2014TP001 - Assessing the Biology of the Injured Lung - Version 1
July 27, 2023 updated by: Manchester University NHS Foundation Trust
Assessing the Biology of the Injured Lung - Version 1
Respiratory diseases are very common and are the third leading cause of death in England. As such, there is strong interest in understanding how respiratory disease occurs.
This study intends to understand the changes that occur within diseased/injured lungs obtained from humans. The end goal of this will be to create new drugs to help treat these disorders.
Diseased lungs will be obtained from patients receiving a lung transplant. Lungs will either be placed onto a heart-lung machine, or surgically cut in order to create a model of the lung that can be used experimentally in the laboratory. Using a heart-lung machine, lungs can be maintained outside of the human body for a maximum of 12 hours, allowing the direct assessment of the organ. Using this procedure, we aim to understand the processes that occur within a disease, as well as during repair. Using the model of the lung, we will look at how the body's immune system interacts within a diseased lung.
Study Overview
Status
Completed
Conditions
Study Type
Observational
Enrollment (Actual)
119
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
- Adult
- Older Adult
Accepts Healthy Volunteers
No
Sampling Method
Non-Probability Sample
Study Population
Respiratory disorders - lung transplantation
Description
Inclusion Criteria:
- Patients must be able to provide informed consent
- Patients must be aged between 18-80 years of age
Exclusion Criteria:
-Patients under 16 or over 70 years of age
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 |
|---|---|---|
|
To identify the mechanisms that occur during lung inflammation, injury and repair and the contribution of immune cells to these processes.
Time Frame: Prior to lung transplantation.
|
Cytokines and chemokines within lungs will be assessed to determine inflammatory profiles.
This will be done using luminex arrays that allow quantification of a range of immunologic molecules in bronchoalveolar lavage and perfusate samples.
This will provide a broad overview of the prevailing local tissue environment.
We will also assess this following immunomodulation as this may be significantly altered by the presence of immunomodulatory therapeutics.
|
Prior to lung transplantation.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Characterise the migration and functional profile of immune cells within the inflamed/damaged lung.
Time Frame: Prior to lung transplantation
|
Immune cells obtained from the lungs on the EVLP circuit and cells cultured in the air liquid model will be incubated with antibodies that target specific cellular markers for the detection using flow cytometry.
Immune cells can then be characterised and their function determined.
The behavioural characteristics and activation status of immune cells will also be determined using flow cytometry, ELISpot/ELISA, immunohistochemistry and qPCR.
|
Prior to lung transplantation
|
|
Assess the effectiveness of therapeutic agents that can repair lung damage.
Time Frame: Prior to lung transplantation
|
Diseased lungs that have been removed from patients during their transplantation will be used as a model to explore novel therapeutic interventions that can modulate inflammation and induce tissue remodelling within the lungs.
The entire lungs will be placed within the EVLP circuit and perfused with an acellular solution.
Different therapeutic agents will be introduced to the lungs during EVLP and lung function will be monitored.
We will determine if lungs have improved via a clinically relevant improvement in lung function (this is the international standard for lung function assessment during EVLP).
|
Prior to lung transplantation
|
|
Trial therapeutic agents that can modulate the effect of immune cells in response to lung tissue injury.
Time Frame: Prior to lung transplantation
|
Diseased lungs that have been removed from patients during their transplantation will be used as a model to explore novel therapeutic interventions that can modulate inflammation and induce tissue remodelling within the lungs.
The entire lungs will be placed within the EVLP circuit and perfused with an acellular solution.
Different therapeutic agents will be introduced to the lungs during EVLP and lung function will be monitored.
We will determine if lungs have improved via a clinically relevant improvement in lung function (this is the international standard for lung function assessment during EVLP).
|
Prior to lung transplantation
|
|
Identify new therapeutic targets/agents that can reduce the incidence/severity of inflammatory respiratory conditions.
Time Frame: Prior to lung transplantation
|
PDiseased lungs that have been removed from patients during their transplantation will be used as a model to explore novel therapeutic interventions that can modulate inflammation and induce tissue remodelling within the lungs.
The entire lungs will be placed within the EVLP circuit and perfused with an acellular solution.
Different therapeutic agents will be introduced to the lungs during EVLP and lung function will be monitored.
We will determine if lungs have improved via a clinically relevant improvement in lung function (this is the international standard for lung function assessment during EVLP).
|
Prior to lung transplantation
|
|
Cut sections of the lung to culture in an in vitro lung model to assess the effect of various different mechanisms of injury on the function and characteristics of immune cells.
Time Frame: Prior to lung transplantation
|
Lungs will be dissected to be used in an in vitro model, generating a morphologically accurate model of the lung.
This model will then be used to assess immune cell characteristics.
|
Prior to lung transplantation
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
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)
August 29, 2014
Primary Completion (Actual)
April 4, 2019
Study Completion (Actual)
April 4, 2019
Study Registration Dates
First Submitted
July 27, 2023
First Submitted That Met QC Criteria
July 27, 2023
First Posted (Actual)
August 7, 2023
Study Record Updates
Last Update Posted (Actual)
August 7, 2023
Last Update Submitted That Met QC Criteria
July 27, 2023
Last Verified
July 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2014TP001
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
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.