Ignite Creation Date:
2024-05-06 @ 9:49 AM
Last Modification Date:
2024-10-26 @ 12:20 PM
Study NCT ID:
NCT03089489
Status:
UNKNOWN
Last Update Posted:
2017-03-24
First Post:
2017-03-07
Brief Title:
Lung PGD Biomarkers in Organ Donors
Sponsor:
University Hospital of Mont-Godinne
Organization:
University Hospital of Mont-Godinne
Study Overview
Official Title:
Role of Lung Surfactant Proteins in Donor Lung to Predict Primary Graft Dysfunction in Lung Recipients
Status:
UNKNOWN
Status Verified Date:
2017-03
Last Known Status:
NOT_YET_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 Inflammatory and structural changes may be present in the lungs before organ recovery andor 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
PGD may be enhanced in lung donor Inflammatory and structural changes may be present in the lungs before organ recovery andor 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
1 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
2 Describe the biological and structural changes after the period of cold ischemia
3 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
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
1 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
2 Describe the biological and structural changes after the period of cold ischemia
3 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None