  5. Quality of life- The Bronchiectasis Health Questionnaire (BHQ) [ Time Frame: 3 years ]
    Validated questionnaire

  6. Forced expiratory volume in 1 second (FEV1) [ Time Frame: 3 years ]
    Spirometry

  7. Severity of disease (the bronchiectasis severity index) [ Time Frame: 3 years ]
    Validated severity assessment tool

  8. Hospitalisation for severe exacerbations [ Time Frame: 3 years ]
    Admission to hospital for an exacerbation meeting the EMBARC/BRR exacerbation definition

  9. All cause mortality [ Time Frame: 3 years ]
    Survival during the study

  10. Infection with Pseudomonas aeruginosa [ Time Frame: 3 years ]
    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.

  11. Sputum volume [ Time Frame: 3 years ]
    Measured in millilitres per day


Biospecimen Retention:   Samples With DNA
Whole blood, DNA Serum Sputum and sputum supernatant Urine Nasal swabs Nasal biopsy


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Adult patients with bronchiectasis
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03791086


Contacts
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Contact: James D Chalmers, MD, PhD 01382660111 jameschalmers1@nhs.net
Contact: Amelia Shoemark, PhD 01382660111 a.shoemark@dundee.ac.uk

Locations
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United Kingdom
University of Dundee Not yet recruiting
Dundee, United Kingdom, DD1 9SY
Contact: James D Chalmers, MD,PhD    01382660111    jameschalmers1@nhs.net   
Contact: Megan Crichton, Msc    01382 383694    m.l.crichton@dundee.ac.uk   
Sponsors and Collaborators
University of Dundee
Investigators
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Principal Investigator: James D Chalmers, MD, PhD GSK/British Lung Foundation Chair of Respiratory Research

Additional Information:
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Responsible Party: University of Dundee
ClinicalTrials.gov Identifier: NCT03791086     History of Changes
Other Study ID Numbers: 2017RC11
First Posted: January 1, 2019    Key Record Dates
Last Update Posted: June 14, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Data from EMBARC supported studies will be made available to researchers. Application for EMBARC data can be made on our website. Further information is available at www.bronchiectasis.eu/dataaccess
Supporting Materials: Study Protocol
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Available following the study subject to approval by the scientific committee as detailed at www.bronchiectasis.eu/dataaccess
Access Criteria: Approval of an analysis protocol by an independent scientific committee
URL: http://www.bronchiectasis.eu/dataaccess

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Bronchiectasis
Bronchial Diseases
Respiratory Tract Diseases