Gastroenteritis Traveler's diarrhea
Conditions
Interventions
A live attenuated diarrheagenic E. coli strain (strain E1392/75-2A
collectie
NIZO food research). Five groups of 6 subjects will be provided one of the
following dosages: 1*10^10 CFU (standard dose)
1*10^9 CFU
1*10^8 CFU
1*10^7
CFU
1*10^6 CFU. At study day 35, after a standardized evening meal and an
overnight fast, all subjects will receive a second inoculation of 1*10^10 CFU
of the E.coli strain (n=30).
Sponsors
NIZO food research BV
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Male 2. Age between 18 and 55 years. 3. BMI *18.5 and *30.0 kg/m2. 4. Healthy as assessed by the NIZO food research medical questionnaire.
Exclusion criteria
Exclusion criteria: 1. Acute gastroenteritis in the 2 months prior to inclusion 2. Any confirmed or suspected immunosuppressive or immunodeficient condition including human immunodeficiency virus infection (HIV). 3. Disease of the GI tract, liver, gall bladder, kidney, thyroid gland (self-reported), except for appendicitis. 4. History of microbiologically confirmed ETEC or cholera infection within 3 years prior to inclusion. 5. Symptoms consistent with Travelers' Diarrhea concurrent with travel to countries where ETEC infection is endemic (most of the developing world) within 3 years prior to inclusion, OR planned travel to endemic countries during the length of the study. 6. Vaccination for, or ingestion of cholera, including studies at NIZO, within 3 years prior to inclusion. 7. Occupation involving handling of ETEC or Vibrio cholerae currently, or within 3 years prior to inclusion. 8. Vaccination for, or ingestion of ETEC or E coli heat labile toxin, including E. coli challenge studies at NIZO. 9. Evidence of current excessive alcohol consumption (>4 consumptions/day or >20 consumptions/week) or drug (ab)use, and not willing/able to stop this during the study. 10. Known allergy to the following antibiotics: ciprofloxacin, trimethoprim-sulfamethoxazole, and penicillins. 11. Reported average stool frequency of >3 per day or
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main study parameter: * Specific antibody titer, serum IgG-CFA/II antibody levels at second E. coli inoculation. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary study parameters: * Relative and total fecal wet weight (Freeze-drying of pooled 24 h fecal samples) at first and second E. coli inoculation * Stool consistency (Bristol Stool Scale reported by the subjects in the online diary) at first and second E. coli inoculation * Stool frequency (Stools per day reported by the subjects in the online diary) at first and second E. coli inoculation * Incidence, duration and severity of Gastro-intestinal symptoms (Gastro-intestinal Symptom Rating Scale reported by the subjects in the online diary) at first and second E. coli inoculation Tertiary exploratory study parameters: * Functional immunological assays in peripheral blood mononuclear cells (response to TLR stimulation, phagocytosis, neutrophil function) * Additional ELISA determinations to identify the response to infection (in plasma) * Measurement of barrier/inflammation markers in fecal samples The primary and secondary outcomes are aimed to obtain more insight into the clinical response to infection at five primary E. coli dosages, and the impact on the protective response at secondary infection. This dose-response information will help to establish the optimal design for a subsequent well-powered intervention study, aimed at support of the protective response at secondary infection. The exploratory study parameters will help to identify additional correlates of protection against reinfection. | — |
Countries
Netherlands
Outcome results
None listed