Liver gene response to IV glucose during bariatric surgery in obese people with and without MASLD.
Glucose IV and Its Hepatic Outcomes After a Metabolic Stress Test During Bariatric Surgery in Obese Patients With and Without MASLD
This trial will test whether giving sugar through a vein changes liver gene activity during bariatric surgery in people with obesity who do or do not have MASLD.
Quick facts
| Phase | Not applicable |
|---|---|
| Study type | Interventional |
| Enrollment | 40 (estimated) |
| Ages | 35 Years to 65 Years |
| Sex | All |
| Sponsor | Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) Academic / other |
| Locations | 1 site (Amsterdam, North Holland) |
| Trial ID | NCT07326865 on ClinicalTrials.gov |
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.
Who should consider this trial
Good fit: Adults aged 35–65 with severe obesity who are scheduled for Roux-en-Y gastric bypass, can consent to intraoperative tissue biopsies, meet BMI and basic lab criteria, and either have or do not have MASLD by Fibroscan are the intended participants.
Not a fit: People not undergoing bariatric surgery, outside the 35–65 age range, with decompensated liver disease, significant kidney impairment, or unwilling to have intraoperative biopsies are unlikely to benefit from or be eligible for this protocol.
Why it matters
Potential benefit: If successful, the study could reveal specific molecular responses to glucose in MASLD that point to new targets or strategies for diagnosis and treatment.
How similar studies have performed: The specific combination of an intraoperative labeled-glucose challenge with paired pre/post liver biopsies and single-cell RNA sequencing in humans is largely novel, though related fasting-biopsy and metabolic challenge studies have provided supporting background.
Eligibility criteria
Show full inclusion / exclusion 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
Where this trial is running
Amsterdam, North Holland
- 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
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.