The Effect of Probiotics on E. Coli Gastroenteritis

NCT01225042 | Completed

• 1 other identifier: N132716.081.10
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Gastroenteritis; Bacterial Infection; Diarrhea

Keywords

infectious diarrhea; probiotics; prevention; dietary intervention; E. coli infection; intestinal infection; intestinal resistance

Outcome Measures

Primary Outcomes (2)

• 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

• Total daily faecal output with time

  1-2 days before ETEC infection and on days 1, 2, 3, 5, 15 after ETEC infection

Secondary Outcomes (7)

• Bowel habits

  Scored daily in a diary

• Frequency and severity of gastrointestinal symptoms

  Scored daily by VAS scales in a diary

• Diarrhea severity

  1-2 days before ETEC infection and on days 1, 2, 3, 5, and 15 after ETEC infection

• 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

• Faecal calprotectin

  1-2 days before ETEC infection and on days 1, 2, 3, 5, and 15 after ETEC infection

Study Arms (2)

probiotics

EXPERIMENTAL

Freeze-dried powder, dose 10E9 CFU twice daily for 4 weeks

Dietary Supplement: probiotics

placebo

PLACEBO COMPARATOR

Carrier material powder of identical appearance

Dietary Supplement: placebo

Interventions

probiotics DIETARY_SUPPLEMENT

Freeze-dried powder, dose 10E9 CFU twice daily for 4 weeks

probiotics

placebo DIETARY_SUPPLEMENT

placebo consisting of carrier material powder of identical appearance

placebo

Eligibility Criteria

• Age: 20 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• NIZO Food Research: lead
• Danisco: collaborator

Study Sites (1)

NIZO food research

Ede, 6718 ZB, Netherlands

Location

Related 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):465-73. doi: 10.1017/S0007114513002547. Epub 2013 Aug 12.

  PMID: 23930950 RESULT

MeSH Terms

Conditions

Gastroenteritis; Bacterial Infections; Diarrhea; Dysentery; Escherichia coli Infections

Interventions

Probiotics

Condition Hierarchy (Ancestors)

Gastrointestinal Diseases; Digestive System Diseases; Bacterial Infections and Mycoses; Infections; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Intestinal Diseases; Enterobacteriaceae Infections; Gram-Negative Bacterial Infections

Intervention Hierarchy (Ancestors)

Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Ingeborg Bovee-Oudenhoven, PhD

  NIZO Food Research

  PRINCIPAL INVESTIGATOR

• Sandra ten Bruggencate, PhD

  NIZO Food Research

  PRINCIPAL INVESTIGATOR

• Arthur Ouwehand, PhD

  Danisco Finland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2010
• First Posted: October 20, 2010
• Study Start: October 1, 2010
• Primary Completion: December 1, 2010
• Study Completion: April 1, 2011
• Last Updated: August 27, 2015

Record last verified: 2015-08

Locations

NL (1)