Lung Transplant FailureNCT03089489
Lung PGD Biomarkers in Organ Donors
An observational study of Lung Transplant Failure, run by University Hospital of Mont-Godinne.
Trial summary
PGD is a syndrome characterized by alveolocapillary barrier structural and functional alterations with surfactant inactivation and vascular permeability increase, which cause lung edema, parenchymal infiltrate and progressive hypoxemia. PGD may be enhanced in lung donor. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Lung Transplant Failure
- What is being tested?
- lung biomarkers in organ donor for PGD in lung recipient
- How many people
- 50 participants
- Where
- No sites listed yet
- Study dates
- 1 Apr 2017to 8 Mar 2024
- Phase
- Observational
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: All lung donors and their lung recipients who reached the criteria for lung recovery and transplantation
Who may be able to join
- All organ donors and their lung recipients who reached the criteria for lung recovery and transplantation
Who cannot join
- None
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Role of Lung Surfactant Proteins in Donor Lung to Predict Primary Graft Dysfunction in Lung Recipients
PGD is a syndrome characterized by alveolocapillary barrier structural and functional alterations with surfactant inactivation and vascular permeability increase, which cause lung edema, parenchymal infiltrate and progressive hypoxemia.
PGD may be enhanced in lung donor. Inflammatory and structural changes may be present in the lungs before organ recovery and/or after organ preservation. The investigators aim to identify the surfactant protein, inflammatory and structural changes in lung donor before and after cold ischemia, and biomarkers to PGD in lung recipients.
Read the detailed description
Primary graft dysfunction (PGD) is responsible of high early mortality in lung transplanted patients.
Rationale
The evolution of lung transplantation may be complicated by primary graft dysfunction (PGD), a form of acute respiratory distress syndrome caused by ischemia-reperfusion-related phenomena. PGD occurs in 15-50% of cases and is responsible for a significant increase in mortality, duration of assisted ventilation and length of stay in intensive care. It is also an important risk factor for the medium-term development of acute and long-term rejection, of bronchiolitis obliterans syndrome (BOS) - chronic rejection - which drastically reduces the survival of the graft.
Surfactant proteins comprising the secretory protein of Clara cells (16-kd Clara cell protein-CC16) and surfactant proteins -A (SP-A), -B (SP-B) and -D (SP- D) are recognized as markers of the permeability of the alveolocapillary barrier.
Based on these findings, we postulate that the gene expression of CC16, SP-A, -B and D is altered in pulmonary biopsies performed in donors of patients developing primary graft dysfunction after pulmonary transplantation compared to those performed in the donors of patients free of this syndrome.
This study could therefore be a complementary means of objective assessment of lung quality prior to transplantation.
Aims and Objectives
- Describe, in the organ donor, changes in expression of Clara Cell Protein (CC16), surfactant-associated proteins (A, B or D), pro- and anti-inflammatory cytokines in circulating blood and lung tissue during organ recovery.
- Describe the biological and structural changes after the period of cold ischemia.
- Establish a correlation between biomarkers in the organ donor and the occurrence of acute graft dysfunction in the lung recipient.
Material and method
Inclusion Criteria
All lung organ donor patients referred to our network and their recipients will be included after obtaining their informed consent.
Data Collection
In the donor, we will record demographic data (age, sex), history, cause of death, blood gas measurement, chest x-ray protocol, blood biological parameters, duration of brain death if appropriate and hot ischemia time if appropriate and protocol of bacteriological analyzes.
In the recipient, we will record the demographic data (age, sex), indication of transplantation, results of right catheterization performed on pre-transplantation, standard intraoperative data, immunosuppression, Blood gas, chest x-ray protocol, filling balance and blood biological parameters at 24, 48 and 72h. The declamping times are recorded.
Patients are automatically followed up for the rest of their lives. Iterative biopsies are performed in the first year to detect possible acute rejection. The data will be included in our study.
Biological samples
In the donor, before the perfusion of the preservation solutions, 18 cc of peripheral blood are taken (dry tube, 9 cc). 1 tube will be stored at -80 ° C., the other will be centrifuged (15 minutes, 10000 / min, 20 ° C.) and then the serum will be stored at -80 ° C.
Immediately after lung recovery, a pulmonary biopsy (6 cm2) is performed at the lower lobes.
A fragment will be immediately placed in liquid nitrogen and stored at -80 ° C. A second fragment is stored in formalin for 24h and then stored in paraffin blocks.
Before implantation, at the end of the preservation period, a new lung biopsy is performed in the lower lobes.
Biological analyzes
Histological examination and gradation
Lung tissues fixed in formalin are stained with hematoxylin-eosin to gradate lung lesions [(1) neutrophil infiltration, (2) airway epithelial cell damage, (3) interstitial edema, (4) Hyaline membrane and (5) hemorrhage].
Inflammation, apoptosis and Surfactant proteins
O Tissue mRNA measurements: in real time Quantification PCR (RTQ-PCR)
O Tissue peptide measurements: Western Blot - ELISA - MILLIPLEX
O Treatment of blood samples and analyzes: ELISA - MILLIPLEX
Protein inflammatory cytokines (TNF-alpha, IL-6, IL-8, IL-1, IL33) (IL-10), intercellular adhesion molecules (ICAM-1, VCAM-1), apoptosis (Bax, Bcl2, Caspases)
Evaluation of apoptosis: TUNEL - Immunohistochemistry
- Conditions
- Lung Transplant Failure
- Being tested
- lung biomarkers in organ donor for PGD in lung recipient
- Keywords
- Primary graft dysfunction, Lung transplantation, Surfactant Protein, inflammation
- Medical subject headings
- Primary Graft Dysfunction, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
lung biomarkers in organ donor for PGD in lung recipientDiagnostic test
Lung biopsies in organ donor before and after cold ischemia
| Study group | Role | What they receive |
|---|---|---|
| Lung recipients with PGD | in the first 72 hours following lung transplantation, the lung recipients have blood gases and chest X-Ray to assess the occurrence of primary graft dysfunction. Chest X-Ray infiltrate and pathological PaO2/FiO2 ratio describe PGD occurence Receives: Diagnostic Test: lung biomarkers in organ donor for PGD in lung recipient | |
| Lung recipients PGD Free | In the first 72 hoours following lung transplantation, if the Cest X-ray is normal, the patient is considered PGD-free Receives: Diagnostic Test: lung biomarkers in organ donor for PGD in lung recipient |
What is being measured
The primary outcome is the main question the study is designed to answer.
Lung Biomarkers for primary graft dysfunction in organ donors
The investigators aim te describe lung donor structural and molecular changes in relation of PGD occurrence in recipient.
Measured: 5-7 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2017
- Study start1 Apr 2017 (estimated)
- Primary completion8 Mar 2022 (estimated)
- Study completion8 Mar 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung Transplant FailureStudies 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
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital of Mont-Godinne
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Asmae Belhaj, University Hospital of Mont-Godinne
- Investigators
- Asmae Belhaj, MD, PhD, Principal investigator, Centre Hospitalier Universitaire UCLouvain Namur
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03089489
- Sponsor's protocol ID
- B039201731131
- Status last verified
- Mar 2017
- First submitted
- 7 Mar 2017
- Last updated
- 24 Mar 2017
- Results posted
- No
- Data monitoring committee
- 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 24 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Lung Surfactant Proteins in Donor Lung to Predict Primary Graft Dysfunction in Lung Recipients
- ClinicalTrials.gov ID
- NCT03089489
- Acronym / sponsor ID
- B039201731131
- Conditions
- Lung Transplant Failure
- Keywords
- Primary graft dysfunction, Lung transplantation, Surfactant Protein, inflammation
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University Hospital of Mont-GodinneUniversity, hospital or other
- Study start
- 1 Apr 2017 (estimated)
- Primary completion
- 8 Mar 2022 (estimated)
- Study completion
- 8 Mar 2024 (estimated)
- First posted
- 24 Mar 2017 (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.
PGD is a syndrome characterized by alveolocapillary barrier structural and functional alterations with surfactant inactivation and vascular permeability increase, which cause lung edema, parenchymal infiltrate and progressive hypoxemia.
PGD may be enhanced in lung donor. Inflammatory and structural changes may be present in the lungs before organ recovery and/or after organ preservation. The investigators aim to identify the surfactant protein, inflammatory and structural changes in lung donor before and after cold ischemia, and biomarkers to PGD in lung recipients.
Detailed description
Primary graft dysfunction (PGD) is responsible of high early mortality in lung transplanted patients.
Rationale
The evolution of lung transplantation may be complicated by primary graft dysfunction (PGD), a form of acute respiratory distress syndrome caused by ischemia-reperfusion-related phenomena. PGD occurs in 15-50% of cases and is responsible for a significant increase in mortality, duration of assisted ventilation and length of stay in intensive care. It is also an important risk factor for the medium-term development of acute and long-term rejection, of bronchiolitis obliterans syndrome (BOS) - chronic rejection - which drastically reduces the survival of the graft.
Surfactant proteins comprising the secretory protein of Clara cells (16-kd Clara cell protein-CC16) and surfactant proteins -A (SP-A), -B (SP-B) and -D (SP- D) are recognized as markers of the permeability of the alveolocapillary barrier.
Based on these findings, we postulate that the gene expression of CC16, SP-A, -B and D is altered in pulmonary biopsies performed in donors of patients developing primary graft dysfunction after pulmonary transplantation compared to those performed in the donors of patients free of this syndrome.
This study could therefore be a complementary means of objective assessment of lung quality prior to transplantation.
Aims and Objectives
- Describe, in the organ donor, changes in expression of Clara Cell Protein (CC16), surfactant-associated proteins (A, B or D), pro- and anti-inflammatory cytokines in circulating blood and lung tissue during organ recovery.
- Describe the biological and structural changes after the period of cold ischemia.
- Establish a correlation between biomarkers in the organ donor and the occurrence of acute graft dysfunction in the lung recipient.
Material and method
Inclusion Criteria
All lung organ donor patients referred to our network and their recipients will be included after obtaining their informed consent.
Data Collection
In the donor, we will record demographic data (age, sex), history, cause of death, blood gas measurement, chest x-ray protocol, blood biological parameters, duration of brain death if appropriate and hot ischemia time if appropriate and protocol of bacteriological analyzes.
In the recipient, we will record the demographic data (age, sex), indication of transplantation, results of right catheterization performed on pre-transplantation, standard intraoperative data, immunosuppression, Blood gas, chest x-ray protocol, filling balance and blood biological parameters at 24, 48 and 72h. The declamping times are recorded.
Patients are automatically followed up for the rest of their lives. Iterative biopsies are performed in the first year to detect possible acute rejection. The data will be included in our study.
Biological samples
In the donor, before the perfusion of the preservation solutions, 18 cc of peripheral blood are taken (dry tube, 9 cc). 1 tube will be stored at -80 ° C., the other will be centrifuged (15 minutes, 10000 / min, 20 ° C.) and then the serum will be stored at -80 ° C.
Immediately after lung recovery, a pulmonary biopsy (6 cm2) is performed at the lower lobes.
A fragment will be immediately placed in liquid nitrogen and stored at -80 ° C. A second fragment is stored in formalin for 24h and then stored in paraffin blocks.
Before implantation, at the end of the preservation period, a new lung biopsy is performed in the lower lobes.
Biological analyzes
Histological examination and gradation
Lung tissues fixed in formalin are stained with hematoxylin-eosin to gradate lung lesions [(1) neutrophil infiltration, (2) airway epithelial cell damage, (3) interstitial edema, (4) Hyaline membrane and (5) hemorrhage].
Inflammation, apoptosis and Surfactant proteins
O Tissue mRNA measurements: in real time Quantification PCR (RTQ-PCR)
O Tissue peptide measurements: Western Blot - ELISA - MILLIPLEX
O Treatment of blood samples and analyzes: ELISA - MILLIPLEX
Protein inflammatory cytokines (TNF-alpha, IL-6, IL-8, IL-1, IL33) (IL-10), intercellular adhesion molecules (ICAM-1, VCAM-1), apoptosis (Bax, Bcl2, Caspases)
Evaluation of apoptosis: TUNEL - Immunohistochemistry
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lung recipients with PGD | – | Diagnostic Test: lung biomarkers in organ donor for PGD in lung recipientin the first 72 hours following lung transplantation, the lung recipients have blood gases and chest X-Ray to assess the occurrence of primary graft dysfunction. Chest X-Ray infiltrate and pathological PaO2/FiO2 ratio describe PGD occurence |
| Lung recipients PGD Free | – | Diagnostic Test: lung biomarkers in organ donor for PGD in lung recipientIn the first 72 hoours following lung transplantation, if the Cest X-ray is normal, the patient is considered PGD-free |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- All lung donors and their lung recipients who reached the criteria for lung recovery and transplantation
Key inclusion criteria (1 listed)
- All organ donors and their lung recipients who reached the criteria for lung recovery and transplantation
Key exclusion criteria (1 listed)
- None
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 |
|---|---|---|
| lung biomarkers in organ donor for PGD in lung recipientLung biopsies in organ donor before and after cold ischemia | Diagnostic test | Lung recipients PGD Free, Lung recipients with PGD |
Primary outcome
Lung Biomarkers for primary graft dysfunction in organ donors
Time frame: 5-7 years
The investigators aim te describe lung donor structural and molecular changes in relation of PGD occurrence in recipient.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2017.
- 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.
Asmae Belhaj, MD, PhD principal investigator
Centre Hospitalier Universitaire UCLouvain Namur
Questions about this trial
What is this clinical trial studying?
An observational study of Lung Transplant Failure, run by University Hospital of Mont-Godinne.
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 1 inclusion and 1 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: status not confirmed, as of the sponsor's last update on 24 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Asmae Behaj, MD, PhD (003281423153, asmae.belhaj@uclouvain.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Lung Biomarkers for primary graft dysfunction in organ donors (time frame: 5-7 years). 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 24 Mar 2017.