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

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.

Study Overview

• Status: Unknown
• Conditions: NCGS; Gluten
• Intervention / Treatment: Other: Gluten; Other: Placebo

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

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Recruiting
    • Jan Tack
    • Contact: Jan Tack; Phone Number: 498797124; Email: jan.tack@med.kuleuven.be
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium
      • Recruiting
      • TARGID
      • Contact: Annelies Geeraerts; Phone Number: 016377034; Email: Annelies.Geeraerts@kuleuven.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Gluten; 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; Tereos
Placebo Comparator: Placebo; Patients will receive acutely 16 g of whey protein and 2 glutenfree muffins, twice a day, during 5 days	Other: Placebo; Nestlé Health 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 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)

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven

Study record dates

Study Major Dates

• Study Start (Actual): May 11, 2017
• Primary Completion (Anticipated): January 1, 2022
• Study Completion (Anticipated): January 1, 2022

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

• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity
• Other Study ID Numbers: S60127

Drug and device information, study documents

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