Bacterial InfectionMIRAGENCT01800396
Milk Ingredients and Resistance Against E-coli-induced GastroEnteritis (MIRAGE)
A study testing Milk protein and Milk protein rich in phospholipids in people with Bacterial Infection and Diarrhea, 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 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Bacterial Infection, Diarrhea, Gastroenteritis
- What is being tested?
- Milk protein and Milk protein rich in phospholipids
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteNetherlands
- Study dates
- Feb 2013to May 2013
- 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 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Signed informed consent
- Age 18-55 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 starting 1 month prior to study start
- Willingness to give up 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)
- ETEC detected in fecal sample (collected at screening)
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- Vegetarians
- 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 Milk Ingredients 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 milk ingredients.
Aim: To study whether a milk protein concentrate rich in phospholipids improves the resistance of humans to enterotoxigenic E. coli (ETEC).
Read more
Study design: The MIRAGE study is a parallel, double-blind, placebo-controlled 4-weeks intervention with a milk protein concentrate rich in phospholipids in healthy subjects of 18-55 yrs of age. Participants will be randomly assigned to the milk protein concentrate rich in phospholipids 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 will be 1010 CFU). Before and after infection, an online diary will be kept to record 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.
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 and to verify dietary calcium intake. Saliva is sampled three times before and after infection to quantify immune system markers.
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.
- Conditions
- Bacterial Infection, Diarrhea, Gastroenteritis
- Being tested
- Milk protein, Milk protein rich in phospholipids
- Keywords
- Bacterial infection, Dairy, Diarrhea, Diet, E.Coli, Gastroenteritis, Milk, Stool consistency
- Medical subject headings
- Bacterial Infections, Diarrhea, Gastroenteritis, Escherichia coli Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Milk proteinDietary supplement
Milk protein rich in phospholipidsDietary supplement
| Study group | Role | What they receive |
|---|---|---|
| Milk protein | Placebo comparator | Milk powder, twice daily at breakfast and dinner. Receives: Dietary Supplement: Milk protein |
| Milk protein rich in phospholipids | Experimental | Milk powder, twice daily at breakfast and dinner. Receives: Dietary Supplement: Milk protein rich in phospholipids |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change of fecal ETEC numbers over time as a marker of intestinal colonization resistance
The change over time in fecal ETEC numbers is compared between treatment and placebo group.
Measured: Days -1 and -2 before ETEC challenge and days 1,2,3,4,7 and 15 after challenge
Change of total daily fecal output over time as a marker of infectious diarrhea
The change in the daily fecal output over time is compared between treatment and placebo group.
Measured: Days -1 and -2 before ETEC challenge and on days 1,2,3,4,7 and 15 after challenge.
Secondary outcomes (5)
Daily Bristol Stool Score as a marker for stool consistency
Measured: Days -1 and -2 before ETEC challenge and on days 1-15 after challenge.
Gastro-Intestinal Symptom Rating Scale (GSRS) for gastro-intestinal complaints
Measured: Days -1 and -2 before ETEC challenge and on days 1-15 after challenge
% fecal wet weight as a marker for Diarrhea severity
Measured: Days -1 and -2 before ETEC challenge and days 1-15 after challenge.
Stool frequency (number of stools per day)
Days -1 and -2 before ETEC challenge and on days 1-15 after challenge
Measured: Day -1 and -2 and days 0-15
Specific serum antibody response to CFAII
Measured: Before ETEC challenge and on day 15 after challenge.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2013 (estimated)
- Study startFeb 2013
- Primary completionMay 2013
- Study completionMay 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Bacterial InfectionStudies 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
- Arla Foods, Denmark
- Responsible party
- Sponsor
- Investigators
- Sandra Ten Bruggencate, PhD, Principal investigator, NIZO food research, The Netherlands
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01800396
- Sponsor's protocol ID
- NL41768.081.12
- Acronym
- MIRAGE
- Status last verified
- Aug 2015
- First submitted
- 21 Feb 2013
- Last updated
- 27 Aug 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Bovee-Oudenhoven IM, Lettink-Wissink ML, Van Doesburg W, Witteman BJ, Van Der Meer R. Diarrhea caused by enterotoxigenic Escherichia coli infection of humans is inhibited by dietary calcium. Gastroenterology. 2003 Aug;125(2):469-76. doi: 10.1016/s0016-5085(03)00884-9.
PubMed 12891550Ten Bruggencate SJ, Frederiksen PD, Pedersen SM, Floris-Vollenbroek EG, Lucas-van de Bos E, van Hoffen E, Wejse PL. Dietary Milk-Fat-Globule Membrane Affects Resistance to Diarrheagenic Escherichia coli in Healthy Adults in a Randomized, Placebo-Controlled, Double-Blind Study. J Nutr. 2016 Feb;146(2):249-55. doi: 10.3945/jn.115.214098. Epub 2015 Dec 23.
PubMed 26701793
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 Milk Ingredients on Gastroenteritis Caused by an Attenuated E.Coli.
- ClinicalTrials.gov ID
- NCT01800396
- Acronym / sponsor ID
- MIRAGE / NL41768.081.12
- Conditions
- Bacterial Infection, Diarrhea, Gastroenteritis
- Keywords
- Bacterial infection, Dairy, Diarrhea, Diet, E.Coli, Gastroenteritis, Milk, Stool consistency
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- NIZO Food ResearchUniversity, hospital or other
- Collaborators
- Arla Foods, Denmark
- Study start
- Feb 2013
- Primary completion
- May 2013 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 27 Feb 2013 (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 milk ingredients.
Aim: To study whether a milk protein concentrate rich in phospholipids improves the resistance of humans to enterotoxigenic E. coli (ETEC).
Study design: The MIRAGE study is a parallel, double-blind, placebo-controlled 4-weeks intervention with a milk protein concentrate rich in phospholipids in healthy subjects of 18-55 yrs of age. Participants will be randomly assigned to the milk protein concentrate rich in phospholipids 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 will be 1010 CFU). Before and after infection, an online diary will be kept to record 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.
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 and to verify dietary calcium intake. Saliva is sampled three times before and after infection to quantify immune system markers.
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.
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 |
|---|---|---|
| Milk protein | Placebo comparator | Dietary Supplement: Milk proteinMilk powder, twice daily at breakfast and dinner. |
| Milk protein rich in phospholipids | Experimental | Dietary Supplement: Milk protein rich in phospholipidsMilk powder, twice daily at breakfast and dinner. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Signed informed consent
- Age 18-55 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 starting 1 month prior to study start
Key exclusion criteria (10 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 |
|---|---|---|
| Milk protein | Dietary supplement | Milk protein |
| Milk protein rich in phospholipids | Dietary supplement | Milk protein rich in phospholipids |
Primary outcome
Change of fecal ETEC numbers over time as a marker of intestinal colonization resistance
Time frame: Days -1 and -2 before ETEC challenge and days 1,2,3,4,7 and 15 after challenge
The change over time in fecal ETEC numbers is compared between treatment and placebo group.
Change of total daily fecal output over time as a marker of infectious diarrhea
Time frame: Days -1 and -2 before ETEC challenge and on days 1,2,3,4,7 and 15 after challenge.
The change in the daily fecal output over time is compared between treatment and placebo group.
5 secondary outcomes
Daily Bristol Stool Score as a marker for stool consistency
Time frame: Days -1 and -2 before ETEC challenge and on days 1-15 after challenge.
Gastro-Intestinal Symptom Rating Scale (GSRS) for gastro-intestinal complaints
Time frame: Days -1 and -2 before ETEC challenge and on days 1-15 after challenge
% fecal wet weight as a marker for Diarrhea severity
Time frame: Days -1 and -2 before ETEC challenge and days 1-15 after challenge.
Stool frequency (number of stools per day)
Time frame: Day -1 and -2 and days 0-15
Specific serum antibody response to CFAII
Time frame: Before ETEC challenge and on day 15 after challenge.
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.
- Background: PubMed 12891550Bovee-Oudenhoven IM, Lettink-Wissink ML, Van Doesburg W, Witteman BJ, Van Der Meer R. Diarrhea caused by enterotoxigenic Escherichia coli infection of humans is inhibited by dietary calcium. Gastroenterology. 2003 Aug;125(2):469-76. doi: 10.1016/s0016-5085(03)00884-9.
- Derived from this study: PubMed 26701793Ten Bruggencate SJ, Frederiksen PD, Pedersen SM, Floris-Vollenbroek EG, Lucas-van de Bos E, van Hoffen E, Wejse PL. Dietary Milk-Fat-Globule Membrane Affects Resistance to Diarrheagenic Escherichia coli in Healthy Adults in a Randomized, Placebo-Controlled, Double-Blind Study. J Nutr. 2016 Feb;146(2):249-55. doi: 10.3945/jn.115.214098. Epub 2015 Dec 23.
- Related InfoLink provided by the sponsor.
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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.
Sandra Ten Bruggencate, PhD principal investigator
NIZO food research, The Netherlands
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Milk protein and Milk protein rich in phospholipids in people with Bacterial Infection and Diarrhea, 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 6 inclusion and 10 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?
Change of fecal ETEC numbers over time as a marker of intestinal colonization resistance (time frame: Days -1 and -2 before ETEC challenge and days 1,2,3,4,7 and 15 after challenge). 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 NCT01800396, which also lists 2 linked publications.
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.