Clinical trial NCT01049386: Intestinal Permeability
Official title: Methods to Examine Intestinal Permeability Under Different Conditions
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Intestinal Permeability
Keywords: intestinal permeability
health
sugar absorption
intestinal permeability examined in different men (lean vs obese) and different conditions (no breakfast and high-fat breakfast)
Lead sponsor: TNO
Sponsor class: OTHER
Collaborators: name: Netherlands: Ministry of Health, Welfare and Sports
First posted: 2010-01-14
Enrollment: 16
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: Rationale: Intestinal permeability of subjects can vary depending on their health status. It is therefore important to be able to measure and quantify intestinal permeability in a standardized way. Subjects with intestinal complaints (like irritable bowel disorder) or obese subjects have been found to have increased intestinal permeability. Different physiological conditions might affect intestinal permeability (IP) further.

In the clinic, sugar absorption tests and different blood and urine markers have been used to quantify IP. The sugars sucrose, mannitol, sucralose and lactulose are absorbed differently in the small or large intestines, resulting in different sugar levels in urine. This indicates the level of intestinal permeability and the location of increased permeability which is more or less permeable.

A high-fat meal could be used as a challenge test to increase IP in subjects even further. After a high fat meal, lipopolysaccharide (LPS) could be co-transported with chylomicrons. Small amounts of LPS co-transit with dietary fat from the gut after a high-fat meal, which thereby increases plasma LPS concentrations.

Because of the above mentioned reasons, it could be relevant to determine intestinal permeability and plasma LPS concentration after consumption of a high-fat diet.

Different methods will be used to determine the intestinal permeability in lean and obese men, under different conditions. New parameters, like intestinal (I) fatty acid binding protein (I-FABP), liver (L)-FABP, LPS and inflammatory markers will be measured and related to outcomes of tests, to examine the relation with intestinal permeability.

The association of IP with whole body electrical resistance will be examined, to determine usefulness of a candidate non-invasive method for IP investigation.

Detailed description: Study design: The study is designed as a randomized, cross-over and open study.

Study population: 16 healthy, lean (BMI 20-25 kg.m-2) and obese (BMI 30-35 kg.m-2) male subjects will participate in the study, aged between 18-45 years.

Intervention: On two different test days eight lean and eight obese men will be supplied with a sugar drink to examine intestinal permeability under normal conditions and in combination with an oral fat load to examine intestinal permeability under stressed conditions.

Main study parameters/endpoints: Intestinal permeability will be examined with an absorption test using four different sugars (sucrose, mannitol, sucralose and lactulose). New markers of intestinal permeability, like I-FABP, L-FABP, LPS and inflammatory markers will be measured as well.

Eligibility criteria: Inclusion Criteria:

1. Healthy as assessed by the

   * health and lifestyle questionnaire (P8738 F02; in Dutch)
   * results of the pre-study laboratory tests
2. Males aged ≥ 18 and ≤ 45 years at Day 01 of the study
3. Body Mass Index (BMI): for the lean : ≥ 20 and ≤ 25 kg/m2; obese ≥ 30 and ≤ 35 kg/m2
4. Normal Dutch eating habits as assessed by P8738 F02
5. Voluntary participation
6. Having given written informed consent
7. Willing to comply with the study procedures
8. Appropriate veins for blood sampling/cannula insertion according to TNO
9. Willing to accept use of all nameless data, including publication, and the confidential use and storage of all data for at least 15 years
10. 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 30-90 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, inhalator administration of substances
3. Having a history of medical or surgical events that may significantly affect the study outcome, including cardiovascular disease or hypertension, stomach and intestinal complaints (and medication), pre-diabetes and Diabetes Mellitus
4. Having stomach and/or intestinal complaints after consumption of a high-fat meal
5. Usage of NSAIDs and/or acetylsalicylic acid (for example ibuprofen, diclofenac, naproxen or aspirin)
6. Smoking
7. Alcohol consumption ( \> 28 units/week)
8. Reported unexplained weight loss or gain of \> 2 kg in the month prior to the pre-study screening
9. Reported slimming or medically prescribed diet
10. Recent blood donation (\<1 month prior to the start of the study)
11. Not willing to give up blood donation during the study.
12. Personnel of TNO Quality of Life, their partner and their first and second degree relatives
13. Not having a general practitioner
14. Not willing to accept information transfer, concerning participation in the study, or information regarding his health, like laboratory results, findings at anamnesis or physical examination and eventual adverse events to and from his general practitioner.

Primary outcomes:
measure: intestinal absorption (measured with the four sugar absorption test)
timeFrame: 24 hours
Secondary outcomes:
measure: Different biomarkers for intestinal absorption.
timeFrame: 6 hours
Other outcomes:
Locations:
city: Zeist
country: Netherlands
facility: TNO Quality of Life
state: Utrecht
Study officials:
affiliation: TNO
name: W J Pasman, PhD
role: PRINCIPAL_INVESTIGATOR
References: