Ignite Creation Date:
2025-12-24 @ 1:20 PM
Ignite Modification Date:
2026-02-13 @ 8:44 AM
Study NCT ID:
NCT02541695
Status:
COMPLETED
Last Update Posted:
2017-01-13
First Post:
2015-08-31
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Characterization of Resistance Against Live-attenuated Diarrhoeagenic E. Coli
Sponsor:
NIZO Food Research
Organization:
Study Overview
Official Title:
Characterization Of Resistance Against Live-attenuated Diarrhoeagenic E. Coli
Status:
COMPLETED
Status Verified Date:
2017-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
CORAL
Brief Summary:
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.
Detailed Description:
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:
The CORAL study is a parallel 7-weeks intervention study. Subjects will be randomly assigned to one of two inoculation dosages of a live attenuated diarrhoeagenic E. coli (n=20 per group). Subjects will be instructed to maintain their usual pattern of physical activity and their habitual food intake, but to standardize their dietary calcium intake. After a standardized evening meal and an overnight fast, subjects will be orally infected with a live, but attenuated, diarrhoeagenic E. coli (strain E1392-75-2A; collection NIZO food research; dose will be either 1E10 CFU (n=22) or 5E10 CFU (n=22) at study day 14). At study day 35, after a standardized evening meal and an overnight fast, all subjects will receive a second inoculation of 1E10 CFU of the ETEC vaccine (n=44).
At various time points before and after both diarrhoeagenic E. coli challenges an online diary will be kept to record all food and drinks consumption to assess dietary macronutrient intake. Moreover, subjects will report information on stool consistency, frequency and severity of symptoms. At various time points before and after both diarrhoeagenic E. coli challenges venous blood and (complete) stool samples will be collected. Blood and fecal samples are collected to quantify several infection- and immune system markers.
Study population:
Healthy male subjects, 18-55 years of age who fulfil all of the inclusion criteria and none of the exclusion criteria will participate in the CORAL study.
Intervention:
At study day 14 and 35, after a standardized evening meal and an overnight fast, all subjects will receive an inoculation of the diarrhoeagenic E. coli (1E10 CFU (n=22) or 5E10 CFU (n=22) at study day 14; 1E10 CFU (n=40) at study day 35) Subjects will be instructed to maintain their habitual diet, except for their dairy intake. Dairy has a high calcium content and contributes significantly to total daily calcium intake. These dietary guidelines will limit calcium intake on average to 500 mg/day. From our previous studies, we know that calcium can significantly reduce the gastro-intestinal symptoms induced by the E. coli strain.
Main study parameter:
1\. Percentage of faecal dry weight (% determined by freeze-drying)
Secondary study parameters:
1. Total faecal wet weight (faecal weight in g/day)
2. Time to first diarrhoeal stool (reported by the subjects in the online diary)
3. Stool consistency (Bristol Stool Scale reported by the subjects in the online diary
4. Number of stools with Bristol Stool Scale \>4 (Bristol Stool Scale reported by the subjects in the online diary)
5. Stool frequency (Stools per day reported by the subjects in the online diary)
6. Incidence and duration of WHO-defined diarrhoea (Calculated from the Bristol Stool Scale and the Stool frequency reported by the subjects in the online diary)
7. The incidence, duration and severity of Gastro-intestinal symptoms (Gastro-intestinal Symptom Rating Scale reported by the subjects in the online diary).
8. In addition, the study contains an explorative phase consisting of biomarker and transcriptome analysis, in order to further explore and identify the mechanism and kinetics of the host response to the infection.
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:
The CORAL study is a parallel 7-weeks intervention study. Subjects will be randomly assigned to one of two inoculation dosages of a live attenuated diarrhoeagenic E. coli (n=20 per group). Subjects will be instructed to maintain their usual pattern of physical activity and their habitual food intake, but to standardize their dietary calcium intake. After a standardized evening meal and an overnight fast, subjects will be orally infected with a live, but attenuated, diarrhoeagenic E. coli (strain E1392-75-2A; collection NIZO food research; dose will be either 1E10 CFU (n=22) or 5E10 CFU (n=22) at study day 14). At study day 35, after a standardized evening meal and an overnight fast, all subjects will receive a second inoculation of 1E10 CFU of the ETEC vaccine (n=44).
At various time points before and after both diarrhoeagenic E. coli challenges an online diary will be kept to record all food and drinks consumption to assess dietary macronutrient intake. Moreover, subjects will report information on stool consistency, frequency and severity of symptoms. At various time points before and after both diarrhoeagenic E. coli challenges venous blood and (complete) stool samples will be collected. Blood and fecal samples are collected to quantify several infection- and immune system markers.
Study population:
Healthy male subjects, 18-55 years of age who fulfil all of the inclusion criteria and none of the exclusion criteria will participate in the CORAL study.
Intervention:
At study day 14 and 35, after a standardized evening meal and an overnight fast, all subjects will receive an inoculation of the diarrhoeagenic E. coli (1E10 CFU (n=22) or 5E10 CFU (n=22) at study day 14; 1E10 CFU (n=40) at study day 35) Subjects will be instructed to maintain their habitual diet, except for their dairy intake. Dairy has a high calcium content and contributes significantly to total daily calcium intake. These dietary guidelines will limit calcium intake on average to 500 mg/day. From our previous studies, we know that calcium can significantly reduce the gastro-intestinal symptoms induced by the E. coli strain.
Main study parameter:
1\. Percentage of faecal dry weight (% determined by freeze-drying)
Secondary study parameters:
1. Total faecal wet weight (faecal weight in g/day)
2. Time to first diarrhoeal stool (reported by the subjects in the online diary)
3. Stool consistency (Bristol Stool Scale reported by the subjects in the online diary
4. Number of stools with Bristol Stool Scale \>4 (Bristol Stool Scale reported by the subjects in the online diary)
5. Stool frequency (Stools per day reported by the subjects in the online diary)
6. Incidence and duration of WHO-defined diarrhoea (Calculated from the Bristol Stool Scale and the Stool frequency reported by the subjects in the online diary)
7. The incidence, duration and severity of Gastro-intestinal symptoms (Gastro-intestinal Symptom Rating Scale reported by the subjects in the online diary).
8. In addition, the study contains an explorative phase consisting of biomarker and transcriptome analysis, in order to further explore and identify the mechanism and kinetics of the host response to the infection.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: