Intestinal Permeability
Condition: Intestinal Permeability
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): No intervention; Sugar absorption test
Intervention type(s): Other; Procedure
Intervention description(s): In obese and lean subjects the intestinal absorption will be examined under normal conditions with sugar drink, and when disturbed by a high-fat breakfast.; On one of the test days the subjects will consume a high-fat breakfast.
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: intestinal permeability; health; sugar absorption; intestinal permeability examined in different men (lean vs obese) and different conditions (no breakfast and high-fat breakfast)