Studying the Airway Microenvironment in Patients Undergoing Surgical and Bronchoscopic Interventions for COPD (COPD-ENVIRON)

September 14, 2021 updated by: Royal Brompton & Harefield NHS Foundation Trust
Studying the airway microenvironment in patients undergoing surgical and bronchoscopic interventions for COPD

Study Overview

Status

Recruiting

Conditions

Detailed Description

Chronic obstructive pulmonary disease (COPD) is an umbrella term encompassing two entities causing progressive and ultimately disabling breathlessness. Emphysema is a process destructive of the airspaces distal to the terminal bronchioles, with loss of gas exchange tissue, of elastic recoil and of circumferential tethering of the small airways leading to their collapse on forced expiration. Chronic bronchitis is a disorder of the bronchi causing excess production and impaired mobilisation of mucus. Increased parasympathetic tone and progressive remodelling of airways impairs response to bronchodilators. Static and dynamic hyperinflation ensue - a persistently expanded chest and flattened diaphragms despite increasing use of accessory respiratory muscles - resulting in a disadvantaged respiratory pump.

Patients with severe emphysema and hyperinflation benefit from lung volume reduction techniques designed to reduce gas trapping and to improve airflow, chest wall and lung mechanics. The best evidence exists for lung volume reduction surgery (LVRS), which however is not without risk and there is increasing interest in the development of bronchoscopic lung volume reduction (BLVR) techniques including emplacement of endobronchial valves and coils and targeted lung denervation (TLD), which have all been shown to improve lung function, exercise capacity, and quality of life.

Endobronchial cryotherapy is a novel investigational treatment in patients with chronic bronchitis. Porcine models have shown ablation of abnormal metaplastic goblet cells and regeneration of healthy ciliated epithelium and submucosa within 48 hours with complete healing by 60 days following treatment. A pilot study evaluated 11 patients undergoing a lobectomy or pneumonectomy for presumed lung cancer. Metered sprays, one to each of two separate locations, were administered 2 weeks prior to surgery, at least 2cm distal to the proposed resection margin (first segmental and lobular bronchi). No adverse events were reported. Histology of the 8 submitted specimens demonstrated localised cryothermic effect extending to but not beyond the submucosa, and minimal inflammation.

Chronic airway infiltration by neutrophils, macrophages, and Th-1 predominant lymphocytes driven by increased expression of inflammatory proteins, cytokines and chemokines, is intensified during exacerbations. It is generally accepted that acute exacerbations accelerate the decline in lung function in COPD. Recent studies have suggested a role for microvesicles (MVs) in the pathogenesis of COPD, driving exacerbations. MVs are fragments of cell membrane ranging from 0.1 to 1µm in diameter shed by almost all eukaryotic cells. They are recognised to be key mediators of intercellular communication, transporting a variety of molecular cargo including proteins and nucleic acids to distant cells, and have been implicated in various inflammatory diseases including COPD. The majority of studies have looked at circulating endothelial-derived MVs, which are elevated in patients with COPD, are significantly higher during an exacerbation, and are predictive of rapid forced expiratory volume in 1 second (FEV1) decline. However, there is a paucity of data on epithelial-derived MVs within the lung. We know from acute lung injury models that alveolar macrophage-derived microvesicles, which carry biologically active tumour necrosis factor, are rapidly released during the early phase and may play a role in initiating the disease process.

Bronchoalveolar lavage and brushings are established techniques to obtain material for respectively, measurement of inflammatory proteins and microvesicles, and for cytology and messenger ribonucleic acid (mRNA) analysis. A novel technique sampling the mucosal lining fluid using a synthetic absorptive matrix ('bronchosorption') has been shown to have greater sensitivity to standard bronchoalveolar lavage (BAL), eliminating the disadvantage of dilution.

A combination of all three techniques to directly harvest lower airway samples at multiples sites of pulmonary inflammation would allow comparison of proteomic, transcriptomic, and histology data from the endobronchial environment before and after intervention. This would be the first study evaluating the lung microenvironment in this context, which may identify predictive biomarkers of response to intervention and future exacerbation risk.

Study Type

Observational

Enrollment (Anticipated)

80

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Chelsea
      • London, Chelsea, United Kingdom, SW3 6NP
        • Recruiting
        • Chelsea & Westminster Hospital
        • Principal Investigator:
          • Masao Takata, Professor
        • Sub-Investigator:
          • Suveer Singh, MBBS PhD
        • Sub-Investigator:
          • Kieran O'Dea, PhD
        • Sub-Investigator:
          • Michael R Wilson, PhD
        • Sub-Investigator:
          • Sanooj Soni, MBBS MRCP
        • Principal Investigator:
          • Pallav L Shah, MBBS FRCP
    • Fulham
      • London, Fulham, United Kingdom, SW3 6NP
        • Not yet recruiting
        • Royal Brompton & Harefields Hospital
        • Contact:
        • Sub-Investigator:
          • Justin Garner, MBBS MRCP

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients with severe COPD who are scheduled to undergo surgical or bronchoscopic lung intervention (n=80)

Description

Inclusion Criteria:

  • Scheduled for lung volume reduction treatment or endobronchial cryotherapy for the management of severe COPD.

Exclusion Criteria:

  • Unwilling or unable to sign the informed consent form
  • Patients with known Category 3 Organisms as per the Advisory Committee on Dangerous Pathogens (ACDP) for example, Tuberculosis or Human Immunodeficiency Virus.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline in airway cytokine levels at 3 months follow-up
Time Frame: Baseline versus 3 months follow-up
Change in airway cytokine levels measured using a multiplex assay, 3 months following interventional treatment
Baseline versus 3 months follow-up

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Association between baseline cytokine levels and future exacerbation frequency at 3 months follow-up
Time Frame: Baseline versus 3 months follow-up
Baseline versus 3 months follow-up
Association between baseline cytokine levels and future decline in lung function at 3 months follow-up
Time Frame: Baseline versus 3 months follow-up
Baseline versus 3 months follow-up
Association between baseline microvesicle levels and future exacerbation frequency at 3 months follow-up
Time Frame: Baseline versus 3 months follow-up
Baseline versus 3 months follow-up
Association between baseline microvesicle levels and future decline in lung function at 3 months follow-up
Time Frame: Baseline versus 3 months follow-up
Baseline versus 3 months follow-up
Change from baseline in airway microvesicle levels at 3 months follow-up
Time Frame: Baseline versus 3 months follow-up
Change in airway microvesicle levels measured using flow cytometry, 3 months following interventional treatment
Baseline versus 3 months follow-up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Royal Brompton & Harefield NHS Foundation Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

February 6, 2017

Primary Completion (ANTICIPATED)

January 1, 2023

Study Completion (ANTICIPATED)

January 1, 2023

Study Registration Dates

First Submitted

December 20, 2016

First Submitted That Met QC Criteria

January 4, 2017

First Posted (ESTIMATE)

January 5, 2017

Study Record Updates

Last Update Posted (ACTUAL)

September 16, 2021

Last Update Submitted That Met QC Criteria

September 14, 2021

Last Verified

September 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 217587

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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