Milk Ingredients and Resistance Against E-coli-induced GastroEnteritis (MIRAGE) (MIRAGE)

August 26, 2015 updated by: NIZO Food Research

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).

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 Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Ede, Netherlands, 6718ZB
        • NIZO food research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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.

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)
  • ETEC detected in fecal sample (collected at screening)
  • Vegetarians
  • Vegans
  • Heavy alcohol use (>4 consumptions/day or >20/week)
  • Drug use

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Milk protein
Milk powder, twice daily at breakfast and dinner.
Dietary supplement: Milk protein
Experimental: Milk protein rich in phospholipids
Milk powder, twice daily at breakfast and dinner.
Dietary supplement: Milk protein rich in phospholipids

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
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
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.
Days -1 and -2 before ETEC challenge and on days 1,2,3,4,7 and 15 after challenge.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
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
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.
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
Days -1 and -2 before ETEC challenge and on days 1-15 after challenge
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.
Before ETEC challenge and on day 15 after challenge.

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Time Frame
Calprotectin in feces
Time Frame: Before ETEC challenge and on day 2 and 3 after challenge.
Before ETEC challenge and on day 2 and 3 after challenge.
Total fecal and salivary sIgA
Time Frame: Before ETEC challenge and on day 3 and 4 after challenge.
Before ETEC challenge and on day 3 and 4 after challenge.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
NIZO Food Research

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Arla Foods
Denmark

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Sandra Ten Bruggencate, PhD, NIZO food research, The Netherlands

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2013

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2013

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 21, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 25, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 27, 2013

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 27, 2015

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 26, 2015

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NL41768.081.12

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Gastroenteritis

Clinical Trials on Milk protein

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings