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Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT03089489
Other study ID # B039201731131
Secondary ID
Status Not yet recruiting
Phase N/A
First received March 7, 2017
Last updated March 17, 2017
Start date April 1, 2017
Est. completion date March 8, 2024

Study information

Verified date March 2017
Source University Hospital of Mont-Godinne
Contact Asmae Behaj, MD, PhD
Phone 003281423153
Email asmae.belhaj@uclouvain.be
Is FDA regulated No
Health authority
Study type Observational

Clinical 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. 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.


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


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 50
Est. completion date March 8, 2024
Est. primary completion date March 8, 2022
Accepts healthy volunteers No
Gender All
Age group 18 Years to 80 Years
Eligibility Inclusion Criteria:

- All organ donors and their lung recipients who reached the criteria for lung recovery and transplantation

Exclusion Criteria:

Study Design


Related Conditions & MeSH terms


Intervention

Diagnostic Test:
lung biomarkers in organ donor for PGD in lung recipient
Lung biopsies in organ donor before and after cold ischemia

Locations

Country Name City State
n/a

Sponsors (1)

Lead Sponsor Collaborator
University Hospital of Mont-Godinne

Outcome

Type Measure Description Time frame Safety issue
Primary 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. 5-7 years
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