Luminal Fructose Kinetics (MARTINI Study)
NCT Number: NCT06539494
Acronym: MARTINI
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: MASLD
Interventions: DRUG: Omeprazole 40 MG
Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 22
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: BASIC_SCIENCE
Start Date: 2024-07-01
Completion Date: 2026-04
Locations: Amsterdam UMC location AMC, Amsterdam, Netherlands

Summary:
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.

Primary Outcome Measures: Changes in ethanol concentrations before and after omeprazol usage, mM (serum, intestinal fluid, urine and feces), four weeks|Changes in fructose concentrations in peripheral blood before and after omeprazol usage, Area under the curve of fructose in peripheral blood upon ingestion of 1 gram / kg unlabeled fructose in combination with 1000mg of D-fructose-13C6 measured during fructose challange test, 4 weeks|Changes in fructose metabolites in breath before and after omeprazol usage, Area under the curve of various metabolites (e.g. ethanol) will be measured in breath samples upon ingestion of 1 gram / kg unlabeled fructose in combination with 1000mg of D-fructose-13C6 measured during fructose challange test, 4 weeks|Fructose metabolites in feces before and after omeprazol usage, Using 24h feces, the investigators will measure fecal concentrations of fructose metabolites such as ethanol, as well as short chain fatty acids (SCFAs) and bile acids., 4 weeks|Fructose metabolites in urine, Using 24h urine, the investigators will measure fecal concentrations of fructose metabolites such as ethanol, as well as SCFAs and bile acids., 4 weeks|Changes in serum glucose concentrations before and after omeprazol, mmol/l measured during fructose challange test, 4 weeks
Secondary Outcome Measures: Changes in microbiota composition in luminal samples, changes in relative abundance (%) of bacterial phyla, genera and species between groups and after intervention with omeprazol measured by 16sRNA sequencing and shotgun metagenome analysis, four weeks|Changes in dietary intake, Participants are asked to fill out an online dietary questionnaire for the 3 days prior to study visits, four weeks|Bioreactor analyses, Using specific anaerobic culturing, ethanol production of fecal samples will be assessed of bacterial strains., four weeks|Changes in Oral microbiota composition, changes in relative abundance (%) of bacterial phyla, genera and species between groups and after intervention with omeprazol measured by 16sRNA sequencing., four weeks|Differences in gene expression in small intestinal biopsies, measured by RNA sequencing, 4 weeks|Changes in Fecal microbiota composition, changes in relative abundance (%) of bacterial phyla, genera and species between groups and after intervention with omeprazol measured by 16sRNA sequencing and shotgun metagenome analysis, 4 weeks|Changes in abundance of post prandial plasma metabolites, Postprandial plasma samples will be prepared for the analysis of mainly: organic acids, amino acids, fatty acids, uric acid, glucose and fructose before and after intervention with omeprazol, 4 weeks