Transplantation, Heart-LungCLADNCT02863835
Evaluation of Electrical Impedance Tomography for the Diagnosis of Chronic Rejection in Lung Transplants Recipients
A study testing EIT and Salbutamol nebulisation and with CPAP in people with Transplantation, Heart-Lung and Chronic Lung Allograft Dysfunction, run by Guy's and St Thomas' NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
Electrical impedance tomography (EIT) is non-invasive and provides functional imaging of the lung and it could be a useful tool to diagnose chronic lung allograft dysfunction (CLAD) and specially Bronchiolitis Obliterans Syndrome (BOS). Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Transplantation, Heart-Lung, Chronic Lung Allograft Dysfunction, Bronchiolitis Obliterans Syndrome
- What is being tested?
- EIT and Salbutamol nebulisation and with CPAP
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Apr 2016to Jun 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Bilateral lung transplant recipient
- Time from lung transplantation > 6 months
- A chest CT scan (HRCT) performed as part of their standard care in the last 3 months
- A bronchoscopy with BAL and Biopsies performed as part of their standard care in the last 3 months
- For group with CLAD: a drop in lung function assessed on FEV1 or FVC
- For group without CLAD: an unchanged lung function
Who cannot join
- Pregnancy
- Body mass index > 40kg/m2
- Significant physical or psychiatric comorbidity that would prevent compliance with trial protocol
- Allergy to salbutamol
- Patient with intra-bronchial or intra-tracheal metallic stent
- Evidence of acute infection or acute cellular rejection.
- In addition 10 healthy volunteers will be recruited
Trial locations and contacts
1 site in 1 country.
About this study
Electrical impedance tomography (EIT) is non-invasive and provides functional imaging of the lung and it could be a useful tool to diagnose chronic lung allograft dysfunction (CLAD) and specially Bronchiolitis Obliterans Syndrome (BOS). Hence, for this study, the investigators aim to show that EIT would provide an accurate diagnostic CLAD with an ability to to distinguish BOS from Restrictive Allograft Syndrome (RAS) and to stage BOS accurately when compared to FEV1 the current gold standard. The investigators are also aiming to provide physiological data in lung transplant recipients with chronic rejection.
Read the detailed description
Lung transplantation is the only treatment option available for patients affected by end-stage lung diseases such as chronic obstructive pulmonary disease (COPD), cystic fibrosis or idiopathic pulmonary fibrosis, not responding to maximal medical therapy. Despite the advance in the surgical techniques, immunosuppression treatment and prevention of acute cellular rejection episodes as well as opportunistic infections, the long terms outcomes following lung transplant remain unsatisfactory. Chronic lung allograft dysfunction (CLAD) is the first cause of long term mortality in lung transplant recipients responsible of 5 years mortality post-surgery of 50%. CLAD can lead to chronic respiratory failure and can presents in two different phenotypes: Restrictive forms of CLAD were all lung volumes are decreased (commonly called RAS, Restrictive Allograft Syndrome) that has been recently associated with antibodies mediated rejection. A more common form of obstructive CLAD has been identified as the well-known and defined Bronchiolitis Obliterans Syndrome (BOS). In patients with BOS, the progressive obliteration and a narrowing of the distal airways result in breathlessness, airflow obstruction and air trapping.
Currently, Forced Expiratory Volume at 1 second (FEV1) measurement is the gold standard to assess BOS severity. This test is non invasive and easily performed at bedside. Thus, it only gives a broad idea of the regional consequences of BOS as may be influenced by large airway obstructions. Chest computed tomography (CT) gives more detailed imaging of the regional consequences of BOS but is time-consuming and expose patients to radiations. Others imaging techniques such as ventilation/perfusion scintigraphy have been studied but cannot be performed at bedside.
As to date there is no curative treatment for BOS, preventive treatments such as long term azithromycin, bronchodilators, inhaled steroids or plasmapheresis have to be started at early stage of the disease to improve outcomes for the recipients Electrical impedance tomography (EIT) is a new technology that involves wearing a belt of sensors around the chest that provides information on how well the lungs are being filled with air by the ventilator. It allows the assessment of these differences, which previously required the use of invasive equipment to obtain. Information is gained by repeatedly injecting small alternating electric currents (usually 5 mA) at high frequency of 50 - 80 kHz through a system of skin electrodes (usually 16) applied circumferentially around the thorax in a single plane between the 4th and 6th intercostal space. While an adjacent pair of electrodes 'injects' the current ('adjacent drive configuration'), all the remaining adjacent passive electrode pairs measure the differences in electric potential. A resistivity (impedance) image is reconstructed from this data by a mathematical algorithm using a two dimensional model and a simplified shape to represent the thoracic cross-section.
The resulting image possesses a high temporal and functional resolution making it possible to monitor dynamic physiological phenomena (e.g. delay in regional inflation or recruitment) on a breath by breath basis. It is important to realize that the EIT images are based on image reconstruction techniques that require at least one measurement on a well-defined reference state. All quantitative data are related to this reference and can only indirectly quantify (relative) changes in local lung impedance (but not absolute).
EIT can be used in mechanically ventilated patients to assess recruitment and to optimise ventilator settings to reduce risk of iatrogenic ventilator associated lung injury. To date, EIT has never been used in lung transplant recipients.
- Conditions
- Transplantation, Heart-Lung, Chronic Lung Allograft Dysfunction, Bronchiolitis Obliterans Syndrome
- Being tested
- EIT, Salbutamol nebulisation and with CPAP
- Medical subject headings
- Bronchiolitis Obliterans Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EITOther
All participants will have continuous monitoring of EIT whilst self venting
Salbutamol nebulisation and with CPAPOther
All participants will have continuous monitoring - salbutamol nebulisation will be given during 15 minutes using 5mg of salbutamol. Assessments on CPAP will be performed at 3 different level of pressure during this time.
| Study group | Role | What they receive |
|---|---|---|
| Intervention 1 | Experimental | A 1:1 randomisation will be performed to decide the order of the administration of salbutamol and CPAP. All participants will receive both interventions in a cross-over fashion. Salbutamol nebulisation will be given during 15 minutes using 5mg of salbutamol. Assessments on CPAP will be performed at 3 different level of pressure.
Each participant will then have continuous assessment of the following whilst self venting:
* Spirometry - FEV1, FVC, MVV
* Muscle strength measurements: MIP, MEP, SNIP
* Borg scale, mMRC, Visual Analogue Scale for breathlessness
* Electrical impedance tomography
* EMGpara
* Transcutaneous measurement of CO2 and 02 level
* End-tidal CO2 monitoring
* Pneumotachography Receives: Other: EIT; Other: Salbutamol nebulisation and with CPAP |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of chronic lung allograft dysfunction in lung transplant recipients identified with EIT
Using EIT to diagnose chronic lung allograft dysfunction in lung transplant recipients
Measured: 1 day
Restrictive and obstructive phenotypes in recipients of lung transplants.
Using EIT to distinguish between restrictive and obstructive different phenotypes in recipients of lung transplants
Measured: 1 day
Secondary outcomes (5)
Change in EIT results following administration of salbutamol and CPAP
Following administration of salbutamol whilst using CPAP taking EITresults to determine if there is a change in the lungs
Measured: 1 day
Correlation EIT results and chest-CT results
Comparing Lung measurements taken during the EIT test with the CT results of the participants to ascertain if there is any correlation
Measured: 1 day
Neural respiratory drive (EMGpara) of lung transplant recipients
Comparing lung measurements taken during the EIT test with those taken during neural respiratory drive during the intervention
Measured: 1 day
Correlation between EIT and neural respiratory drive results with breathlessness
Comparing lung measurements taken during the EIT test with the Neural respiratory drive results taken and the participants breathlessness
Measured: 1 day
Correlation of EIT results found in obstructive and restrictive allograft syndrome
Comparing the obstructive allograft syndrome EIT results to the restrictive allograft syndrome results.
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2016 (estimated)
- Study startApr 2016
- Primary completionJun 2017
- Study completionJun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Transplantation, Heart-LungStudies of the same condition, open and under way.
- More trials run by Guy's and St Thomas' NHS Foundation TrustThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Guy's and St Thomas' NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- ADIR Association
- Responsible party
- Sponsor
- Investigators
- Nick Hart, Study chair, Guy's and St Thomas' NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02863835
- Sponsor's protocol ID
- 16/LO/0198
- Acronym
- CLAD
- Status last verified
- May 2018
- First submitted
- 4 May 2016
- Last updated
- 29 May 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Electrical Impedance Tomography for the Diagnosis of Chronic Rejection in Lung Transplants Recipients
- ClinicalTrials.gov ID
- NCT02863835
- Acronym / sponsor ID
- CLAD / 16/LO/0198
- Conditions
- Transplantation, Heart-Lung, Chronic Lung Allograft Dysfunction, Bronchiolitis Obliterans Syndrome
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Guy's and St Thomas' NHS Foundation TrustUniversity, hospital or other
- Collaborators
- ADIR Association
- Study start
- Apr 2016
- Primary completion
- Jun 2017 (actual)
- Study completion
- Jun 2017 (actual)
- First posted
- 11 Aug 2016 (estimated)
- 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.
Electrical impedance tomography (EIT) is non-invasive and provides functional imaging of the lung and it could be a useful tool to diagnose chronic lung allograft dysfunction (CLAD) and specially Bronchiolitis Obliterans Syndrome (BOS). Hence, for this study, the investigators aim to show that EIT would provide an accurate diagnostic CLAD with an ability to to distinguish BOS from Restrictive Allograft Syndrome (RAS) and to stage BOS accurately when compared to FEV1 the current gold standard. The investigators are also aiming to provide physiological data in lung transplant recipients with chronic rejection.
Detailed description
Lung transplantation is the only treatment option available for patients affected by end-stage lung diseases such as chronic obstructive pulmonary disease (COPD), cystic fibrosis or idiopathic pulmonary fibrosis, not responding to maximal medical therapy. Despite the advance in the surgical techniques, immunosuppression treatment and prevention of acute cellular rejection episodes as well as opportunistic infections, the long terms outcomes following lung transplant remain unsatisfactory. Chronic lung allograft dysfunction (CLAD) is the first cause of long term mortality in lung transplant recipients responsible of 5 years mortality post-surgery of 50%. CLAD can lead to chronic respiratory failure and can presents in two different phenotypes: Restrictive forms of CLAD were all lung volumes are decreased (commonly called RAS, Restrictive Allograft Syndrome) that has been recently associated with antibodies mediated rejection. A more common form of obstructive CLAD has been identified as the well-known and defined Bronchiolitis Obliterans Syndrome (BOS). In patients with BOS, the progressive obliteration and a narrowing of the distal airways result in breathlessness, airflow obstruction and air trapping.
Currently, Forced Expiratory Volume at 1 second (FEV1) measurement is the gold standard to assess BOS severity. This test is non invasive and easily performed at bedside. Thus, it only gives a broad idea of the regional consequences of BOS as may be influenced by large airway obstructions. Chest computed tomography (CT) gives more detailed imaging of the regional consequences of BOS but is time-consuming and expose patients to radiations. Others imaging techniques such as ventilation/perfusion scintigraphy have been studied but cannot be performed at bedside.
As to date there is no curative treatment for BOS, preventive treatments such as long term azithromycin, bronchodilators, inhaled steroids or plasmapheresis have to be started at early stage of the disease to improve outcomes for the recipients Electrical impedance tomography (EIT) is a new technology that involves wearing a belt of sensors around the chest that provides information on how well the lungs are being filled with air by the ventilator. It allows the assessment of these differences, which previously required the use of invasive equipment to obtain. Information is gained by repeatedly injecting small alternating electric currents (usually 5 mA) at high frequency of 50 - 80 kHz through a system of skin electrodes (usually 16) applied circumferentially around the thorax in a single plane between the 4th and 6th intercostal space. While an adjacent pair of electrodes 'injects' the current ('adjacent drive configuration'), all the remaining adjacent passive electrode pairs measure the differences in electric potential. A resistivity (impedance) image is reconstructed from this data by a mathematical algorithm using a two dimensional model and a simplified shape to represent the thoracic cross-section.
The resulting image possesses a high temporal and functional resolution making it possible to monitor dynamic physiological phenomena (e.g. delay in regional inflation or recruitment) on a breath by breath basis. It is important to realize that the EIT images are based on image reconstruction techniques that require at least one measurement on a well-defined reference state. All quantitative data are related to this reference and can only indirectly quantify (relative) changes in local lung impedance (but not absolute).
EIT can be used in mechanically ventilated patients to assess recruitment and to optimise ventilator settings to reduce risk of iatrogenic ventilator associated lung injury. To date, EIT has never been used in lung transplant recipients.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intervention 1 | Experimental | Other: EIT, Other: Salbutamol nebulisation and with CPAPA 1:1 randomisation will be performed to decide the order of the administration of salbutamol and CPAP. All participants will receive both interventions in a cross-over fashion. Salbutamol nebulisation will be given during 15 minutes using 5mg of salbutamol. Assessments on CPAP will be performed at 3 different level of pressure. Each participant will then have continuous assessment of the following whilst self venting: * Spirometry - FEV1, FVC, MVV * Muscle strength measurements: MIP, MEP, SNIP * Borg scale, mMRC, Visual Analogue Scale for breathlessness * Electrical impedance tomography * EMGpara * Transcutaneous measurement of CO2 and 02 level * End-tidal CO2 monitoring * Pneumotachography |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Bilateral lung transplant recipient
- Time from lung transplantation > 6 months
- A chest CT scan (HRCT) performed as part of their standard care in the last 3 months
- A bronchoscopy with BAL and Biopsies performed as part of their standard care in the last 3 months
- For group with CLAD: a drop in lung function assessed on FEV1 or FVC
Key exclusion criteria (7 listed)
- Pregnancy
- Body mass index > 40kg/m2
- Significant physical or psychiatric comorbidity that would prevent compliance with trial protocol
- Allergy to salbutamol
- Patient with intra-bronchial or intra-tracheal metallic stent
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 |
|---|---|---|
| EITAll participants will have continuous monitoring of EIT whilst self venting | Other | Intervention 1 |
| Salbutamol nebulisation and with CPAPAll participants will have continuous monitoring - salbutamol nebulisation will be given during 15 minutes using 5mg of salbutamol. Assessments on CPAP will be performed at 3 different level of pressure during this time. | Other | Intervention 1 |
Primary outcome
Number of chronic lung allograft dysfunction in lung transplant recipients identified with EIT
Time frame: 1 day
Using EIT to diagnose chronic lung allograft dysfunction in lung transplant recipients
Restrictive and obstructive phenotypes in recipients of lung transplants.
Time frame: 1 day
Using EIT to distinguish between restrictive and obstructive different phenotypes in recipients of lung transplants
5 secondary outcomes
Change in EIT results following administration of salbutamol and CPAP
Time frame: 1 day
Correlation EIT results and chest-CT results
Time frame: 1 day
Neural respiratory drive (EMGpara) of lung transplant recipients
Time frame: 1 day
Correlation between EIT and neural respiratory drive results with breathlessness
Time frame: 1 day
Correlation of EIT results found in obstructive and restrictive allograft syndrome
Time frame: 1 day
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2018.
- 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.
Nick Hart study chair
Guy's and St Thomas' NHS Foundation Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing EIT and Salbutamol nebulisation and with CPAP in people with Transplantation, Heart-Lung and Chronic Lung Allograft Dysfunction, run by Guy's and St Thomas' NHS Foundation 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 6 inclusion and 7 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: finished, as of the sponsor's last update on 29 May 2018. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Number of chronic lung allograft dysfunction in lung transplant recipients identified with EIT (time frame: 1 day). The study lists 2 primary outcomes in all. 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 29 May 2018.