Lung CancerNCT04878445
Tissue Engineering Approaches to Treat COPD
An observational study of Lung Cancer, run by University Hospitals of North Midlands NHS Trust at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Cancer
- What is being tested?
- Patients undergoing standard surgery, excess tissue only will be analysed with patient consent.
- Type of treatment
- Surgery or procedure
- How many people
- 30 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 31 Aug 2017to 31 Dec 2025
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University Hospitals of North Midlands NHS Trust
Stoke-on-Trent, Staffordshire, ST4 6QG
About this study
Official title: A Tissue Engineering Approach to Improve Lung Function and Clinical Outcome in Patients With COPD
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.
Read the detailed description
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 (1). 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 (2).
The presence of emphysema also results in the loss of lung elastic recoil as pockets of air form in place of damaged bronchioles and alveoli reducing the available volume for the next inhalation. The collapse of the airways during exhalation leads to increased lung volumes causing hyperinflation and gas trapping. Patients become progressively symptomatic with increasing breathlessness, reduced exercise tolerance and poor quality of life.
The pharmacological treatment options for emphysema are limited; current therapy aims to improve airflow limitation, reduce airway inflammation and reduce exacerbations, but does not reverse lung damage (3). Lung transplantation and lung volume reduction surgery (LVRS) is available for a selected minority of patients with severe emphysema. The recent introduction of non-invasive endoscopic mechanical treatment with Valves reduces severely damaged lung volume and re-directs air to the healthier tissue while Coils improves elastic lung recoil (4, 5). These interventions however do not improve survival.
Previous work performed within our laboratories has determined that hydrogel/elastin-based constructs can achieve mechanical values consistent with those of the alveolar wall when seeded with lung fibroblasts (1). This raises the intriguing question of whether tissue-engineered constructs (TEC) could be used to restore mechanical integrity of the emphysematous lung, via air pocket displacement and local integration, and ultimately by regeneration of local lung architecture.
Coupled to the work described above a recent observation went some way to detailing the mechanism behind the previously misunderstood, but physiologically critical, capacity for lung tissue to regenerate following on from acute disease such as pneumonia or acute respiratory distress syndrome (6). The key appears to lie with a population of distal airway stem cells who co-express Trp63 (p63) and Keratin 5 (Krt5). These DASCp63/Krt5 cells appear to migrate to sites of injury in the lung where they have demonstrated differentiation capacity including lineages such as type I and II pneumocytes and bronchiolar secretory cells. It is crucial to our understanding of chronic lung disorders, and design of future cell-based therapies, whether these cells remain present and dormant in diseased lung tissue or lost through as yet unknown mechanisms.
- Conditions
- Lung Cancer
- Being tested
- Patients undergoing standard surgery, excess tissue only will be analysed with patient consent.
- Medical subject headings
- Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Patients undergoing standard surgery, excess tissue only will be analysed with patient consent.Procedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). Receives: 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) . Receives: Procedure: Patients undergoing standard surgery, excess tissue only will be analysed with patient consent. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Through study completion upto 1 year
Secondary outcomes (1)
To achieve an understanding of the mechanical properties of diseased and healthy lung tissue.
To evaluate and tune hydrogel or foamed biomaterials to identify compositions which reflect the properties of healthy and diseased lung tissue.
S3) Creation of lung cell banks e.g. fibroblasts, pneumocytes, club cells, from diseased and healthy tissue.
S4). The identification of the presence/absence of DASCp63/Krt5 in healthy/diseased lung tissue and disease-association with retention of properties.
S5). Insertion of tissue engineered lung pieces into ex vivo lung slice culture and evaluation of cell spreading and construct integration.
Measured: Through study completion, upto 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2021
- Study start31 Aug 2017
- Primary completion31 Dec 2024
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospitals of North Midlands NHS Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04878445
- Sponsor's protocol ID
- 1517
- Status last verified
- Feb 2025
- First submitted
- 30 Apr 2021
- Last updated
- 4 Feb 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Tissue Engineering Approach to Improve Lung Function and Clinical Outcome in Patients With COPD
- ClinicalTrials.gov ID
- NCT04878445
- Acronym / sponsor ID
- 1517
- Conditions
- Lung Cancer
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University Hospitals of North Midlands NHS TrustUniversity, hospital or other
- Study start
- 31 Aug 2017 (actual)
- Primary completion
- 31 Dec 2024 (actual)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 7 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 (1). 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 (2).
The presence of emphysema also results in the loss of lung elastic recoil as pockets of air form in place of damaged bronchioles and alveoli reducing the available volume for the next inhalation. The collapse of the airways during exhalation leads to increased lung volumes causing hyperinflation and gas trapping. Patients become progressively symptomatic with increasing breathlessness, reduced exercise tolerance and poor quality of life.
The pharmacological treatment options for emphysema are limited; current therapy aims to improve airflow limitation, reduce airway inflammation and reduce exacerbations, but does not reverse lung damage (3). Lung transplantation and lung volume reduction surgery (LVRS) is available for a selected minority of patients with severe emphysema. The recent introduction of non-invasive endoscopic mechanical treatment with Valves reduces severely damaged lung volume and re-directs air to the healthier tissue while Coils improves elastic lung recoil (4, 5). These interventions however do not improve survival.
Previous work performed within our laboratories has determined that hydrogel/elastin-based constructs can achieve mechanical values consistent with those of the alveolar wall when seeded with lung fibroblasts (1). This raises the intriguing question of whether tissue-engineered constructs (TEC) could be used to restore mechanical integrity of the emphysematous lung, via air pocket displacement and local integration, and ultimately by regeneration of local lung architecture.
Coupled to the work described above a recent observation went some way to detailing the mechanism behind the previously misunderstood, but physiologically critical, capacity for lung tissue to regenerate following on from acute disease such as pneumonia or acute respiratory distress syndrome (6). The key appears to lie with a population of distal airway stem cells who co-express Trp63 (p63) and Keratin 5 (Krt5). These DASCp63/Krt5 cells appear to migrate to sites of injury in the lung where they have demonstrated differentiation capacity including lineages such as type I and II pneumocytes and bronchiolar secretory cells. It is crucial to our understanding of chronic lung disorders, and design of future cell-based therapies, whether these cells remain present and dormant in diseased lung tissue or lost through as yet unknown mechanisms.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort A: 10 participants with no COPD | – | Procedure: Patients undergoing standard surgery, excess tissue only will be analysed with patient consent.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). |
| Cohort B: 10 participants with COPD - chronic bronchitis | – | Procedure: Patients undergoing standard surgery, excess tissue only will be analysed with patient consent.Have a physician diagnosis of COPD with primarily a chronic bronchitis presentation (determined via CT, spirometry, histopathology, GOLD COPD classification). |
| Cohort C: 10 participants with COPD emphysema | – | Procedure: Patients undergoing standard surgery, excess tissue only will be analysed with patient consent.Have a physician diagnosis of COPD with primarily a emphysema presentation (determined via CT, spirometry, histopathology, GOLD COPD classification) . |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Patients undergoing standard surgery, excess tissue only will be analysed with patient consent.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. | Procedure or surgery | Cohort A: 10 participants with no COPD, Cohort B: 10 participants with COPD - chronic bronchitis, Cohort C: 10 participants with COPD emphysema |
Primary outcome
The overall aim of this project is to produce in vitro tissue engineered lung equivalents (TELEs) seeded with cells obtained from:
Time frame: Through study completion upto 1 year
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.
1 secondary outcome
To achieve an understanding of the mechanical properties of diseased and healthy lung tissue.
Time frame: Through study completion, upto 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Lung Cancer, run by University Hospitals of North Midlands NHS Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 4 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The overall aim of this project is to produce in vitro tissue engineered lung equivalents (TELEs) seeded with cells obtained from: (time frame: Through study completion upto 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2025.