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

Diarrhea Clinical Trial

— MIRAGE  

Official title:

A Randomized, Placebo-controlled, Double Blind Volunteer Study Into the Effect of Milk Ingredients on Gastroenteritis Caused by an Attenuated E.Coli.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01800396
• Other study ID #: NL41768.081.12
• Status: Completed
• Phase: N/A
• First received: February 21, 2013
• Last updated: August 26, 2015
• Start date: February 2013
• Est. completion date: May 2013

Study information

• Verified date: August 2015
• Source: NIZO Food Research
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: May 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Bacterial Infection
• Bacterial Infections
• Diarrhea
• Gastroenteritis

Intervention

Dietary Supplement:
• Milk protein

• Milk protein rich in phospholipids

Locations

Country	Name	City	State
Netherlands	NIZO food research	Ede

Sponsors (3)

Lead Sponsor	Collaborator
NIZO Food Research	Arla Foods, Denmark

Country where clinical trial is conducted

Netherlands, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Calprotectin in feces		Before ETEC challenge and on day 2 and 3 after challenge.	No
Other	Total fecal and salivary sIgA		Before ETEC challenge and on day 3 and 4 after challenge.	No
Primary	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.	Days -1 and -2 before ETEC challenge and days 1,2,3,4,7 and 15 after challenge	No
Primary	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.	Days -1 and -2 before ETEC challenge and on days 1,2,3,4,7 and 15 after challenge.	No
Secondary	Daily Bristol Stool Score as a marker for stool consistency		Days -1 and -2 before ETEC challenge and on days 1-15 after challenge.	No
Secondary	Gastro-Intestinal Symptom Rating Scale (GSRS) for gastro-intestinal complaints		Days -1 and -2 before ETEC challenge and on days 1-15 after challenge	No
Secondary	% fecal wet weight as a marker for Diarrhea severity		Days -1 and -2 before ETEC challenge and days 1-15 after challenge.	No
Secondary	Stool frequency (number of stools per day)	Days -1 and -2 before ETEC challenge and on days 1-15 after challenge	Day -1 and -2 and days 0-15	No
Secondary	Specific serum antibody response to CFAII		Before ETEC challenge and on day 15 after challenge.	No

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