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

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • 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

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
Intervention / Treatment
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

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

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

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

NIZO Food Research

Collaborators

Arla Foods
Denmark

Investigators

  • 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

February 1, 2013

Primary Completion (Actual)

May 1, 2013

Study Completion (Actual)

May 1, 2013

Study Registration Dates

First Submitted

February 21, 2013

First Submitted That Met QC Criteria

February 25, 2013

First Posted (Estimate)

February 27, 2013

Study Record Updates

Last Update Posted (Estimate)

August 27, 2015

Last Update Submitted That Met QC Criteria

August 26, 2015

Last Verified

August 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID 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.

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