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Monocytic Expression of HLA-DR After Liver Transplantation (EdMonHG)

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ClinicalTrials.gov Identifier: NCT03995537
Recruitment Status : Recruiting
First Posted : June 24, 2019
Last Update Posted : March 2, 2020
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon

Tracking Information
First Submitted Date June 20, 2019
First Posted Date June 24, 2019
Last Update Posted Date March 2, 2020
Actual Study Start Date February 26, 2020
Estimated Primary Completion Date September 26, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: February 27, 2020)
number of receptors expressed by monocytes [ Time Frame: 7 months ]
Primary outcome will be the kinetics of HLA-DR expression on the monocytes / macrophages surface during the first month after LT as a function of pre-LT status (Nadir, normalization delay of HLA-DR expression) and its association with 2 clinical events reflecting post-LT immune dysfunction (acute cell rejection and sepsis). Expression of HLA-DR is measured by the number of receptors expressed by monocytes and measured by flow cytometry at different times: at inclusion (D0), the day of LT and twice a week for 1 month in post LT.
Original Primary Outcome Measures
 (submitted: June 20, 2019)
number of receptors expressed by monocytes [ Time Frame: 4 months ]
Primary outcome will be the kinetics of HLA-DR expression on the monocytes / macrophages surface during the first month after LT as a function of pre-LT status (Nadir, normalization delay of HLA-DR expression) and its association with 2 clinical events reflecting post-LT immune dysfunction (acute cell rejection and sepsis). Expression of HLA-DR is measured by the number of receptors expressed by monocytes and measured by flow cytometry at different times: at inclusion (D0), the day of LT and twice a week for 1 month in post LT.
Change History
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Monocytic Expression of HLA-DR After Liver Transplantation
Official Title Monocytic Expression of HLA-DR After Liver Transplantation
Brief Summary

A defect of the immune response has been described in patients with severe liver disease. This immune-paresis is partly driven by a compensatory anti-inflammatory response following a systemic inflammatory response syndrome and affects the innate immune response. The innate immune defect has been described in patients with advanced cirrhosis and more significantly in patients with acute liver failure or acute on chronic liver failure (ACLF). The monocytes/macrophages pro-inflammatory response and finally the antimicrobial response are thus strongly impaired, leading to higher sepsis risk. The monocytes/macrophages phenotype associated with these functional alterations has been widely described, with a weaker expression of Human Leukocyte Antigen - DR isotype (HLA-DR) on the monocytes surface, correlated with poor outcomes. The low monocytic expression of HLA-DR, its functional and clinical impact has been widely described in the context of septic shock with similar pathophysiological mechanisms.

Liver transplantation (LT) is often the only therapeutic option for patients with advanced liver failure. Post-transplant survival of the most severe patients is similar to the survival in the whole population of LT patients, but the complication rate remains higher, with a major risk of infection. Currently used immunosuppression protocols do not take into account the quality of pre-transplant immune response. Some treatments, such as corticosteroids, which are widely used for the induction of post-transplant immunosuppression, may affect the innate immune response. However, it has been shown that low expression of post-transplant monocyte HLA-DR was associated with a greater risk of septic complication.

The general objective of this study is to focus on the evolution of a robust marker of immune dysfunction, HLA-DR monocyte expression, before and following LT, and to analyse its post LT expression depending on the level of pre-transplant expression as well as its association with post-transplant complications. This study will bring new insights for the design of a prospective study on the relevance of adapting post-transplant immunosuppression protocols to HLA-DR expression on monocytes surface, which is a robust marker of the innate immune response.

Evaluation of innate immune dysfunction pre-LT by quantification of monocytic HLA-DR expression and monitoring of its post-LT kinetics may be relevant for assessing post-transplant immune status and adapting immunosuppressive therapy. A descriptive, observational study associating clinical and biological data is needed to confirm the relevance of HLA-DR expression quantification on the surface of monocytes in a population of selected patients, before and after LT. These data will allow setting up a prospective interventional study reporting the possible benefit of post-transplant immunosuppressive treatment modulation, according to the HLA-DR monocyte dosage and its kinetics evolution.

The main objective of this study is to describe the association between evolution of monocytic HLA-DR expression on monocytes/macrophages surface during the first month after LT and the occurrence of one of the 2 following clinical events reflecting a post LT immune dysfunction (acute cell rejection and sepsis).

Detailed Description Not Provided
Study Type Observational
Study Design Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples Without DNA
Description:

One samples of Ethylenediaminetetraacetic acid (EDTA) (4 millilitre (mL)), one Heparin sample (4mL) and one PAXgene® sample (2.5mL) will be collected:

  • at inclusion
  • between inclusion and LT in case of major clinical change
  • During the pre-transplant follow-up 3 months after inclusion, for patients who have not been transplanted within 3 months following inclusion. At 6 months post-inclusion, non-transplanted patients will terminate the study prematurely
  • at day 1 after LT
  • 2 times a week after the LT for a maximum of 1 month
Sampling Method Non-Probability Sample
Study Population Patients with severe liver disease waiting for LT. Only patients with the most frequent LT indications will be eligible: complicated cirrhosis of hepatocellular carcinoma (HCC), acute or chronic decompensation of cirrhosis, with or without multi-visceral failure and fulminant hepatitis.
Condition
  • Liver Diseases
  • Liver Transplantation
  • Cirrhosis, Liver
Intervention Biological: blood sample

Samples will be collected at the inclusion and repeated if necessary before LT, including one 4 mL EDTA sample and one 4 mL Heparin sample and one 2.5 mL PAXgene® sample, allowing the HLA-DR assay to be performed with also plasma aliquots and messenger RNAs.

Same samples will also be collected :

  • between inclusion and LT in case of major clinical change
  • During the pre-transplant follow-up 3 months after inclusion, for patients who have not been transplanted within 3 months after inclusion
  • at day 1 after LT
  • 2 times a week after the LT for a maximum of 1 month

Biological data will be collected at those different times.

Study Groups/Cohorts Patients with severe liver disease waiting liver transplant
Only patients with the most frequent LT indications will be eligible: complicated cirrhosis of hepatocellular carcinoma (HCC), acute or chronic decompensation of cirrhosis, with or without multi-visceral failure and fulminant hepatitis.
Intervention: Biological: blood sample
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: February 27, 2020)
100
Original Estimated Enrollment
 (submitted: June 20, 2019)
60
Estimated Study Completion Date September 26, 2021
Estimated Primary Completion Date September 26, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Patients waiting for LT in the LT center of the Groupement Hospitalier Nord, Hospices Civils de Lyon, presenting :

    • Cirrhosis

      • Complicated with hepatocellular carcinoma
      • Or chronically decompensated (recurrent gastrointestinal bleeding, refractory ascites, portopulmonary or hepatopulmonary syndrome, chronic liver failure)
      • Or with acute decompensation, with or without multi-visceral failure
    • Or fulminant hepatitis
  • Patient eligible for the standard immunosuppression protocol (induction with anti-Interleukin-2 (IL2) (Day1 and Day4) and then corticosteroids for a minimum of 7 days associated with tacrolimus and mycophenolate mofetil)
  • Patient having theoretical access to LT within <3 months (head of local and / or national waiting list)

Exclusion Criteria:

  • Minor or adult patient under tutorship or curatorship
  • Pregnant and lactating woman
  • Patient without liberty
  • Patient not affiliated to social security
  • Refusal to participate in the study
  • Patient enrolled in "super-emergency" outside working days
  • Patients waiting for LT without underlying liver disease (healthy liver HCC, cholangiocarcinoma, primary tumor metastases, amyloidosis, Rendu Osler disease, dominant biliary disease such as recurrent angiocholitis without underlying cirrhosis)
  • Patient who already had a LT
  • Patient who received a multi-organ transplant (liver + kidney / heart / lung / intestine)
  • Patient on immunosuppressive therapy before hepatic transplant (other than corticosteroids)
  • Patient not eligible for standard immunosuppression protocol
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Fanny Lebossé, MD,PhD 04 26 10 93 39 ext +33 fanny.lebosse@chu-lyon.fr
Listed Location Countries France
Removed Location Countries  
 
Administrative Information
NCT Number NCT03995537
Other Study ID Numbers 69HCL19_0116
2019-A00954-53 ( Other Identifier: ID-RCB )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party Hospices Civils de Lyon
Study Sponsor Hospices Civils de Lyon
Collaborators Not Provided
Investigators Not Provided
PRS Account Hospices Civils de Lyon
Verification Date February 2020