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Muscles in Liver Diseases (UNIVERSE)

Primary Purpose

Patients Having a Scheduled Abdominal Surgery Procedure

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
blood samples
biopsy of abdominal paroie
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Patients Having a Scheduled Abdominal Surgery Procedure

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients over the age of 18 having a scheduled abdominal surgery at Beaujon Hospital
  • Patient affiliated to a social security scheme
  • Informed patient having signed a consent to participate

Exclusion Criteria:

Primary muscle disease (myopathy, dermatopolymyositis, vasculitis with muscle involvement)

  • Amyotrophic drugs: long-term corticosteroid therapy
  • Immunosuppressive treatments
  • Chronic inflammatory disease (example: Crohn's disease)
  • Disease known to cause sarcopenia such as -but not limited to- active extrahepatic neoplasia, polycystic hepatorenal disease
  • Gastrointestinal haemorrhage in the 15 days prior to inclusion
  • Acute alcoholic hepatitis in the month before inclusion
  • Infection during treatment
  • Pregnant or breastfeeding woman
  • Protected populations: people under guardianship or under guardianship
  • Patient not affiliated to a social security scheme
  • Patient under AME
  • Patient not having signed consent

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm Type

    Other

    Other

    Other

    Other

    Arm Label

    patients without liver disease,

    patient with chronic liver disease without cirrhosis,

    patients with compensated cirrhosis,

    patient with severe cirrhosis

    Arm Description

    taking blood samples and biopsy of muscular wall

    taking blood samples and biopsy of muscular wall

    taking blood samples and biopsy of muscular wall

    taking blood samples and biopsy of muscular wall

    Outcomes

    Primary Outcome Measures

    describe the muscle changes that occur during liver disease.
    Assessment of the histology of the muscle removed during abdominal surgery by measuring the diameter of muscle fibers
    describe the muscle changes that occur during liver disease.
    Assessment of the histology of the muscle removed during abdominal surgery, by evaluating the vascularity with measurements of CD31 count and αSMA count
    describe the muscle changes that occur during liver disease.
    Assessment of the histology of the muscle removed during abdominal surgery by evaluating the muscle stem cells with measurements of Pax7, MyoD and Myogenin
    describe the muscle changes that occur during liver disease.
    Assessment of the histology of the muscle removed during abdominal surgery by evaluating gene expression with transcriptomics

    Secondary Outcome Measures

    Identify circulating mediators that could be responsible for sarcopenia: released by the liver and acting on the muscle.
    Circulating concentration of mediators / cells suspected of being responsible for sarcopenia: extracellular vesicles released by the liver lymphocyte phenotype potentially modified by sinusoidal endothelial cells of the liver protein array
    Identify circulating mediators that could be responsible for complications of liver disease: released by the muscle and acting on the different organs
    Circulating concentration of mediators / cells suspected of being released by muscle and contributing to organ dysfunction in liver disease: extracellular vesicles myokines

    Full Information

    First Posted
    January 7, 2021
    Last Updated
    February 15, 2021
    Sponsor
    Assistance Publique - Hôpitaux de Paris
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04758793
    Brief Title
    Muscles in Liver Diseases
    Acronym
    UNIVERSE
    Official Title
    Muscles in Liver Diseases
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    December 2020
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    February 15, 2021 (Anticipated)
    Primary Completion Date
    May 31, 2026 (Anticipated)
    Study Completion Date
    May 31, 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Assistance Publique - Hôpitaux de Paris

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    Cirrhosis is the 11th leading cause of death in the world. The progression to cirrhosis occurs as a result of chronic hepatic injury, related to excessive alcohol consumption, non-alcoholic steatohepatitis, chronic viral infection. Cirrhosis is accompanied by symptoms that profoundly affect the quality of life of patients. Sarcopenia, or decrease in muscle capacity through loss of muscle mass, is associated with liver disease. Patients with liver disease and sarcopenia have increased morbidity, and higher pre- and post-liver transplant mortality than patients without sarcopenia. The mechanism responsible for the development of sarcopenia in liver disease remains largely misunderstood, as do the mechanisms by which sarcopenia appears to promote complications of liver disease. This study, carried out on a prospective cohort of patients with liver disease, aims at understanding the pathophysiological mechanisms involved in sarcopenia and its consequences.
    Detailed Description
    Cirrhosis is the 11th leading cause of death in the world. The progression to cirrhosis occurs as a result of chronic hepatic injury, related to excessive alcohol consumption, non-alcoholic steatohepatitis, and chronic viral infection. Cirrhosis is accompanied by symptoms that profoundly affect the quality of life of patients. Sarcopenia, or decrease in muscle capacity through loss of muscle mass, is associated with liver disease. Patients with liver disease and sarcopenia have increased morbidity, and higher pre- and post-liver transplant mortality than patients without sarcopenia. The mechanism responsible for the development of sarcopenia in liver disease remains largely misunderstood, as do the mechanisms by which sarcopenia appears to promote complications of liver disease. This study, carried out on a prospective cohort of patients with stable liver disease, aims at understanding the pathophysiological mechanisms involved in sarcopenia and its consequences. After checking the inclusion criteria, all eligible patients treated at Beaujon Hospital (Clichy) will be invited to participate in the study. After inclusion, clinical and laboratory features (hepatic assessment) will be collected and the blood samples will be taken. During the surgery, a muscle biopsy will be performed on the incision area. No follow-up is planned.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Patients Having a Scheduled Abdominal Surgery Procedure

    7. Study Design

    Primary Purpose
    Basic Science
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    260 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    patients without liver disease,
    Arm Type
    Other
    Arm Description
    taking blood samples and biopsy of muscular wall
    Arm Title
    patient with chronic liver disease without cirrhosis,
    Arm Type
    Other
    Arm Description
    taking blood samples and biopsy of muscular wall
    Arm Title
    patients with compensated cirrhosis,
    Arm Type
    Other
    Arm Description
    taking blood samples and biopsy of muscular wall
    Arm Title
    patient with severe cirrhosis
    Arm Type
    Other
    Arm Description
    taking blood samples and biopsy of muscular wall
    Intervention Type
    Other
    Intervention Name(s)
    blood samples
    Intervention Description
    3 citrated tubes and 3 EDTA tubes
    Intervention Type
    Other
    Intervention Name(s)
    biopsy of abdominal paroie
    Intervention Description
    a muscle biopsy will be performed on the incision area
    Primary Outcome Measure Information:
    Title
    describe the muscle changes that occur during liver disease.
    Description
    Assessment of the histology of the muscle removed during abdominal surgery by measuring the diameter of muscle fibers
    Time Frame
    1 month after the of inclusion
    Title
    describe the muscle changes that occur during liver disease.
    Description
    Assessment of the histology of the muscle removed during abdominal surgery, by evaluating the vascularity with measurements of CD31 count and αSMA count
    Time Frame
    1 month after the of inclusion
    Title
    describe the muscle changes that occur during liver disease.
    Description
    Assessment of the histology of the muscle removed during abdominal surgery by evaluating the muscle stem cells with measurements of Pax7, MyoD and Myogenin
    Time Frame
    1 month after the of inclusion
    Title
    describe the muscle changes that occur during liver disease.
    Description
    Assessment of the histology of the muscle removed during abdominal surgery by evaluating gene expression with transcriptomics
    Time Frame
    1 month after the of inclusion
    Secondary Outcome Measure Information:
    Title
    Identify circulating mediators that could be responsible for sarcopenia: released by the liver and acting on the muscle.
    Description
    Circulating concentration of mediators / cells suspected of being responsible for sarcopenia: extracellular vesicles released by the liver lymphocyte phenotype potentially modified by sinusoidal endothelial cells of the liver protein array
    Time Frame
    1 month after the of inclusion
    Title
    Identify circulating mediators that could be responsible for complications of liver disease: released by the muscle and acting on the different organs
    Description
    Circulating concentration of mediators / cells suspected of being released by muscle and contributing to organ dysfunction in liver disease: extracellular vesicles myokines
    Time Frame
    1 month after the of inclusion

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Patients over the age of 18 having a scheduled abdominal surgery at Beaujon Hospital Patient affiliated to a social security scheme Informed patient having signed a consent to participate Exclusion Criteria: Primary muscle disease (myopathy, dermatopolymyositis, vasculitis with muscle involvement) Amyotrophic drugs: long-term corticosteroid therapy Immunosuppressive treatments Chronic inflammatory disease (example: Crohn's disease) Disease known to cause sarcopenia such as -but not limited to- active extrahepatic neoplasia, polycystic hepatorenal disease Gastrointestinal haemorrhage in the 15 days prior to inclusion Acute alcoholic hepatitis in the month before inclusion Infection during treatment Pregnant or breastfeeding woman Protected populations: people under guardianship or under guardianship Patient not affiliated to a social security scheme Patient under AME Patient not having signed consent
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    pierre Emmanuel Rautou
    Phone
    140875283
    Ext
    33
    Email
    pierre.emmanuel.rautou@aphp.fr
    First Name & Middle Initial & Last Name or Official Title & Degree
    Enis Kostallari
    Phone
    140875283
    Ext
    33
    Email
    enis.kostallari@gmail.com

    12. IPD Sharing Statement

    Plan to Share IPD
    Undecided

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    Muscles in Liver Diseases

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