Luminal Fructose Kinetics (MARTINI) (2024)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Changes in ethanol concentrations before and after omeprazol usage
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •In case of the healthy subject group:
- •Adult individuals, age > 18 <65 years
- •Male or postmenopauzal females
- •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
排除标准
- •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
- •Blood thinners
- •Heart failure
研究组 & 干预措施
Healthy volunteer
healthy volunteers who will get omeprazol daily 2dd40 mg for 4 weeks
干预措施: Omeprazole 40 MG (Drug)
Sujbects with MASLD
Patients with MASLD who will get omeprazol daily 2dd40 mg for 4 weeks
干预措施: Omeprazole 40 MG (Drug)
结局指标
主要结局
Changes in ethanol concentrations before and after omeprazol usage
时间窗: four weeks
mM (serum, intestinal fluid, urine and feces)
Fructose metabolites in feces before and after omeprazol usage
时间窗: 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.
Fructose metabolites in urine
时间窗: 4 weeks
Using 24h urine, the investigators will measure fecal concentrations of fructose metabolites such as ethanol, as well as SCFAs and bile acids.
Changes in serum glucose concentrations before and after omeprazol
时间窗: 4 weeks
mmol/l measured during fructose challange test
Changes in fructose concentrations in peripheral blood before and after omeprazol usage
时间窗: 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
Changes in fructose metabolites in breath before and after omeprazol usage
时间窗: 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
次要结局
- Differences in gene expression in small intestinal biopsies(4 weeks)
- Changes in dietary intake(four weeks)
- Bioreactor analyses(four weeks)
- Changes in microbiota composition in luminal samples(four weeks)
- Changes in Oral microbiota composition(four weeks)
- Changes in Fecal microbiota composition(4 weeks)
- Changes in abundance of post prandial plasma metabolites(4 weeks)
研究者
Max Nieuwdorp
Principle Investigator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)