Effect of Acute and Sub-acute Administration of Gluten on Extra-intestinal and Gastrointestinal Symptoms in Healthy Subjects

Study Overview
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Brief Summary
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The investigators will investigate the effects of acute and sub-acute administration of gluten on mood, intestinal permeability, gastrointestinal symptoms and gut peptide levels in healthy volunteers (HV).

Official Title
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Effect of Acute and Sub-acute Administration of Gluten on Extra-intestinal and Gastrointestinal Symptoms in Healthy Subjects

Conditions
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Healthy Volunteers, Gluten

Intervention / Treatment
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* Other: Gluten
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body Mass Index (BMI) of 20 - 25 kg/m2 Stable body weight for at least 3 months prior to the start of the study Exclusion Criteria: Medical Coeliac disease (excluded either by absence of the HLA-DQ2 and HLA-DQ8 haplotype or by a normal duodenal biopsy (Marsh 0) performed at endoscopy while on a gluten containing diet in individuals expressing the HLA-DQ2 (human leukocyte antigen) or HLA-DQ8 haplotype) Abdominal or thoracic surgery. Exception: appendectomy Gastrointestinal, endocrine or neurological diseases Cardiovascular, respiratory, renal or urinary diseases Hypertension Diagnosed food or drug allergies Psychiatric disorders Eating disorders Depressive disorders Anxiety disorders Psychotic disorders Restraint or emotional eating Dieters, especially no gluten-free diet or a diet low on gluten Medication on a regular basis, exception: oral contraception Smoking History of cannabis use or any other drug of abuse for at least 12 months prior to the study Alcohol abuse (more than 21 units of alcohol for men, more than 14 units for woman per week) Pregnant or breastfeeding women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: single-blinded, randomised controlled, cross-over study
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Gluten<br>Patients receive 16 g of gluten acutely and afterwards 2 glutenfree muffins with 8 g of gluten for 5 days sub-acutely | Other: Gluten<br>* Tereos<br>|
| Placebo Comparator: Placebo<br>Patients receive 16 g of whey protein acutely and afterwards 2 glutenfree muffins for 5 days sub-acutely | Other: Placebo<br>* Whey protein from Nestlé Healthy Science<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effect of gluten acutely and sub-acutely on extraintestinal symptoms in HV measured on the Positive and Negative Affect Schedule | Change from baseline. Scores can be 'very slightly or not at all', 'a little', 'moderately', 'quite a bit', 'extremely'. Measured at day 0, day 15, day 20, day 36 and day 41. | At the beginning of test visit 0 (day 0), visit 1 (at day 15), test visit 2 (at day 20), after test visit 3 (at day 36), after test visit 4 (at day 41) | 
| The effect of gluten acutely and sub-acutely on extraintestinal symptoms in HV measured on the Profile of Mood State. | Change from baseline. Scores are measured on the Visual Analogue Scale. The scale is ranged 0 - 10, in which 0 no occurrence of the symptom and 10 a lot occurrence of the symptom. Measured at day 0, day 15, day 20, day 36 and day 41. | At the beginning of test visit 0 (day 0), visit 1 (at day 15), test visit 2 (at day 21), after test visit 3 (at day 36), after test visit 4 (at day 41) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effect of gluten acutely and sub-acutely on gastrointestinal symptoms in HV measured on the visual analogue scale for gastrointestinal symptoms | Scores are measured on the Visual Analogue Scale. With '0' no complaints and '10' a lot of complaints (change from baseline). | At the beginning of test visit 0 (day 0), visit 1 (at day 15), test visit 2 (at day 21), after test visit 3 (at day 36), after test visit 4 (at day 41) | 
| The effect of gluten acutely and sub-acutely on intestinal permeability (using the lactulose mannitol ratio) | Investigate change in intestinal permeability after gluten administration. In the urine we can measure the ratio lactulose/mannitol. This can be measured using High Performance Liquid Chromatography | At the beginning of test visit 0 (day 0), visit 1 (at day 15), test visit 2 (at day 20), after test visit 3 (at day 36), after test visit 4 (at day 41) | 
| Effect of acute and sub-acute gluten administration on high sensitive reactive protein levels in blood samples | Change in high sensitive reactive protein levels measured at day 0, day 21 and day 41. | During test visit 0 (day 0), test visit 2 (at day 21), after test visit 4 (at day 41) | 
| Effect of acute and sub-acute gluten administration on Lipopolysaccharide-Binding Protein levels in blood samples | Change in lipopolysaccharide-binding protein levels measured at day 0, day 21 and day 41. | During test visit 0 (day 0), test visit 2 (at day 21), after test visit 4 (at day 41) | 
| Effect of acute and sub-acute gluten administration on Lipopolysaccharide levels in blood samples | Change in lipopolysaccharide levels measured at day 0, day 21 and day 41. | During test visit 0 (day 0), test visit 2 (at day 21), after test visit 4 (at day 41) | 
| Effect of acute and sub-acute gluten administration on gut microbiota composition (stool samples) | Change in gut microbiota composition (compared to day 0) with focus on: Bifidobacterium, Lactobacillus, Enterobacteriaceae, E. coli; measured in stool samples. Analyses will provide an overall view of the gut microbiota composition. | After test visit 0 (day 0), day 13 and day 14, after test visit 1 (day 15), day 16, 17, 18, 19 and 20, two days before test visit 3 (day 34 and 35), day 36, 37, 38, 39, 40 | 
| Effect of acute and sub-acute gluten administration on cortisol awakening response (saliva samples) | Change in cortisol levels between gluten and placebo administration (saliva samples). Measured using an ELISA assay. | Day before test visit 1 (day 14), test visit 1 (day 15), test visit 2 (day 21), day before test visit 3 (day 35), test visit 3 (day 36) and test visit 4 (day 41) |