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

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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

Tracking Information
First Submitted Date  ICMJE October 11, 2012
First Posted Date  ICMJE October 18, 2012
Last Update Posted Date August 27, 2015
Study Start Date  ICMJE August 2012
Actual Primary Completion Date November 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 16, 2012)
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01709266 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 16, 2012)
  • 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. ]
  • 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. ]
  • 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.
  • Specific serum antibody response to CFA-II [ Time Frame: Before and at day 3 and 15 after ETEC infection. ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: October 16, 2012)
  • 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.
  • 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.
  • 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.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE The Effect of Probiotics on E. Coli-induced Gastroenteritis
Official Title  ICMJE A Randomized, Placebo-controlled, Double Blind Volunteer Study Into the Effect of Probiotics on Gastroenteritis Caused by an Attenuated E. Coli.
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE
  • Gastroenteritis
  • Bacterial Infection
  • Diarrhea
Intervention  ICMJE
  • Dietary Supplement: Probiotics
  • Dietary Supplement: Placebo
Study Arms  ICMJE
  • Experimental: Probiotics
    Capsule containing 5x10E9 CFU probiotics. Twice daily for 2 weeks.
    Intervention: Dietary Supplement: Probiotics
  • Placebo Comparator: Placebo
    Capsule containing carrier material powder of identical appearance. Twice daily for 2 weeks.
    Intervention: Dietary Supplement: Placebo
Publications * Ten Bruggencate SJ, Girard SA, Floris-Vollenbroek EG, Bhardwaj R, Tompkins TA. The effect of a multi-strain probiotic on the resistance toward Escherichia coli challenge in a randomized, placebo-controlled, double-blind intervention study. Eur J Clin Nutr. 2015 Mar;69(3):385-91. doi: 10.1038/ejcn.2014.238. Epub 2014 Nov 5.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 16, 2012)
60
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE November 2012
Actual Primary Completion Date November 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 20 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01709266
Other Study ID Numbers  ICMJE NL40301.081.12
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party NIZO Food Research
Study Sponsor  ICMJE NIZO Food Research
Collaborators  ICMJE Lallemand Health Solutions
Investigators  ICMJE Not Provided
PRS Account NIZO Food Research
Verification Date August 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP