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

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).

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers, Gluten
• Intervention / Treatment: Other: Gluten; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Jan Tack
  • Leuven, Belgium, 3000
    • TARGID

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2017
• Primary Completion (Actual): April 2, 2018
• Study Completion (Actual): April 2, 2018

Study Registration Dates

• First Submitted: October 11, 2018
• First Submitted That Met QC Criteria: January 7, 2019
• First Posted (Actual): January 9, 2019

Study Record Updates

• Last Update Posted (Actual): January 9, 2019
• Last Update Submitted That Met QC Criteria: January 7, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: S58915

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No