GastroenteritisPROTETECNCT01709266
The Effect of Probiotics on E. Coli-induced Gastroenteritis
A study testing Probiotics in people with Gastroenteritis and Bacterial Infection, run by NIZO Food Research at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 55 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Gastroenteritis, Bacterial Infection, Diarrhea
- What is being tested?
- Probiotics
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteNetherlands
- Study dates
- Aug 2012to Nov 2012
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 55 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 9Show fewer
- Vegans
- Heavy alcohol use (>4 consumptions/day or >20/week)
- Drug use
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Placebo-controlled, Double Blind Volunteer Study Into the Effect of Probiotics on Gastroenteritis Caused by an Attenuated E. Coli.
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.
Read more
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.
- Conditions
- Gastroenteritis, Bacterial Infection, Diarrhea
- Being tested
- Probiotics, Placebo
- Medical subject headings
- Gastroenteritis, Bacterial Infections, Diarrhea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ProbioticsDietary supplement
PlaceboDietary supplement
| Study group | Role | What they receive |
|---|---|---|
| Probiotics | Experimental | Capsule containing 5x10E9 CFU probiotics. Twice daily for 2 weeks. Receives: Dietary Supplement: Probiotics |
| Placebo | Placebo comparator | Capsule containing carrier material powder of identical appearance. Twice daily for 2 weeks. Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fecal ETEC excretion curve over time as marker of the colonization resistance
The curve of fecal ETEC excretion over time is compared between verum and placebo group.
Measured: Fecal ETEC excretion measured 1-2 days before ETEC infection, and on day 1, 2, 3, 4, 7 and 15 after infection.
Total daily fecal output curve over time as marker of diarrhea
The curve of daily fecal output over time is compared between verum and placebo group.
Measured: Daily fecal output is measured 1-2 days before ETEC infection (baseline), and on day 1, 2, 3, 4, 7 and 15 after infection.
Secondary outcomes (4)
Bowel habits
Measured: 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
Measured: 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
Measured by fecal dry weight excretion and % fecal dry weight.
Measured: 1-2 days before ETEC infection, and on day 1, 2, 3, 4, 7 and 15 after infection.
Specific serum antibody response to CFA-II
Measured: Before and at day 3 and 15 after ETEC infection.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2012 (estimated)
- Study startAug 2012
- Primary completionNov 2012
- Study completionNov 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for GastroenteritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- NIZO Food Research
- Sponsor type
- University, hospital or other
- Collaborators
- Lallemand Health Solutions
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01709266
- Sponsor's protocol ID
- NL40301.081.12
- Acronym
- PROTETEC
- Status last verified
- Aug 2015
- First submitted
- 11 Oct 2012
- Last updated
- 27 Aug 2015
- Results posted
- No
- Data monitoring committee
- No
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.
PubMed 25369827
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Placebo-controlled, Double Blind Volunteer Study Into the Effect of Probiotics on Gastroenteritis Caused by an Attenuated E. Coli.
- ClinicalTrials.gov ID
- NCT01709266
- Acronym / sponsor ID
- PROTETEC / NL40301.081.12
- Conditions
- Gastroenteritis, Bacterial Infection, Diarrhea
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- NIZO Food ResearchUniversity, hospital or other
- Collaborators
- Lallemand Health Solutions
- Study start
- Aug 2012
- Primary completion
- Nov 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 18 Oct 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Probiotics | Experimental | Dietary Supplement: ProbioticsCapsule containing 5x10E9 CFU probiotics. Twice daily for 2 weeks. |
| Placebo | Placebo comparator | Dietary Supplement: PlaceboCapsule containing carrier material powder of identical appearance. Twice daily for 2 weeks. |
Who may qualify
- Ages
- 20 to 55 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (9 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Probiotics | Dietary supplement | Probiotics |
| Placebo | Dietary supplement | Placebo |
Primary outcome
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.
4 secondary outcomes
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.
Specific serum antibody response to CFA-II
Time frame: Before and at day 3 and 15 after ETEC infection.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2015.
- Results publication: PubMed 25369827Ten 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Probiotics in people with Gastroenteritis and Bacterial Infection, run by NIZO Food Research at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01709266, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2015.