The Effect of Probiotics on E. Coli Gastroenteritis (PRETEC)

This study has been completed.
Sponsor:
Collaborator:
Danisco
Information provided by (Responsible Party):
NIZO Food Research
ClinicalTrials.gov Identifier:
NCT01225042
First received: October 15, 2010
Last updated: October 2, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention
Gastroenteritis
Bacterial Infection
Diarrhea
Dietary Supplement: probiotics
Dietary Supplement: placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: The Effect of Probiotics on E. Coli Gastroenteritis

Resource links provided by NLM:


Further study details as provided by NIZO Food Research:

Primary Outcome Measures:
  • Total daily faecal ETEC excretion with time [ Time Frame: 1-2 days before ETEC infection and on days 1, 2, 3, 5 and 15 after ETEC infection ] [ Designated as safety issue: No ]
  • Total daily faecal output with time [ Time Frame: 1-2 days before ETEC infection and on days 1, 2, 3, 5, 15 after ETEC infection ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Bowel habits [ Time Frame: Scored daily in a diary ] [ Designated as safety issue: No ]
  • Frequency and severity of gastrointestinal symptoms [ Time Frame: Scored daily by VAS scales in a diary ] [ Designated as safety issue: No ]
  • Diarrhea severity [ Time Frame: 1-2 days before ETEC infection and on days 1, 2, 3, 5, and 15 after ETEC infection ] [ Designated as safety issue: No ]
    Determined as % faecal wet weight

  • Opportunistic pathogens in faeces [ Time Frame: At a single day just before ETEC infection and at a single time point in the first week after ETEC infection ] [ Designated as safety issue: No ]
  • Faecal calprotectin [ Time Frame: 1-2 days before ETEC infection and on days 1, 2, 3, 5, and 15 after ETEC infection ] [ Designated as safety issue: No ]
  • Serum antibody response to CFA II [ Time Frame: At screening (baseline) and at days 9 and 15 after ETEC infection ] [ Designated as safety issue: No ]
  • Total faecal sIgA [ Time Frame: 1-2 days before ETEC infection and on days 1, 2, 3, 5, and 15 after ETEC infection ] [ Designated as safety issue: No ]

Enrollment: 40
Study Start Date: October 2010
Study Completion Date: April 2011
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: probiotics
Freeze-dried powder, dose 10E9 CFU twice daily for 4 weeks
Dietary Supplement: probiotics
Freeze-dried powder, dose 10E9 CFU twice daily for 4 weeks
Other Name: probiotics
Placebo Comparator: placebo
Carrier material powder of identical appearance
Dietary Supplement: placebo
placebo consisting of carrier material powder of identical appearance
Other Name: placebo

Detailed Description:

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

  Eligibility

Ages Eligible for Study:   20 Years to 55 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01225042

Locations
Netherlands
NIZO food research
Ede, Netherlands, 6718 ZB
Sponsors and Collaborators
NIZO Food Research
Danisco
Investigators
Principal Investigator: Ingeborg Bovee-Oudenhoven, PhD NIZO Food Research
Principal Investigator: Sandra ten Bruggencate, PhD NIZO Food Research
Principal Investigator: Arthur Ouwehand, PhD Danisco Finland
  More Information

No publications provided

Responsible Party: NIZO Food Research
ClinicalTrials.gov Identifier: NCT01225042     History of Changes
Other Study ID Numbers: NIZO_PRETEC_2010
Study First Received: October 15, 2010
Last Updated: October 2, 2012
Health Authority: Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by NIZO Food Research:
infectious diarrhea
probiotics
prevention
dietary intervention
E. coli infection
intestinal infection
intestinal resistance

Additional relevant MeSH terms:
Bacterial Infections
Diarrhea
Gastroenteritis
Signs and Symptoms, Digestive
Signs and Symptoms
Gastrointestinal Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on April 15, 2014