Tissue Engineering Approaches to Treat COPD

NCT04878445 | Active Not Recruiting

• 1 other identifier: 1517
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The study is a pilot/laboratory study comparing lung tissue from control participants with tissue from COPD participants with a chronic bronchitis or emphysema phenotypes. Tissue will be characterised mechanically and biochemically. Lung cells, including DASCp63/Krt5 with a possible role in disease pathology, will be isolated, expanded in vitro, characterised, and banked. Biomaterials will be selected and tested with regards to mechanical and physical properties and selected for use in the production of TELEs with properties matched to healthy and diseased lung tissue. The resulting TELEs will be tested in an ex vivo tissue culture model to determine the extent of their integration with lung.

Conditions

Lung Cancer

Outcome Measures

Primary Outcomes (1)

• The overall aim of this project is to produce in vitro tissue engineered lung equivalents (TELEs) seeded with cells obtained from:

  P1) The determination of the scale-up suitability of in vitro lung equivalents, their mechanical properties, and in vitro degradation rates. P2) Development of in vitro DASCp63/Krt5 culture models to support re-establishment of local lung architecture. P3) Establishment of ex vivo lung culture models to support the lung tissue equivalents' evaluation.

  Through study completion upto 1 year

Secondary Outcomes (1)

• To achieve an understanding of the mechanical properties of diseased and healthy lung tissue.

  Through study completion, upto 1 year

Study Arms (3)

Cohort A: 10 participants with no COPD

Control patients Have no physician diagnosis of COPD Have no other significant chronic lung disease (asthma, fibrotic diseases) or ongoing lung infection other than the suspected cancer for which they have been referred for surgery. Lifelong never-smokers or ex-smokers (\< 10 pack years). (1 pack year= 20 cigarettes/day for 1 year).

Procedure: Patients undergoing standard surgery, excess tissue only will be analysed with patient consent.

Cohort B: 10 participants with COPD - chronic bronchitis

Have a physician diagnosis of COPD with primarily a chronic bronchitis presentation (determined via CT, spirometry, histopathology, GOLD COPD classification).

Procedure: Patients undergoing standard surgery, excess tissue only will be analysed with patient consent.

Cohort C: 10 participants with COPD emphysema

Have a physician diagnosis of COPD with primarily a emphysema presentation (determined via CT, spirometry, histopathology, GOLD COPD classification) .

Procedure: Patients undergoing standard surgery, excess tissue only will be analysed with patient consent.

Interventions

Patients undergoing standard surgery, excess tissue only will be analysed with patient consent. PROCEDURE

Lung samples will be obtained from surplus, healthy margin lung tissue resected from patients with suspected or confirmed lung cancer or from resected tissue from lung volume reduction surgery.

Cohort A: 10 participants with no COPD; Cohort B: 10 participants with COPD - chronic bronchitis; Cohort C: 10 participants with COPD emphysema

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Chronic obstructive pulmonary disease (COPD) is currently ranked as the third leading cause of death with an annual associated global healthcare cost of £1.3 trillion. It is the second most common cause of emergency hospital admissions with high morbidity and mortality. COPD results in a progressive loss of lung function, leading to respiratory failure. This loss of lung function is associated with repetitive cycles of inflammation and parenchymal scarring leading to the development of emphysema. This is a consequence of the breakdown of the delicate parenchymal structures and lung remodelling, with accumulation of fibrous tissue and loss of the alveolar-capillary functional units that are essential for effective gas exchange. Macroscopically the lungs become stiffer and unable to support the patient through the physiological inhalation/exhalation breathing cycles.

You may qualify if:

• Men or women aged over 18 years- .
• Must be competent to give written informed consent.
• Scheduled to undergo clinical indicated surgery to remove lung tissue.

You may not qualify if:

• Patient unable to give informed consent
• Significant long term condition or lung pathology (infection, asthma, fibrotic lung diseases) other than that for which they have been referred for surgery.
• Post Surgery
• Insufficient tissue removed to supply the laboratory study after consultation with the Consultant histopathologist.

Sponsors & Collaborators

• University Hospitals of North Midlands NHS Trust: lead

Study Sites (1)

University Hospitals of North Midlands NHS Trust

Stoke-on-Trent, Staffordshire, ST4 6QG, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITH DNA

Lung cells, including DASCp63/Krt5 with a possible role in disease pathology, will be isolated, expanded in vitro, characterised, and banked. Biomaterials will be selected and tested with regards to mechanical and physical properties and selected for use in the production of TELEs with properties matched to healthy and diseased lung tissue.

MeSH Terms

Conditions

Lung Neoplasms

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2021
• First Posted: May 7, 2021
• Study Start: August 31, 2017
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2025
• Last Updated: February 4, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)