Intestinal Barrier Function and Probiotics.

This study has been completed.
Sponsor:
Collaborators:
VSL Pharmaceuticals
NIZO Food Research
Information provided by:
TNO
ClinicalTrials.gov Identifier:
NCT01241201
First received: October 29, 2010
Last updated: July 20, 2011
Last verified: July 2011
  Purpose

Rationale: Enterotoxigenic Escherichia coli (ETEC) bacteria adhere to the mucosa of the proximal intestines. There it produces an toxin which presents a local and relevant challenge to the intestines. This is proposed to give an indication of general resistance and/or the local resistance of the intestines. The sequel of events of mucosal inflammation will be characterized in this study. In addition we will evaluate the effects of probiotics by comparing the infection symptoms and by measuring faecal weight and mucus in faeces.

Objective: The main objective of this study is to investigate the effect of probiotics on the sequels of ETEC administration as intestinal permeability, inflammation and clinical signs as total faecal output, relative faecal dry weight and mucin excretion in faeces. In addition, the sequels of the mucosal inflammation will be characterized and biomarkers will be searched.


Condition Intervention
Intestinal Permeability
Challenge Test
Intestinal Health
Inflammation
Dietary Supplement: Priobiotic supplement VSL#3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: A Study Proposal to Investigate the Sequels of Mucosal Inflammation Caused by ETEC Infection - the Effects of Probiotics.

Resource links provided by NLM:


Further study details as provided by TNO:

Primary Outcome Measures:
  • Faecal weight and mucus (diarrhoea) [ Time Frame: day 01 ] [ Designated as safety issue: No ]
    Characteristics of the faeces will be determined (% wet and dry weight)

  • Faecal weight and mucus (diarrhoea) [ Time Frame: day 20 ] [ Designated as safety issue: No ]
    Characteristics of the faeces will be determined (% wet and dry weight)

  • Faecal weight and mucus (diarrhoea) [ Time Frame: day 22 ] [ Designated as safety issue: No ]
    Characteristics of the faeces will be determined (% wet and dry weight)

  • Faecal weight and mucus (diarrhoea) [ Time Frame: day 23 ] [ Designated as safety issue: No ]
    Characteristics of the faeces will be determined (% wet and dry weight)

  • Faecal weight and mucus (diarrhoea) [ Time Frame: day 24 ] [ Designated as safety issue: No ]
    Characteristics of the faeces will be determined (% wet and dry weight)


Secondary Outcome Measures:
  • intestinal permeability [ Time Frame: day 01, 20 and day 22 ] [ Designated as safety issue: No ]
    Determine the intestinal permeability before and after probiotic supplementation and especially after infection of the intestines.


Enrollment: 32
Study Start Date: October 2010
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
placebo for probiotic treatment
Dietary Supplement: Priobiotic supplement VSL#3
four weeks, twice daily two sachets of VSL#3, a priobitics mixture

Detailed Description:

Study population: 36 Healthy male volunteers; age >= 21 and <= 40 years. Intervention: One group receives twice daily two sachets containing 450 billion live freeze-dried lactic acid bacteria per sachet and the other group receives twice daily two placebo sachets.

Study design: The study is designed as a randomized, parallel, placebo-controlled, double-blind study. Study substance (probiotics) and placebo will be given during 4 weeks.

Main study parameters/endpoints: The main study parameter is the percent change in faecal dry weight and total faecal output between the probiotics group and the placebo group. In addition, intestinal permeability, inflammation and other clinical symptoms will be evaluated.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: In this study healthy male volunteers will be challenged with an attenuated ETEC strain after three weeks of either probiotics or placebo. This infection will lead to a mild traveller's diarrhoea in the subjects during approximately three days maximally. Sequels of this infection and the effects of commercially available probiotics compared to placebo will be followed up. The subjects will therefore collect their faeces on several days, record their defecation pattern and gastro-intestinal complaints during four weeks, undergo a physical examination and five venapunctions, and visit our facilities in total on 8 days (excluding two pre-study visits). The oral administration of probiotics in a healthy population is not associated with risk.

  Eligibility

Ages Eligible for Study:   21 Years to 40 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Healthy as assessed by the

    • health and lifestyle questionnaire, (P9067 F02; in Dutch)
    • physical examination
    • results of the pre-study laboratory tests
  2. Males, Age >= 21 and <= 40 years at Day 01 of the study
  3. Body Mass Index (BMI) >= 20 and < 33 kg/m2. Preferably in high and low body fat mass ranges as to be determined by waist circumference
  4. Normal Dutch eating habits as assessed by P9067 F02
  5. Voluntary participation
  6. Having given written informed consent
  7. Willing to comply with the study procedures, including the ETEC challenge
  8. Willing to accept use of all nameless data, including publication, and the confidential use and storage of all data for at least 15 years
  9. Willing to accept the disclosure of the financial benefit of participation in the study to the authorities concerned.

Exclusion Criteria:

Subjects with one or more of the following characteristics will be excluded from participation:

  1. Participation in any clinical trial including blood sampling and/or administration of substances up to 90 days before Day 01 of this study
  2. Participation in any non-invasive clinical trial up to 30 days before Day 01 of this study, including no blood sampling and/or oral, intravenous, inhalatory administration of substances
  3. Having a history of medical or surgical events that may significantly affect the study outcome, including gastrointestinal illness or surgical operations,
  4. Use of antibiotics, immunosuppressive drugs, antacids, laxatives or anti-diarrhoeal drugs in the last 3 months before the study
  5. Alcohol consumption > 28 units/week for males
  6. Reported unexplained weight loss or gain of > 2 kg in the month prior to the pre-study screening
  7. Reported slimming or medically prescribed diet
  8. Reported vegan, vegetarian or macrobiotic
  9. Not willing to be off working as a food handler, in child care or as a healthcare worker with direct patient contact during the week of ETEC contamination
  10. Not willing to give up blood donation during the study.
  11. Personnel of TNO Quality of Life, their partner and their first and second degree relatives
  12. Not having a general practitioner
  13. Not willing to accept information-transfer concerning participation in the study, or information regarding his/her health, like laboratory results, findings at anamnesis or physical examination and eventual adverse events to and from his general practitioner.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01241201

Locations
Netherlands
TNO Quality of Life
Zeist, Utrecht, Netherlands, 3704HE
Sponsors and Collaborators
TNO
VSL Pharmaceuticals
NIZO Food Research
Investigators
Principal Investigator: W J Pasman, PhD TNO
  More Information

Publications:
Responsible Party: Ministry of Health, Welfare and Sport
ClinicalTrials.gov Identifier: NCT01241201     History of Changes
Other Study ID Numbers: P9067
Study First Received: October 29, 2010
Last Updated: July 20, 2011
Health Authority: Netherlands: Dutch Health Care Inspectorate

Keywords provided by TNO:
intestinal health
probiotics
inflammation
biomarkers

Additional relevant MeSH terms:
Inflammation
Pathologic Processes

ClinicalTrials.gov processed this record on September 30, 2014