Luminal Fructose Kinetics (MARTINI Study) (MARTINI)

Luminal Fructose Kinetics (MARTINI) (2024)

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.

Study Overview

• Status: Recruiting
• Conditions: MASLD
• Intervention / Treatment: Drug: Omeprazole 40 MG

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.

• Study Type: Interventional
• Enrollment (Estimated): 22
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Max Nieuwdorp, Prof; Phone Number: 0031 20 5669111; Email: m.nieuwdorp@amsterdamumc.nl

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • Recruiting
    • Amsterdam UMC location AMC
    • Contact: max nieuwdorp, MD PhD; Phone Number: 0031 20 5669111; Email: m.nieuwdorp@amsterdamumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Healthy volunteer; healthy volunteers who will get omeprazol daily 2dd40 mg for 4 weeks	Drug: Omeprazole 40 MG; Proton pump inhibitor twice a day for 4 weeks
Active Comparator: Sujbects with MASLD; Patients with MASLD who will get omeprazol daily 2dd40 mg for 4 weeks	Drug: Omeprazole 40 MG; Proton pump inhibitor twice a day for 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Investigators: Principal Investigator: Max Nieuwdorp, prof, Amsterdam UMC, location AMC

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2024
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: July 18, 2024
• First Submitted That Met QC Criteria: August 1, 2024
• First Posted (Actual): August 6, 2024

Study Record Updates

• Last Update Posted (Actual): August 6, 2024
• Last Update Submitted That Met QC Criteria: August 1, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Ethanol; Fructose; MASLD
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Omeprazole
• Other Study ID Numbers: NL85966.018.23

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No