Clinical trial NCT01225042: The Effect of Probiotics on E. Coli Gastroenteritis
Official title: The Effect of Probiotics on E. Coli Gastroenteritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Gastroenteritis
Bacterial Infection
Diarrhea
Keywords: infectious diarrhea
probiotics
prevention
dietary intervention
E. coli infection
intestinal infection
intestinal resistance
Lead sponsor: NIZO Food Research
Sponsor class: OTHER
Collaborators: name: Danisco
First posted: 2010-10-20
Enrollment: 40
Sex: MALE
Minimum age (years): 20
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Background:

The incidence of gastrointestinal infections is very high. In European countries 10-25% of the population suffers from at least one foodborne infection per year. Probiotics may strengthen human resistance to gut infections as they may beneficially modulate the intestinal microbiota composition and activity, and the immune function upon intestinal infection.

Aim:

To study whether probiotics improve the resistance of humans to enterotoxigenic E. coli (ETEC).

Study design:

The PRETEC study is a parallel, double-blind, placebo-controled 4-weeks intervention with probiotics in healthy volunteers. In this study, the effect of probiotic intervention vs placebo on several infection markers in response to an ETEC challenge is investigated. Participants will be randomly assigned to the probiotic or placebo group (n=21 per group). Subjects will be instructed to maintain their habitual food intake, but to standardize their dietary calcium intake. After an adaptation period of 2 weeks, subjects will be orally infected with a live, but attenuated, ETEC vaccine (strain E1392-75-2A; collection NIZO food research; dose will be 10E10 CFU). This ETEC strain induces mild and short-lived infectious diarrhea symptoms. Before and after infection, a diary will be kept to write down all food and drinks consumption (2x2 days) to assess the habitual dietary intake. The diary will also be used for daily recording of bowel habits and frequency and severity of gastrointestinal complaints. Blood is sampled for immune response analyses and multiple faecal samples are collected to quantify several infection- and immune system markers, to determine probiotic excretion, and to verify dietary calcium intake.

Study population:

Healthy males of 20-55 yrs of age.

Interventions:

Probiotics (freeze-dried powder, dose 10E9 CFU twice daily) or placebo (carrier material powder of identical appearance).

Primary outcomes:

Total fecal ETEC excretion per day and severity of diarrhea (quantified by faecal output per day).

Secondary outcomes:

Serum immune response to ETEC, self-reported stool consistency scores and gastrointestinal complaints, relative faecal wet weight, sIgA and calprotectin in faeces, probiotic persistence and levels of opportunistic pathogens in the endogenous microbiota.

Detailed description: The timeframes for analysis of the primary and secondary outcomes is mentioned below in the Outcome Measures section.

Eligibility criteria: Inclusion Criteria:

* Signed informed consent
* Male
* Age 20-55 yrs
* Willingness to replace habitual dairy product intake with the supplied low- calcium soy milk products
* Willingness to abstain from products with high amounts of prebiotic fibers and products with probiotics (except for the supplied one)

Exclusion Criteria:

* Current or previous underlying disease of the GI tract
* lactose intolerance
* Use of antibiotics, norit, laxatives, cholestyramine, acid burn inhibitors, immune suppressiva, prebiotics, probiotics
* detectable serum antibodies against ETEC
* carriage of streptomycin-resistant E. coli in faeces (only relevant when culturing technique for ETEC will be applied instead of specific RT-PCR)
* vegetarians
* heavy alcohol use
* drug use

Primary outcomes:
measure: Total daily faecal ETEC excretion with time
timeFrame: 1-2 days before ETEC infection and on days 1, 2, 3, 5 and 15 after ETEC infection
measure: Total daily faecal output with time
timeFrame: 1-2 days before ETEC infection and on days 1, 2, 3, 5, 15 after ETEC infection
Secondary outcomes:
measure: Bowel habits
timeFrame: Scored daily in a diary
measure: Frequency and severity of gastrointestinal symptoms
timeFrame: Scored daily by VAS scales in a diary
measure: Diarrhea severity
timeFrame: 1-2 days before ETEC infection and on days 1, 2, 3, 5, and 15 after ETEC infection
measure: Opportunistic pathogens in faeces
timeFrame: At a single day just before ETEC infection and at a single time point in the first week after ETEC infection
measure: Faecal calprotectin
timeFrame: 1-2 days before ETEC infection and on days 1, 2, 3, 5, and 15 after ETEC infection
measure: Serum antibody response to CFA II
timeFrame: At screening (baseline) and at days 9 and 15 after ETEC infection
measure: Total faecal sIgA
timeFrame: 1-2 days before ETEC infection and on days 1, 2, 3, 5, and 15 after ETEC infection
Other outcomes:
Locations:
city: Ede
country: Netherlands
facility: NIZO food research
Study officials:
affiliation: NIZO Food Research
name: Ingeborg Bovee-Oudenhoven, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: NIZO Food Research
name: Sandra ten Bruggencate, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Danisco Finland
name: Arthur Ouwehand, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ouwehand AC, ten Bruggencate SJ, Schonewille AJ, Alhoniemi E, Forssten SD, Bovee-Oudenhoven IM. Lactobacillus acidophilus supplementation in human subjects and their resistance to enterotoxigenic Escherichia coli infection. Br J Nutr. 2014 Feb;111(3):465-73. doi: 10.1017/S0007114513002547. Epub 2013 Aug 12.