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NCT Number: NCT06539494

Luminal Fructose Kinetics (MARTINI Study)

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.

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Key information

Conditions

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Omeprazole 40 MG

Drug

Proton pump inhibitor twice a day for 4 weeks

Primary outcomes

  1. Changes in ethanol concentrations before and after omeprazol usage

    Time frame: four weeks

    mM (serum, intestinal fluid, urine and feces)

  2. Changes in fructose concentrations in peripheral blood before and after omeprazol usage

    Time frame: 4 weeks

    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

  3. Changes in fructose metabolites in breath before and after omeprazol usage

    Time frame: 4 weeks

    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. Fructose metabolites in feces before and after omeprazol usage

    Time frame: 4 weeks

    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.

  5. Fructose metabolites in urine

    Time frame: 4 weeks

    Using 24h urine, the investigators will measure fecal concentrations of fructose metabolites such as ethanol, as well as SCFAs and bile acids.

  6. Changes in serum glucose concentrations before and after omeprazol

    Time frame: 4 weeks

    mmol/l measured during fructose challange test

Secondary outcomes

  1. Changes in microbiota composition in luminal samples

    Time frame: four weeks

    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

  2. Changes in dietary intake

    Time frame: four weeks

    Participants are asked to fill out an online dietary questionnaire for the 3 days prior to study visits

  3. Bioreactor analyses

    Time frame: four weeks

    Using specific anaerobic culturing, ethanol production of fecal samples will be assessed of bacterial strains.

  4. Changes in Oral microbiota composition

    Time frame: four weeks

    changes in relative abundance (%) of bacterial phyla, genera and species between groups and after intervention with omeprazol measured by 16sRNA sequencing.

  5. Differences in gene expression in small intestinal biopsies

    Time frame: 4 weeks

    measured by RNA sequencing

  6. Changes in Fecal microbiota composition

    Time frame: 4 weeks

    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

  7. Changes in abundance of post prandial plasma metabolites

    Time frame: 4 weeks

    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

Study contacts

Contact information is provided by the study sponsor or research team.

Max Nieuwdorp, Prof

CONTACT

[email protected]

0031 20 5669111

Sponsors and collaborators

Lead sponsor

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

Other

Registry information

Official study title

Luminal Fructose Kinetics (MARTINI) (2024)

Acronym: MARTINI

Important dates

Study start
2024
Primary completion
2026
Study completion
2026
First posted
Aug 6, 2024
Registry last updated
Aug 6, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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