Clinical trial NCT06539494: Luminal Fructose Kinetics (MARTINI Study)
Official title: Luminal Fructose Kinetics (MARTINI) (2024)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: MASLD
Keywords: Fructose
MASLD
Ethanol
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
First posted: 2024-08-06
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 2x 11 participants will be given the same intervention (omeprazol daily)
Primary purpose: BASIC_SCIENCE

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Changes in ethanol concentrations before and after omeprazol usage
timeFrame: four weeks
measure: Changes in fructose concentrations in peripheral blood before and after omeprazol usage
timeFrame: 4 weeks
measure: Changes in fructose metabolites in breath before and after omeprazol usage
timeFrame: 4 weeks
measure: Fructose metabolites in feces before and after omeprazol usage
timeFrame: 4 weeks
measure: Fructose metabolites in urine
timeFrame: 4 weeks
measure: Changes in serum glucose concentrations before and after omeprazol
timeFrame: 4 weeks
Secondary outcomes:
measure: Changes in microbiota composition in luminal samples
timeFrame: four weeks
measure: Changes in dietary intake
timeFrame: four weeks
measure: Bioreactor analyses
timeFrame: four weeks
measure: Changes in Oral microbiota composition
timeFrame: four weeks
measure: Differences in gene expression in small intestinal biopsies
timeFrame: 4 weeks
measure: Changes in Fecal microbiota composition
timeFrame: 4 weeks
measure: Changes in abundance of post prandial plasma metabolites
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC location AMC
Study officials:
affiliation: Amsterdam UMC, location AMC
name: Max Nieuwdorp, prof
role: PRINCIPAL_INVESTIGATOR
References: