Effect of Acute and Sub-acute Administration of Gluten on Extra-intestinal and Gastrointestinal Symptoms in Patients With Non-coeliac Gluten Sensitivity

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, gut microbiota and cortisol levels in NCGS patients.

Official Title
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Effect of Acute and Sub-acute Administration of Gluten on Extra-intestinal and Gastrointestinal Symptoms in Patients With Non-coeliac Gluten Sensitivity

Conditions
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NCGS, 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: Non-coeliac gluten sensitivity patients Previous symptoms of IBS fulfilling Rome III criteria that self reportedly improved with a gluten-free diet Symptoms currently well controlled on a gluten-free diet Adherence to the gluten-free diet for at least 6 weeks prior to recruitment 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 or HLA-DQ8 haplotype) IgA anti-tissue-transglutaminase or IgG anti-deaminated gliadin peptide positive 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 Abdominal or thoracic surgery. Exception: appendectomy Gastrointestinal, endocrine or neurological diseases Cardiovascular, respiratory, renal or urinary diseases Hypertension Food or drug allergies Psychiatric disorders Eating disorders Depressive disorders Anxiety disorders Psychotic disorders Restraint or emotional eating Medication on a regular basis, exception: oral contraception 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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: single-blinded, randomised - controlled, crossover
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Gluten<br>Patients will receive acutely 16 g of gluten and 2 muffins glutenfree with 8 g of gluten, twice a day, during 5 days | Other: Gluten<br>* Tereos<br>|
| Placebo Comparator: Placebo<br>Patients will receive acutely 16 g of whey protein and 2 glutenfree muffins, twice a day, during 5 days | Other: Placebo<br>* Nestlé Health 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 NCGS patients 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' | 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 35), after test visit 4 (at day 40) | 
| The effect of gluten acutely and sub-acutely on extraintestinal symptoms in NCGS patients measured on the Profile of Mood State | Scores are measured on the Visual Analogue Scale. Change from baseline. 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 21, 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 35), after test visit 4 (at day 40) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effect of gluten acutely and sub-acutely on gastrointestinal symptoms in NCGS patients measured on the visual analogue scale for gastrointestinal symptoms | With '0' no complaints and '10' a lot of complaints (change from baseline). Measured on the Visual Analogue Scale. Measured at day 0, day 15, day 21, 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 35), after test visit 4 (at day 40) | 
| Effect of acute and sub-acute gluten administration on intestinal permeability (lactulose mannitol ratio) | 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 day 0, day 15, day 21, 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) | 
| Effect of acute and sub-acute gluten administration on high sensitive reactive protein levels in bloodsample | 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 bloodsample | 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 bloodsample | 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 | Change in gut microbiota composition (compared to day 0) with focus on: Bifidobacterium, Lactobacillus, Enterobacteriaceae, E. coli (stool samples) | 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 | 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) |