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

NCT06868992 | Recruiting

• 2 other identifiers: 69HCL24_10962024-A02591-46
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Metabolic Dysfunction-Associated Steatohepatitis; Sleeve Gastrectomy; Gastric Bypass Surgery; Metabolic Dysfunction-Associated Steatotic Liver Disease

Keywords

MASH; MASLD; Mitochondria-Associated Membranes (MAMs); Bariatric Surgery; Hepatic Fibrosis

Outcome Measures

Primary Outcomes (1)

• MAMs alterations in hepatocytes

  Number of MAM contacts in liver cells at baseline (T0)

  Baseline (T0)

Secondary Outcomes (5)

• MAMs alterations in non-parenchymal liver cells (T0)

  Baseline (T0)

• MAMs alterations in PBMCs (T0, T6, T12 months)

  Baseline (T0) , T6, T12 months

• Changes in hepatic markers of MASLD post-surgery

  T0 to T6, T6 to T12, T0 toT12 (months)

• Changes in hepatic markers of MASLD post-surgery (2)

  T0 to T6, T6 to T12, T0 toT12 (months)

• Correlation between MASH improvement and MAMs changes

  T0-T12 months

Study Arms (1)

Bariatric Surgery Group

Patients with MASLD undergoing bariatric surgery (sleeve gastrectomy or gastric bypass) with an indication for liver biopsy due to suspected MASH

Procedure: Bariatric surgery (Sleeve Gastrectomy or Gastric Bypass)

Interventions

Bariatric surgery (Sleeve Gastrectomy or Gastric Bypass) PROCEDURE

Patients undergoin bariatric surgery with simultaneous liver biopsy to analyze MAMs alterations in liver and PBMCs. Follow-up assessments at 6 and 12 months.

Bariatric Surgery Group

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult patients with MASLD and obesity for whom an indication for bariatric surgery AND the indication for a per-procedure liver biopsy during bariatric surgery is indicated because of the suspected presence of MASH

You may qualify if:

• 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.

You may not qualify if:

• 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\*.

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (2)

Hospices Civils de Lyon - Hôpital Edouard Herriot

Lyon, France, 69003, France

RECRUITING

Centre Hospitalier Lyon Sud, Endocrinologie, Diabète et nutrition

Pierre-Bénite, France, 69495, France

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Biobank (blood, urine, faeces) Tissue biobank (adipose tissue, muscle) Tissue biobank (liver)

MeSH Terms

Conditions

Liver Cirrhosis

Interventions

Bariatric Surgery; Gastric Bypass

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Bariatrics; Obesity Management; Therapeutics; Surgical Procedures, Operative; Gastroenterostomy; Anastomosis, Surgical; Digestive System Surgical Procedures

Central Study Contacts

Cyrielle CAUSSY, Pr

CONTACT

+33 4 78 86 44 48; cyrielle.caussy@chu-lyon.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2025
• First Posted: March 11, 2025
• Study Start: April 15, 2025
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028
• Last Updated: January 15, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2)