Clinical trial

Hepatic Gene Response to Intravenous Glucose in Obese Patients With and Without MASLD Undergoing Bariatric Surgery

Recruiting now · Not applicable · 1 countries · Registry ID NCT07326865

Recruiting nowNot applicableInterventional

What this study is about

The goal of this clinical trial is to learn how the liver responds to sugar in people with obesity who are having bariatric surgery. Researchers want to understand differences between people with and without metabolic associated steatotic liver disease (MASLD). The main question is: Does giving sugar directly into the vein change how liver genes work in people with and without MASLD? Researchers will compare: * People with MASLD who receive sugar * People with MASLD who receive saline (salt water) * People without MASLD who receive sugar * People without MASLD who receive saline During surgery, participants will: * Receive either a sugar solution (35 grams of glucose in 150 mL fluid) or saline * Have small samples (biopsies) taken from the liver and fat tissue before and 45 minutes after the infusion * Provide blood samples to measure sugar, insulin, and other metabolites * Provide a one-time sample of intestinal tissue that is normally removed during surgery This study may help explain why MASLD develops and how the liver reacts to sugar. The results could lead to new ways to understand and treat liver disease in people with obesity.

A promising-looking record is not the same as confirmed eligibility. The study team must review the full criteria and current recruitment status.

Basic eligibility

Age35 Years to 65 Years

SexAll

Healthy volunteersNot accepted

ConditionMASLD

Full registry criteria

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

Treatments and study arms

[6,6-D2]-labeled glucose (intravenous)

Other

Participants receive a 35-gram intravenous bolus of \[6,6-D2\]-labeled glucose dissolved in 150 mL solution. The infusion is administered at the start of bariatric surgery over 3-5 minutes via an indwelling catheter. Liver and adipose tissue biopsies are collected before infusion and 45 minutes after infusion to assess transcriptomic changes. Blood samples are taken at multiple timepoints to measure glucose, insulin, and plasma metabolites, metabolites can be traced using the labeled glucose.

Saline (0.9% sodium chloride infusion)

Other

Participants receive an intravenous infusion of 150 mL saline (0.9% sodium chloride) at the start of bariatric surgery. The infusion is administered over 3-5 minutes via an indwelling catheter. Liver and adipose tissue biopsies are collected before infusion and 45 minutes after infusion to serve as controls for transcriptomic and metabolic changes.

Primary outcomes

Change from baseline in hepatic gene expression at 45 minutes after intravenous glucose bolus compared to saline infusionBaseline (pre-infusion, at start of surgery) to 45 minutes after infusion during bariatric surgery

Liver biopsies are collected at two timepoints: (1) baseline, immediately after anesthesia induction and before infusion, and (2) 45 minutes after infusion of either \[6,6-D2\]-labeled glucose or saline. Single-cell RNA sequencing (scRNA-seq) is performed on these paired samples to measure changes in hepatic gene expression. The primary comparison is the difference in transcriptomic profiles between baseline and 45 minutes post-infusion, stratified by MASLD status (confirmed by Fibroscan and histology). Gene expression changes are quantified as fold-change in transcript abundance, normalized to baseline values.

Study locations

1 locations were listed when this page was built. The first 40 are shown.

AMC🇳🇱 Amsterdam, North Holland, Netherlands

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Daniël P BaarsContact

Email · Call 0650063930