Luminal Fructose Kinetics (MARTINI Study)

NCT06539494 | Recruiting Phase 2 DMC

• 1 other identifier: NL85966.018.23
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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.

Conditions

MASLD

Keywords

Fructose; MASLD; Ethanol

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (7)

• Changes in microbiota composition in luminal samples

  four weeks

• Changes in dietary intake

  four weeks

• Bioreactor analyses

  four weeks

• Changes in Oral microbiota composition

  four weeks

• Differences in gene expression in small intestinal biopsies

  4 weeks

Study Arms (2)

Healthy volunteer

ACTIVE COMPARATOR

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

Drug: Omeprazole 40 MG

Sujbects with MASLD

ACTIVE COMPARATOR

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

Drug: Omeprazole 40 MG

Interventions

Omeprazole 40 MG DRUG

Proton pump inhibitor twice a day for 4 weeks

Healthy volunteer; Sujbects with MASLD

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead

Study Sites (1)

Amsterdam UMC location AMC

Amsterdam, Netherlands

RECRUITING

MeSH Terms

Interventions

Omeprazole

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Max Nieuwdorp, prof

  Amsterdam UMC, location AMC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Max Nieuwdorp, Prof

CONTACT

0031 20 5669111; m.nieuwdorp@amsterdamumc.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Model Details: 2x 11 participants will be given the same intervention (omeprazol daily)

Study Record Dates

• First Submitted: July 18, 2024
• First Posted: August 6, 2024
• Study Start: July 1, 2024
• Primary Completion: January 1, 2026
• Study Completion: April 1, 2026
• Last Updated: August 6, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)