Liver gene response to IV glucose during bariatric surgery in obese people with and without MASLD.

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This single-center, randomized 2 × 2 factorial trial uses bariatric (Roux-en-Y) surgery as an opportunity to deliver either a 35 g labeled-glucose bolus or saline and obtain paired tissue samples. Forty adults with severe obesity (20 with MASLD and 20 without MASLD) are randomized to glucose or saline; liver and multiple adipose biopsies are taken before and 45 minutes after infusion, with blood sampling and a one-time jejunal specimen collected. Primary analyses focus on single-cell RNA sequencing of liver biopsies to identify transcriptional changes triggered by the glucose challenge and to compare responses between MASLD and non-MASLD participants. Additional transcriptomic and microbiome profiling of jejunal tissue and adipose depots will contextualize hepatic findings.

Why it matters

Who can join: the full rules

Inclusion Criteria:

To be eligible to participate in this study, a subject must meet all of the following criteria:

Adult individuals, age \>35 \< 65 years old. Stable weight (no more than 3% TWL of initial body weight from screening to surgery) Subjects should be able to give informed consent Subjects agree to have tissue biopsies performed during surgery, that is 2 liver, subcutaneous, visceral and omental biopsies plus a one-time jejunal biopsy.

For obese non-MASLD patients:

* Adult individuals, age \>35 \< 65 years old.
* BMI ≥ 40 kg/m², or a BMI ≥ 35 kg/m² with an obesity-related comorbidity
* No MASLD based on Fibroscan
* Estimated glomerular filtration rate (eGFR) \> 60mL/min/1.73m2

For obese MASLD patients:

* MASLD diagnosis according to Fibroscan
* Compensated liver disease with the following hematologic and biochemical criteria on entry into study:

  * ALAT \<10x ULN
  * Hemoglobin \> 11g/dL for females and 12 g/dL for males
  * White blood cell (WBC) \> 2.5 K/ μL
  * Neutrophil count \> 1.5 K μL
  * Platelets \> 100 K/μL
  * Total bilirubin \<35 μmol/L
  * Albumin \>30 g/L
  * TP \>80% or INR \<1.4
  * Serum creatinine \<1.3 mg/dL (men) or \<1.1 mg/dL (women) or
* Estimated glomerular filtration rate (eGFR) \> 60mL/min/1.73m2

Exclusion Criteria:

A potential subject who meets any of the following criteria will be excluded from participation in this study:

* Use of metformin and SGLT2/ exogenous insulin/GLP-1 RA
* Primary lipid disorder
* Known genetic basis for insulin resistance or glucose intolerance
* All medical and psychiatric conditions except for obesity related diseases.
* Uncontrolled hypertension (RR \> 150/95 mmHg)
* Chronic kidney disease (creatinine \> 150 umol/L)
* Pregnancy, females who are breastfeeding
* Evidence of another form of liver disease
* History of sustained excess alcohol ingestion: daily consumption \>30g/day (3 drinks per day) for males and \>20 g/day (2 drinks per day) for females
* Significant systemic or major illnesses other than liver disease, including congestive heart failure (class C and D of the AHA), unstable coronary artery disease, cerebrovascular disease, pulmonary disease, kidney failure, organ transplantation, serious psychiatric disease, active malignancy, compromised immunity
* Body mass index (BMI) \>45 kg/m2
* Type 1 or type 2 diabetes
* Hemostasis disorders or current treatment with anticoagulants
* Known heart failure
* Contra-indication for liver biopsy History of/or current cardiac dysrhythmias and/or a history of cardiovascular events including myocardial infarction, except patients with only well-controlled hypertension

Where it's running

• Amc
  Amsterdam, North Holland, Netherlands Recruiting

Study contacts

• Principal investigator: Max Nieuwdorp, Prof. Dr. — Amsterdam UMC
• Study coordinator: Daniël P Baars, MD
• Email: d.p.baars@amsterdamumc.nl
• Phone: 0650063930

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Reset-INSPIRE: See if CGM can reveal insulin sensitivity in people at risk for MASLD

  This study tests whether real-time CGM data can accurately reflect insulin sensitivity in adults without diabetes who are at risk for MASLD.

  Recruiting National University Health System, Singapore · Singapore, Singapore · NCT07861191

• ALN-CIDEB in adults with MASLD to see if it helps the liver

  This study tests whether ALN-CIDEB can help adults with MASLD and its liver damage compared to placebo.

  Recruiting at 4 sites Phase 3 Regeneron Pharmaceuticals · Miami, Florida and 3 other locations · NCT07854782

• Peanut intake and liver health in adults with MASLD

  This study tests whether adding peanuts to daily meals for 12 weeks can improve liver markers and metabolic health in adults with MASLD.

  Recruiting Henry Ford Health System · Detroit, Michigan · NCT07646197

• Guided electronic tools to help clinicians manage MASLD

  Aimed at testing whether an electronic decision support tool used in primary care and specialty settings can help clinicians better manage MASLD in adults.

  Recruiting Vanderbilt University Medical Center · Nashville, Tennessee · NCT07382349

• Low‑methoxy pectin for inflammation, gut microbiome, and metabolic health in MASLD

  This tests whether taking daily low‑methoxy pectin for six weeks can reduce inflammation and improve gut bacteria and metabolic markers in adults with MASLD.

  Recruiting at 3 sites University of Nottingham · Nottingham, United Kingdom and 2 other locations · NCT07093346

• Digital early-warning system to predict acute lung injury after major liver surgery

  This study will try a machine-learning based warning tool to predict early acute lung injury in adults having major liver surgery.

  Recruiting at 4 sites Beijing Tsinghua Chang Gung Hospital · Beijing, Beijing Municipality and 3 other locations · NCT07070362

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.