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

NCT01800396 | Completed DMC

• 1 other identifier: NL41768.081.12
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Bacterial Infection; Diarrhea; Gastroenteritis

Keywords

Bacterial infection; Dairy; Diarrhea; Diet; E.Coli; Gastroenteritis; Milk; Stool consistency

Outcome Measures

Primary Outcomes (2)

• 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

• 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.

Secondary Outcomes (5)

• Daily Bristol Stool Score as a marker for stool consistency

  Days -1 and -2 before ETEC challenge and on days 1-15 after challenge.

• Gastro-Intestinal Symptom Rating Scale (GSRS) for gastro-intestinal complaints

  Days -1 and -2 before ETEC challenge and on days 1-15 after challenge

• % fecal wet weight as a marker for Diarrhea severity

  Days -1 and -2 before ETEC challenge and days 1-15 after challenge.

• Stool frequency (number of stools per day)

  Day -1 and -2 and days 0-15

• Specific serum antibody response to CFAII

  Before ETEC challenge and on day 15 after challenge.

Other Outcomes (2)

• Calprotectin in feces

  Before ETEC challenge and on day 2 and 3 after challenge.

• Total fecal and salivary sIgA

  Before ETEC challenge and on day 3 and 4 after challenge.

Study Arms (2)

Milk protein

PLACEBO COMPARATOR

Milk powder, twice daily at breakfast and dinner.

Dietary Supplement: Milk protein

Milk protein rich in phospholipids

EXPERIMENTAL

Milk powder, twice daily at breakfast and dinner.

Dietary Supplement: Milk protein rich in phospholipids

Interventions

Milk protein DIETARY_SUPPLEMENT

Milk protein

Milk protein rich in phospholipids DIETARY_SUPPLEMENT

Milk protein rich in phospholipids

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• NIZO Food Research: lead
• Arla Foods: collaborator
• Denmark: collaborator

Study Sites (1)

NIZO food research

Ede, 6718ZB, Netherlands

Location

Related Publications (2)

• 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.

  PMID: 12891550 BACKGROUND

• Ten 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.

  PMID: 26701793 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Bacterial Infections; Diarrhea; Gastroenteritis; Escherichia coli Infections

Interventions

Milk Proteins; Phospholipids

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Gastrointestinal Diseases; Digestive System Diseases; Enterobacteriaceae Infections; Gram-Negative Bacterial Infections

Intervention Hierarchy (Ancestors)

Animal Proteins, Dietary; Dietary Proteins; Proteins; Amino Acids, Peptides, and Proteins; Food; Diet, Food, and Nutrition; Physiological Phenomena; Milk; Dairy Products; Food and Beverages; Membrane Lipids; Lipids

Study Officials

• Sandra Ten Bruggencate, PhD

  NIZO food research, The Netherlands

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2013
• First Posted: February 27, 2013
• Study Start: February 1, 2013
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: August 27, 2015

Record last verified: 2015-08

Locations

NL (1)