Effect of Proton Pump Inhibitors on the Duodenal Microbiome in Healthy Volunteers and Functional Dyspepsia Patients
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 79
- 试验地点
- 1
- 主要终点
- Change in microbiota composition
研究概览
简要总结
Prospective interventional study of the effect of PPI on the duodenal microbiome in healthy volunteers and functional dyspepsia patients
详细描述
PPIs are the first-line therapy in functional dyspepsia (FD) but frequently (over-)prescribed with potential adverse events, especially in the long term. As C. difficile and CAP are important causes of morbidity, mortality and healthcare costs, it is important to study the underlying mechanisms of PPI-induced dysbiosis.
In this prospective interventional study, study procedures will be performed at inclusion (1), after a baseline period of 4 weeks (2) and after treatment with Pantoprazole (Pantomed®) 40mg once daily during 4 weeks (3) in healthy volunteers and FD patients. In addition, study procedures will be performed at inclusion (1) and after PPI-withdrawal for 8 weeks in refractory FD patients.
The investigators aim to assess alterations of the duodenal (mucosa-associated and luminal) microbiome with PPI therapy and to correlate changes in the duodenal microbiota with oral and fecal microbiota, bile acids, intestinal permeability and histology and biochemical variables.
The results from this study will help to unravel the onset and extent of dysbiosis and provide additional arguments not to prescribe or continue PPI without clear clinical indications, especially in cases where alternative regimens may be available or the benefits of PPI are uncertain.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subjects aged between 18 and 64 years inclusive
- •Male or female (not pregnant or lactating and using contraception or postmenopausal)
- •Normal bowel habits (defecation once every 3 days up to 3 times a day)
- •Witnessed written informed consent
- •Access to home freezer (-18 to -20°C)
- •Capable to understand and comply with the study requirements
排除标准
- •Active psychiatric symptoms (stable dose of single antidepressant allowed)
- •Use of acid suppressive drugs (before starting Pantomed), immunosuppressants or antibiotics <3 months before sampling
- •Use of drugs influencing stool consistency, NSAIDs, anti-allergy drugs, bile acid sequestrants or ursodeoxycholic acid <2 weeks before sampling
- •Use of prokinetics <2 weeks before sampling (unless if ≤3/week)
- •History of major abdominal surgery, including cholecystectomy but not appendectomy or splenectomy
- •Personal or family (first-degree relative) history of diabetes mellitus type 1, celiac disease, inflammatory bowel disease, psoriasis, rheumatic or other auto-immune diseases (including therapy)
- •Allergy or atopy (eczema, asthma and/or allergic rhinoconjunctivitis) (including therapy)
- •Kidney, liver or coagulation disorders
- •Active coronary or peripheral artery disease
- •Diabetes mellitus type 2 (including therapy)
- •Active malignancy (including therapy)
- •Known HIV, HBV or HCV infection (including therapy)
- •Magnetizable objects (e.g. cochlear implants, neural stimulator, pacemaker, metal fragments or implants) or claustrophobia (MRI safety criteria with additional consent form, other procedures can still take place)
- •Significant alcohol use (>10 units/weeks)
- •Any use of alcohol or smoking ≤2 days before sampling
- •Females who are pregnant or lactating, who are not using contraception and premenopausal
研究组 & 干预措施
Pantoprazole 40mg in healthy volunteers
Peroral Pantoprazole 40mg once daily for 4 weeks
干预措施: Pantoprazole 40mg (Drug)
Pantoprazole 40mg in functional dyspepsia
Peroral Pantoprazole 40mg once daily for 4 weeks
干预措施: Pantoprazole 40mg (Drug)
PPI-withdrawal in functional dyspepsia
no PPI for 8 weeks
干预措施: PPI withdrawal (Other)
结局指标
主要结局
Change in microbiota composition
时间窗: 4 weeks
Change in microbiota composition in the duodenum (lumen and mucosa) and feces
次要结局
- Change in mucosal permeability(4 weeks)
- Change in bile acid composition(4 weeks)
- Change in mucosal inflammation(4 weeks)