The Role of the Microbiota in the Systemic Immune Response
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Composite measure of Laboratory parameters for inflammatory responses.
研究概览
简要总结
The objective of this study is to investigate the role of the gut microbiota in the systemic priming of immune effector cells. Twelve healthy male volunteers, 18-35 years of age, will be treated with broad spectrum antibiotics (ciprofloxacin, vancomycin, metronidazole) for seven days, in order to deplete the gut microbiota. Blood and faeces will be sampled before, 24 hours and 6 weeks after the 7-day period of antibiotics. Main study endpoints include laboratory parameters for inflammatory responses, functional assays (ex vivo stimulation assay) and gut microbiota composition.
详细描述
Rationale: Sepsis ranks among the top ten leading causes of death worldwide. Most nonsurvivors die in a state of immunosuppression. The gut microbiota exerts numerous beneficial functions in the host response against infections. Gut flora components express microorganism-associated molecular patterns (MAMPs) such as lipopolysaccharide (LPS), which are recognized by pattern recognition receptors (PRRs) expressed by neutrophils and macrophages. MAMPs from the intestinal microbiota constitutively translocate to the circulation and prime bone marrow derived neutrophils via PRRs. Antibiotic treatment, which is standard of care for all patients with sepsis, depletes the gut microbiota and leads to a diminished release of MAMPs and other bacteria derived products. This causes diminished priming of systemic immunity, which may attribute to sepsis associated immunosuppression and an increased susceptibility to invading bacteria.
Objective: To investigate the role of the gut microbiota in the systemic priming of immune effector cells
Study design: Within-subject-controlled intervention study in human volunteers
Study population: Twelve healthy male subjects, 18-35 years of age
Intervention: All subjects will be treated with broad spectrum antibiotics (ciprofloxacin, vancomycin, metronidazole) for seven days, in order to deplete the gut microbiota. Blood and faeces will be sampled before, 24 hours and 6 weeks after the 7-day period of antibiotics.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Male between 18 and 35 years of age
- •Capable of giving written informed consent and able to comply with the requirements and restrictions
- •Chemistry panel without any clinically relevant abnormality
- •Normal defecation pattern (defined as <3x/ day and >3x/week)
排除标准
- •Major illness in the past 3 months or significant chronic medical illness;
- •History of any type of malignancy;
- •Past or current gastrointestinal disease which may influence the gut microbiota;
- •Known positive test for hepatitis C antibody, hepatitis B surface antigen or HIV;
- •Current or chronic history of liver disease, or known hepatic or biliary abnormalities;
- •Use of tobacco products;
- •History, within 3 years, of drug abuse;
- •History of alcoholism and/or drinking more than 3 units of alcohol per day;
- •The subject has received an investigational product within three months of day 1;
- •Use of prescription or non-prescription drugs and herbal and dietary supplements within 6 months;
- •Recent (< 12 months) use of antibiotics (any kind, except for dermal antibiotics);
- •Allergy to antibiotics (any kind);
- •Difficulty swallowing pills;
- •Any other relevant issue.
研究组 & 干预措施
Antibiotics
All volunteers will self-administer the following antibiotics for 7 consecutive days (concomitantly):
- Vancomycin 250mg 3dd2;
- Ciprofloxacin 500mg 2dd1;
- Metronidazole 500mg 3dd1.
干预措施: Vancomycin (Drug)
Antibiotics
All volunteers will self-administer the following antibiotics for 7 consecutive days (concomitantly):
- Vancomycin 250mg 3dd2;
- Ciprofloxacin 500mg 2dd1;
- Metronidazole 500mg 3dd1.
干预措施: Ciprofloxacin (Drug)
Antibiotics
All volunteers will self-administer the following antibiotics for 7 consecutive days (concomitantly):
- Vancomycin 250mg 3dd2;
- Ciprofloxacin 500mg 2dd1;
- Metronidazole 500mg 3dd1.
干预措施: Metronidazole (Drug)
结局指标
主要结局
Composite measure of Laboratory parameters for inflammatory responses.
时间窗: up to 7 weeks
Ex vivo response of whole blood, isolated monocytes or neutrophils to lipopolysaccharide.
次要结局
未报告次要终点
研究者
W.J. Wiersinga, MD, PhD
MD, PhD
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)