Characterization Of Resistance Against Live-attenuated Diarrhoeagenic E. Coli
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 44
- 试验地点
- 3
- 主要终点
- Change in percentage of faecal dry weight from baseline
研究概览
简要总结
Although the existing diarrhoeagenic Escherichia coli (E. coli) challenge model is already suitable for dietary interventions in its current form, further characterization of the working-mechanism of the attenuated strain and further optimization of the study design will enable the investigators to better select those ingredients that affect the key pathophysiological processes. The aim of the CORAL study is to further characterize and increase the discriminative power of the diarrhoeagenic E. coli challenge model.
详细描述
Primary Objective:
In the CORAL study the investigators want to determine whether increasing the inoculation dose of diarrhoeagenic Escherichia coli (E. coli) to 5E10 Colony Forming Units (CFU) (at day 14) and addition of a second challenge 1E10 CFU (at day 35) will result in an increased effect-size and duration of measurable outcomes and in an expansion of the relevant clinical and biomarker readouts of the challenge model.
Secondary Objective:
By extensive biomarker and transcriptome analysis of blood and fecal samples, the investigators aim to explore the working mechanism of the non-toxin producing diarrhoeagenic E. coli strain and the kinetics of the host response to this infection. In addition, the investigators want to determine whether adding extended fasting and addition of a standardized evening meal, prior to the inoculation day, will result in a decreased between-subject variation.
Study design:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Ability to follow verbal and written instructions;
- •Age between 18 and 55 years;
- •Availability of internet connection;
- •BMI ≥20 and ≤27 kg/m2;
- •Healthy as assessed by the NIZO food research medical questionnaire;
- •Male subjects;
- •Signed informed consent;
- •Voluntary participation;
- •Willing to accept disclosure of the financial benefit of participation in the study to the authorities concerned;
- •Willing to accept use of all encoded data, including publication, and the confidential use and storage of all data for at least 15 years;
- •Willing to comply with study procedures;
- •Willingness to abstain from high calcium containing products.
- •Willingness to abstain from medications that contain acetaminophen, aspirin, ibuprofen, and other nonsteroidal anti-inflammatory drugs, (OTC) antacids and antimotility agents (eg, loperamide) on the three days before, during and 3 days after diarrhoeagenic E. coli challenge.
- •Willingness to abstain from alcoholic beverages three days before, during and three days after diarrhoeagenic E. coli challenge.
- •Willingness to give up blood donation starting 1 month prior to study start and during the entire study;
排除标准
- •Disease of the GI tract, liver, bile bladder, kidney, thyroid gland (self-reported);
- •Diarrhoeagenic E.coli strain (as used in the study) detected in fecal sample at screening;
- •Evidence of current excessive alcohol consumption or non-therapeutic drug (ab)use);
- •Evidence of IgA deficiency (serum IgA < 7 mg/dL or below the limit of detection of assay).
- •High titer serum antibodies against CFA-II diarrhoeagenic E.coli strain (as used in the study) at screening;
- •History of microbiologically confirmed ETEC or cholera infection in last 3 years.
- •Known allergy to the following antibiotics: ciprofloxacin, trimethoprim-sulfamethoxazole, and penicillins.
- •Mental status that is incompatible with the proper conduct of the study;
- •Not having a general practitioner, not allowing disclosure of participation to the general practitioner or not allow to inform the general practitioner about abnormal results.
- •Occupation involving handling of ETEC or Vibrio cholerae currently, or in the past 3 years.
- •Participation in any clinical trial including blood sampling and/or administration of substances starting 1 month prior to study start and during the entire study;
- •Personnel of NIZO food research, their partner and their first and second degree relatives;
- •Reported average stool frequency of <1 or >3 per day;
- •Symptoms consistent with Travelers' Diarrhoea concurrent with travel to countries where ETEC infection is endemic (most of the developing world) within 3 years prior to dosing, OR planned travel to endemic countries during the length of the study.
- •Use of antibiotics, norit, laxatives (up till 6 months prior to inclusion), cholestyramine, antacids H2 receptor antagonists or proton pump inhibitors or immune suppressive agents (up till 3 months prior to inclusion);
- •Vaccination for or ingestion of ETEC, cholera, or E coli heat labile toxin within 3 years prior to inclusion;
- •Vegetarians and vegans
结局指标
主要结局
Change in percentage of faecal dry weight from baseline
时间窗: Day 14-17 and Day 35-38
% of faecal dry weight determined by freeze-drying
次要结局
- Change in total faecal wet weight from baseline(Day 14-17 and Day 35-38)
- Time to first diarrhoeal stool(Day 14-15 and Day 35-36)
- Change in Stool frequency from baseline(Day 14-17 and Day 35-38)