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The Effect of Probiotics on E. Coli-induced Gastroenteritis (PROTETEC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01709266
Recruitment Status : Completed
First Posted : October 18, 2012
Last Update Posted : August 27, 2015
Sponsor:
Collaborator:
Lallemand Health Solutions
Information provided by (Responsible Party):
NIZO Food Research

Study Description
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Brief Summary:

Background:

The incidence of gastrointestinal infections is very high. In Western countries at least 30% of the population suffers from at least one food-borne infection per year. Mostly because of the problem of antibiotic resistance, more emphasis is put on prevention of infections. One of the possibilities is to strengthen human resistance to gut infections by consumption of probiotics. A specific blend of probiotic lactic acid bacteria (Lactobacillus helveticus Rosell-52, Lactobacillus rhamnosus Rosell-11, Bifidobacterium longum Rosell-175) and a probiotic yeast (Saccharomyces boulardii), improved stool consistency and shortened the duration of diarrhea in a rat model of E.coli-induced diarrhea. These probiotics showed synergistic effects compared with administration of solely S. boulardii or a mixture of L. helveticus Rosell-52, L. rhamnosus Rosell-11, B. longum Rosell-175. Consumption of S. boulardii and a combination of L. helveticus Rosell-52, L. rhamnosus Rosell-11 reduced diarrhea in humans.

Aim:

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

Study design:

The PROTETEC study is a parallel, double-blind, placebo-controlled 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=30 per group). Subjects will be instructed to maintain their usual pattern of physical activity and 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 10E10 CFU). Before and after infection, a diary will be kept to record all food and drinks consumption (2x2 days) to assess the habitual dietary intake, as well as for daily recording of bowel habits and frequency and severity of gastrointestinal complaints. The following biological samples will be collected: 4x10 ml venous blood, a single fecal bolus (for screening) and 7x24 hrs feces. Blood is sampled for immune response analyses and the fecal 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 (capsules containing freeze-dried powder, probiotic dose per capsule 5x10E9 CFU; twice daily) or placebo (capsules with carrier material powder of identical appearance)

Primary outcomes:

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

Secondary outcomes:

Serum immune response to ETEC, self-reported stool consistency scores and gastrointestinal complaints, relative fecal wet weight.

Tertiary outcomes:

sIgA and calprotectin in feces, probiotic persistence and levels of opportunistic pathogens in the endogenous microbiota.


Condition or disease Intervention/treatment Phase
Gastroenteritis Bacterial Infection Diarrhea Dietary Supplement: Probiotics Dietary Supplement: Placebo Not Applicable

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Randomized, Placebo-controlled, Double Blind Volunteer Study Into the Effect of Probiotics on Gastroenteritis Caused by an Attenuated E. Coli.
Study Start Date : August 2012
Actual Primary Completion Date : November 2012
Actual Study Completion Date : November 2012

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Probiotics
Capsule containing 5x10E9 CFU probiotics. Twice daily for 2 weeks.
 Dietary Supplement: Probiotics
Placebo Comparator: Placebo
Capsule containing carrier material powder of identical appearance. Twice daily for 2 weeks.
 Dietary Supplement: Placebo


Outcome Measures
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Primary Outcome Measures :
  1. Fecal ETEC excretion curve over time as marker of the colonization resistance [ Time Frame: Fecal ETEC excretion measured 1-2 days before ETEC infection, and on day 1, 2, 3, 4, 7 and 15 after infection. ]
    The curve of fecal ETEC excretion over time is compared between verum and placebo group.

  2. Total daily fecal output curve over time as marker of diarrhea [ Time Frame: Daily fecal output is measured 1-2 days before ETEC infection (baseline), and on day 1, 2, 3, 4, 7 and 15 after infection. ]
    The curve of daily fecal output over time is compared between verum and placebo group.


Secondary Outcome Measures :
  1. Bowel habits [ Time Frame: Scored daily in a diary during 4 weeks, starting at the day of dietary intervention until 2 weeks after ETEC infection. ]
  2. Frequency and severity of gastrointestinal symptoms [ Time Frame: Scored daily by VAS scores in a diary during 4 weeks, starting at the day of dietary intervention until 2 weeks after ETEC infection. ]
  3. Diarrhea severity [ Time Frame: 1-2 days before ETEC infection, and on day 1, 2, 3, 4, 7 and 15 after infection. ]
    Measured by fecal dry weight excretion and % fecal dry weight.

  4. Specific serum antibody response to CFA-II [ Time Frame: Before and at day 3 and 15 after ETEC infection. ]

Other Outcome Measures:
  1. Opportunistic pathogens in feces [ Time Frame: 1-2 days before ETEC infection, and on selected time points after infection (day 1, 2, 3, 4, 7 or 15, depending on results of primary and secondary outcomes). ]
    Measurement of tertiary study outcomes will depend on the results of the primary and secondary study outcomes.

  2. Calprotectin in feces [ Time Frame: 1-2 days before ETEC infection, and on selected time points after infection (day 1, 2, 3, 4, 7 or 15, depending on results of primary and secondary outcomes). ]
    Measurement of tertiary study outcomes will depend on the results of the primary and secondary study outcomes.

  3. Total faecal sIgA [ Time Frame: 1-2 days before ETEC infection, and on seleceted time points after infection (day 1, 2, 3, 4, 7 or 15, depending on results of primary and secondary outcomes). ]
    Measurement of tertiary study outcomes will depend on the results of the primary and secondary study outcomes.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Signed informed consent
  • Male
  • Age 20-55 yrs
  • Availability of internet connection
  • Willingness to replace habitual dairy product intake with the supplied low-calcium soy products
  • Willingness to abstain from products with high amounts of prebiotic fibers and from products with probiotics (except for the supplied one) starting 1 month prior to study start
  • Willingness to give blood donation from 1 month before the start of the experiment and during the entire experimental period.

Exclusion Criteria:

  • Current or previous underlying disease of the GI tract, liver, bile bladder, kidney, thyroid gland (self-reported)
  • Allergy to milk products or lactose intolerance (self-reported), since the capsules may contain milk traces from culture media
  • Allergy to soy products (self-reported)
  • Use of antibiotics, norit, laxatives (up till 6 months prior to inclusion), cholestyramine, acid burn inhibitors or immune suppressive agents (up till 3 months prior to inclusion), and pre- and probiotics (up till 1 month prior to inclusion).
  • High titer serum antibodies against ETEC (10 ml blood sample collected at screening)
  • Vegetarians
  • Vegans
  • Heavy alcohol use (>4 consumptions/day or >20/week)
  • Drug use
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01709266


Locations
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Netherlands
NIZO Food Research
Ede, Utrecht, Netherlands, 6718 ZB
Sponsors and Collaborators
NIZO Food Research
Lallemand Health Solutions
More Information
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Publications of Results:

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Responsible Party: NIZO Food Research
ClinicalTrials.gov Identifier: NCT01709266    
Other Study ID Numbers: NL40301.081.12
First Posted: October 18, 2012    Key Record Dates
Last Update Posted: August 27, 2015
Last Verified: August 2015
Additional relevant MeSH terms:
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Bacterial Infections
Gastroenteritis
Diarrhea
Signs and Symptoms, Digestive
 Bacterial Infections and Mycoses
Infections
Gastrointestinal Diseases
Digestive System Diseases