The Effect of Probiotics on E. Coli Gastroenteritis

Diarrhea Clinical Trial

— PRETEC  

Official title:

The Effect of Probiotics on E. Coli Gastroenteritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01225042
• Other study ID #: N132716.081.10
• Status: Completed
• Phase: N/A
• First received: October 15, 2010
• Last updated: August 26, 2015
• Start date: October 2010
• Est. completion date: April 2011

Study information

• Verified date: August 2015
• Source: NIZO Food Research
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: April 2011
• Est. primary completion date: December 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 55 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Bacterial Infection
• Bacterial Infections
• Diarrhea
• Gastroenteritis

Intervention

Dietary Supplement:
• probiotics
Freeze-dried powder, dose 10E9 CFU twice daily for 4 weeks
• placebo
placebo consisting of carrier material powder of identical appearance

Locations

Country	Name	City	State
Netherlands	NIZO food research	Ede

Sponsors (2)

Lead Sponsor	Collaborator
NIZO Food Research	Danisco

Country where clinical trial is conducted

Netherlands, 

References & Publications (1)

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- — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total daily faecal ETEC excretion with time		1-2 days before ETEC infection and on days 1, 2, 3, 5 and 15 after ETEC infection	No
Primary	Total daily faecal output with time		1-2 days before ETEC infection and on days 1, 2, 3, 5, 15 after ETEC infection	No
Secondary	Bowel habits		Scored daily in a diary	No
Secondary	Frequency and severity of gastrointestinal symptoms		Scored daily by VAS scales in a diary	No
Secondary	Diarrhea severity	Determined as % faecal wet weight	1-2 days before ETEC infection and on days 1, 2, 3, 5, and 15 after ETEC infection	No
Secondary	Opportunistic pathogens in faeces		At a single day just before ETEC infection and at a single time point in the first week after ETEC infection	No
Secondary	Faecal calprotectin		1-2 days before ETEC infection and on days 1, 2, 3, 5, and 15 after ETEC infection	No
Secondary	Serum antibody response to CFA II		At screening (baseline) and at days 9 and 15 after ETEC infection	No
Secondary	Total faecal sIgA		1-2 days before ETEC infection and on days 1, 2, 3, 5, and 15 after ETEC infection	No