Luminal Fructose Kinetics (MARTINI Study)

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Status and phase: Enrolling; Phase 2

Conditions: MASLD

Treatments: Drug: Omeprazole 40 MG

Study type: Interventional

Funder types: Other

Identifiers

NCT06539494

NL85966.018.23

Details and patient eligibility

About

In this study the investigators aim is to explore the dynamics of (small) intestinal fructose catabolism in humans and ethanol production in relation to small intestinal signalling pathways and changes in pH, using 13C fructose isotope tracing techniques complemented with direct luminal sampling via small intestinal catheter in biopsy proven MASLD/MASH patients vs healthy (BMI<25) subjects. Additionally the investigators will repeat the experiment after four weeks of administering omeprazole at a dose of 40 mg twice daily. Omeprazole is a proton pump inhibitor, known to elevate pH from 2-6.

Full description

The investigators will perform a non blinded single centre intervention study in 2x 11 participants

Participants will be either healthy volunteers with a BMI < 25 and Age 18-65 or patients with MASLD with a BMI >25, Age 18-65

The objective of the investigators is to study the fructose host/microbial kinetics in humans and to establish the role of (small) intestinal pH on fructose fermentation and endogenous ethanol production in a MASLD/MASH population versus healthy subjects

Subjects will be given omeprazole orally given twice a day 40mg for four weeks

At baseline and after four weeks of omeprazole, a fructose challenge test with labelled fructose and fomepizole and a gastroscopy will be performed, during which a nasal-intestinal catheter will be placed to allow for luminal sampling during the fructose challenge test.

Enrollment: 22 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

In case of the healthy subject group:

• Adult individuals, age > 18 <65 years
• Male or postmenopauzal females
• BMI <25
• Ability to give informed consent In case of the MASLD/MASH group
• Adult individuals, age > 18 <65 years
• Male or postmenopauzal females
• BMI > 25
• Biopsy proven MASLD/MASH
• Ability to give informed consent

Exclusion criteria

• 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
• Patients with diabetes
• Bariatric surgery
• Other forms of liver disease (e.g. Hepatitis B,C, Wilson disease, hemochromatosis)
• Proton-pump inhibitor usage one year prior to study participation
• GLP1, SGLT2i or insulin use
• Antibiotic use for the past 3 months
• Probiotic or symbiotic usage
• Pregnant women
• Chronic illness (including a known history of heart failure, renal failure (eGFR <30 ml/min), pulmonary disease, gastrointestinal disorders, or hematologic diseases), or other inflammatory diseases
• Active infection
• Use of ascal, clopidogrel or other platelet inhibition
• Smoking
• Blood thinners
• Heart failure

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

22 participants in 2 patient groups

Healthy volunteer

Active Comparator group

Description:

healthy volunteers who will get omeprazol daily 2dd40 mg for 4 weeks

Treatment:

Drug: Omeprazole 40 MG

Sujbects with MASLD

Active Comparator group

Description:

Patients with MASLD who will get omeprazol daily 2dd40 mg for 4 weeks

Treatment:

Drug: Omeprazole 40 MG