Study of the Link Between MASH ( Metabolic Dysfunction-Associated Steatohepatitis) and MAMs (Mitochondria-Associated Membranes ) Alteration in Patients Undergoing Bariatric Surgery - MAMBA

Официальное название

Study of the Link Between Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Mitochondria-Associated Membranes (MAMs) Alteration in Patients Undergoing Bariatric Surgery - MAMBA

Обзор

The main research hypothesis is that alterations in the communication between the endoplasmic reticulum (ER) and the mitochondria at contact sites called mitochondria-associated membranes (MAMs) occurs in different hepatic cell types of patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MALSD) and is involved in the progression towards MASH and could also influence the process of improvement of MASH. This study aims to investigate the link between Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Mitochondria-Associated Membranes (MAMs) in liver cells and peripheral blood mononuclear cells (PBMCs) in patients undergoing bariatric surgery. The primary objective is to analyze MAMs alterations in hepatocytes in MASH patients compared to non-MASH patients. Secondary objectives include evaluating the correlation between MAMs in PBMCs and liver cells and assessing MAMs changes post-bariatric surgery.

Вмешательства

• Процедура Bariatric surgery (Sleeve Gastrectomy or Gastric Bypass)
  Patients undergoin bariatric surgery with simultaneous liver biopsy to analyze MAMs alterations in liver and PBMCs. Follow-up assessments at 6 and 12 months.

Первичные конечные точки

• MAMs alterations in hepatocytes [Срок оценки: Baseline (T0)]

Вторичные конечные точки (5)

• MAMs alterations in non-parenchymal liver cells (T0) [Срок оценки: Baseline (T0)]
• MAMs alterations in PBMCs (T0, T6, T12 months) [Срок оценки: Baseline (T0) , T6, T12 months]
• Changes in hepatic markers of MASLD post-surgery [Срок оценки: T0 to T6, T6 to T12, T0 toT12 (months)]
• Changes in hepatic markers of MASLD post-surgery (2) [Срок оценки: T0 to T6, T6 to T12, T0 toT12 (months)]
• Correlation between MASH improvement and MAMs changes [Срок оценки: T0-T12 months]

Критерии участия

• Inclusion Criteria \* :

• Female or male adult patients
• Patient who has benefited from a pluridisciplinary evaluation (medical, surgical, psychiatric), with a favorable opinion for a sleeve gastrectomy or a gastric bypass.
• Patient with an indication Indication for intraoperative liver biopsy due to suspected MASH
• Patient who agrees to be included in the study and who signs the informed consent form,
• Patient affiliated to a healthcare insurance plan.
• Exclusion Criteria \* :

• Patient presenting Hepatitis B as defined as presence of hepatitis B surface antigen (HBsAg).
• Patient presenting previous or current infection with Hepatitis C
• Autoimmune hepatitis as defined by anti-nuclear antibody (ANA) of 1:160 or greater and liver histology consistent with autoimmune hepatitis or previous response to immunosuppressive therapy.
• Patient presenting Autoimmune cholestatic liver disorders as defined by elevation of alkaline phosphatase and anti-mitochondrial antibody of greater than 1:80 or liver histology consistent with primary biliary cirrhosis or elevation of alkaline phosphatase and liver histology consistent with sclerosing cholangitis.
• Patient presenting Wilson disease as defined by ceruloplasmin below the limits of normal and liver histology consistent with Wilson disease.
• Patient presenting Alpha-1-antitrypsin deficiency as defined by alpha-1-antitrypsin level less than normal and liver histology consistent with alpha-1-antitrypsin deficiency.
• Patient presenting Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D.
• Patient presenting Drug-induced liver disease as defined on the basis of typical exposure and history.
• Patient presenting Bile duct obstruction as shown by imaging studies.
• History of ingestion of medications known to produce steatosis, such as corticosteroids, high-dose estrogen, tamoxifen, methotrexate, amiodarone or tetracycline in the previous 6 months.
• Evidence of cirrhosis or previously known cirrhosis based on the results from previous liver biopsy or history of portal hypertension presented by ascites, hepatic encephalopathy or varices
• Consommation régulière et/ou excessive d'alcool (plus de 30g/j pour les hommes et plus de 15 g/j pour les femmes) sur une période de plus de 2 ans au cours des 10 dernières années.
• History of known HIV infection
• History of type 1 diabetes
• Pregnant women or breastfeeding mothers\*.
• Minor patient
• Patient deprived of liberty,
• Patients under psychiatric care
• Patients admitted to a health or social care establishment for purposes other than research
• Mentally unbalanced patients, under supervision or guardianship,
• Patients not affiliated to a social security scheme or benefiting from a similar scheme
• Patient who does not understand French/ is unable to give consent,
• Patient already included in a trial who may interfere with the study

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Франция · 2 центра

• Hospices Civils de Lyon - Hôpital Edouard Herriot — Lyon
• Centre Hospitalier Lyon Sud, Endocrinologie, Diabète et nutrition — Pierre-Bénite

Идентификаторы

NCT: NCT06868992 · 69HCL24_1096 · 2024-A02591-46

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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