Impact of the Ex-vivo Pulmonary Perfusion System on the Microbiome of Lung Grafts and Their Inflammatory Reaction.

NCT06250517 | Unknown

• 1 other identifier: ExBioma
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

It is known that the interactions of the graft and recipient microbiome are capable of modulating immune responses, inducing resilience or exacerbation of various inflammatory or fibrotic processes, therefore variations in the lung microbiome are associated with immunological changes in the transplanted lung. The main objective is to understand the impact of new systems for conditioning and improving suboptimal lung grafts with ex vivo perfusion(EVLP) on the lung microbiome and its association with tissue inflammation. The hypothesis is that manipulation of lung grafts and perfusion with broad-spectrum antibiotics during EVLP conditioning changes the lung microbiome, conditioning a less pro-inflammatory environment. The methodology: This is a single-center prospective observational study. 7 consecutive brain-dead donors who do not meet the criteria to be lung donors will be included in the study. They will be carried out:

• P1. Detection: The donor without criteria to be a lung donor or rejected by all the transplant teams.
• P2. Extraction.
• P3. Cold preservation: The left lung will be cold-preserved
• P4. EVLP Conservation: The right lung will be prepared and conditioned for 3 hours using EVLP The following samples will be taken at two times:
• T0: At the end of the extraction
• Bronchoalveolar lavage (BAL): Before tracheal clamping, BAL will be taken from the left main bronchus using bronchoscopy. The BAL will be performed on the right lung just before starting P4.
• Lung biopsy: Lung biopsy of the lower lobe of both grafts will be performed
• Preservation liquid or Perfusion liquid: 20 mL of preservation liquid that is in contact with the left graft before storage, as a sterility control (P3) and 20 mL of perfusion liquid before conditioning, as a sterility control (P4).
• T1: At the end of the conservation protocols (P3 or P4).
• B.A.L.
• Lung biopsy: left lower lobe.
• Preservation liquid or Infusion liquid: 20 mL of preservation liquid that is in contact with the left graft or 20 mL of perfusion fluid. Due to the manipulation of the grafts during extraction and use of the technique, which involves extubating the donor and subsequently intubated again the grafts, as well as perfusion for a minimum of 3 hours with antibiotics, the use of EVLP could alter the microbiome of the grafts. This alteration could impact the obtaining of viable organs for transplant, in the immediate postoperative period as well as in the long-term results. There are no studies that analyse the change in the microbiome after conditioning with EVLP or its relationship with inflammatory parameters.

Conditions

Lung Transplant Failure

Outcome Measures

Primary Outcomes (6)

• Change in individual operational taxonomic units (OTUs) in lung parenchyma after the exvivo lung perfusion during 3 hours

  Analyse the lung microbiome and alpha diversity before the use of exvivo lung perfusion and after compared the micrological samples

  After 3 hours of perfusion in ex vivo lung perfusion

• Analysing with quantitative PCR of the genetic expression of 84 genes related to immune response in lung transplantation after the lung perfusion during 3h in exvivo lung perfusion system.

  Analyse with quantitative PCR of the genetic expression of 84 genes related with immune response in lung transplantation: CX3CR1, ICAM1, ITGA2, ITGAE, ITGAM, PECAM1, THBS1, THBS2, VCAM1, COL1A2, CCR5, CCR7, CD40, CD40LG, CD80, CD86, CTLA4, CXCR3, STAT4, TGFB1, CD44, CTGF, MMP1, MMP2, MMP7, MMP9, BMP7, CCL11, CCL2, CCL3, CCL4, CCL5, CSF2, CXCL10, IFNG, IL10, IL12A, IL13, IL16, IL1B, IL2, IL2RA, IL3, IL32, IL4, IL5, IL6, IL8, TNF, TGFB2, TGFB3, TIMP1, VEGFA, MS4A1, CXCL11, CXCL9, CXCR4, ADAM17, C3, CASP1, CASP3, CASP8, CCR2, CCR3, CD14, CD28, CD8A, FAS, FASLG, FCGR1A, GZMA, GZMB, NFKB1, NOS2, PRF1, PSMB9, STAT1, STAT6, TAP1, TLR3, TLR4, TLR9, TNFAIP3, TNFSF10 in lung samples before the use of exvivo lung perfusion and after, comparing them

  After 3 hours of perfusion in ex vivo lung perfusion

• Analyse the concentration of inflammatory cytokines after exvivo lung perfusion

  Analyse the concentration of inflammatory cytokines: IFN gamma,IL-1 beta,IL-6,IL-8 (CXCL8),IL-18,IP-10 (CXCL10),MCP-1 (CCL2),MIP-1 alpha (CCL3), TNF alpha,VEGF-D, with Luminex xMAP technique, in perfusion solution before and after the use of exvivo lung perfusion and comparing them

  After 3 hours of perfusion in ex vivo lung perfusion

• Change in individual operational taxonomic units (OTUs) in lung parenchyma after cold storage

  Analyse the lung microbiome and alpha diversity before and after the cold storage and compare the micrological samples.

  After 3 hours of cold storage

• Analysing the concentration of inflammatory citokines after cold storage

  Analyse the concentration of inflammatory cytokines: IFN gamma,IL-1 beta,IL-6,IL-8 (CXCL8),IL-18,IP-10 (CXCL10),MCP-1 (CCL2),MIP-1 alpha (CCL3), TNF alpha,VEGF-D, with Luminex xMAP technique, in perfusion solution before and after the cold storage and comparing them

  After 3 hours of cold storage

• Analysing with quantitative PCR of the genetic expression of 84 genes related to immune response in lung transplantation after cold storage

  Analyse with quantitative PCR of the genetic expression of 84 genes related with immune response in lung transplantation: CX3CR1, ICAM1, ITGA2, ITGAE, ITGAM, PECAM1, THBS1, THBS2, VCAM1, COL1A2, CCR5, CCR7, CD40, CD40LG, CD80, CD86, CTLA4, CXCR3, STAT4, TGFB1, CD44, CTGF, MMP1, MMP2, MMP7, MMP9, BMP7, CCL11, CCL2, CCL3, CCL4, CCL5, CSF2, CXCL10, IFNG, IL10, IL12A, IL13, IL16, IL1B, IL2, IL2RA, IL3, IL32, IL4, IL5, IL6, IL8, TNF, TGFB2, TGFB3, TIMP1, VEGFA, MS4A1, CXCL11, CXCL9, CXCR4, ADAM17, C3, CASP1, CASP3, CASP8, CCR2, CCR3, CD14, CD28, CD8A, FAS, FASLG, FCGR1A, GZMA, GZMB, NFKB1, NOS2, PRF1, PSMB9, STAT1, STAT6, TAP1, TLR3, TLR4, TLR9, TNFAIP3, TNFSF10 in lung samples before and after the cold storage, comparing them

  After 3 hours of cold storage

Study Arms (2)

EVLP

EXPERIMENTAL

Device: EVLP

Cold preservation

ACTIVE COMPARATOR

Device: Cold preservation

Interventions

EVLP DEVICE

The right lung will be perfused for 3h with EVLP

EVLP

Cold preservation DEVICE

The left lung will be cold preserved as usual protocol

Cold preservation

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• brain-death donors and donors after cardio circulatory death rejected for lung transplantation

You may not qualify if:

• Unilateral pneumonia
• Lack of consent for the donor's family.

Sponsors & Collaborators

• Vall d'Hebron Institute Research: lead
• Hospital Clinic of Barcelona: collaborator

Study Sites (1)

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

RECRUITING

MeSH Terms

Interventions

Cryopreservation

Intervention Hierarchy (Ancestors)

Tissue Preservation; Histocytological Preparation Techniques; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Preservation, Biological; Therapeutics; Investigative Techniques

Study Officials

• Irene Bello Rodríguez, Professor

  Hospital Clinic of Barcelona

  STUDY DIRECTOR

Central Study Contacts

Irene Bello Rodríguez, Professor

CONTACT

+34620664172; irene.bello.rodriguez@gmail.com

Alberto Sandiumenge Camps, Professor

CONTACT

+34639955585; albertosandiumenge@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 23, 2023
• First Posted: February 9, 2024
• Study Start: June 1, 2021
• Primary Completion: April 1, 2024
• Study Completion: June 1, 2024
• Last Updated: February 9, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)