Gluten and (Extra-)Intestinal Symptoms in NCGS

NCT05779358 | Completed

• 2 other identifiers: NL64850.068.18METC183011
• Study Type: interventional
• Target: 84
• Locations: 2 countries
• Sites: 3

Brief Summary

The goal of this randomized, double-blind, placebo-controlled study is to investigate the effect of expectancy related to gluten consumption versus actual gluten intake on overall GI symptoms in individuals with non-coeliac gluten sensitivity (NCGS) The main questions it aims to answer are:

• what is the effect of consumer expectancy, related to either gluten-containing or gluten-free oat bread, on short-term (within 8 hours) overall GI symptoms in individuals with NCGS?
• what is the effect of actual gluten intake on short-term (within 8 hours) overall GI symptoms in individuals with NCGS Participants will be randomised into four groups:
• Participants with the expectation of receiving gluten-containing bread and actually receiving gluten-containing oat bread during the test day. (E+ G+)
• Participants with the expectation of receiving gluten-containing bread, but actually receiving gluten-free oat bread during the test day. (E+ G-)
• Participants with the expectation of receiving gluten-free bread but actually receiving gluten-containing oat bread during the test day. (E- G+)
• Participants with the expectation of receiving gluten-free bread and actually receiving gluten-free oat bread during the test day. (E- G-)

Conditions

Non-celiac Gluten Sensitivity

Keywords

Non-Coeliac Gluten Sensitivity; NCGS; Gluten; Gastrointestinal symptoms

Outcome Measures

Primary Outcomes (1)

• Overall gastrointestinal symptom score (short term)

  Change from baseline, measured on a Visual Analogue Scale ranged from 0-100, in which 0 is absence of symptoms and 100 is severe symptoms.

  Test day: baseline (T = 0 hours), hourly after breakfast (T = 1 hour until T = 4 hours), and hourly after lunch (T = 5 hours until T = 8 hours)

Secondary Outcomes (8)

• Individual gastrointestinal symptom scores (short term)

  Test day: baseline (T = 0 hours), hourly after breakfast (T = 1 hour until T = 4 hours), and hourly after lunch (T = 5 hours until T = 8 hours)

• Individual extra-intestinal symptom scores (short term)

  Test day: baseline (T = 0 hours), hourly after breakfast (T = 1 hour until T = 4 hours), and hourly after lunch (T = 5 hours until T = 8 hours)

• Average stool frequency and consistency (short term)

  Test day: baseline (T = 0 hours), hourly after breakfast (T = 1 hour until T = 4 hours), and hourly after lunch (T = 5 hours until T = 8 hours)

• Mood (short term)

  Test day: baseline, every hour after breakfast (T = 1 hour until T = 8 hours)

• Overall and individual gastrointestinal symptom score (long-term)

  Follow-up: end of day 1 (time from end of test day (t = 8 hours) until end of that day), end of day 2, end of day 3

Other Outcomes (2)

• Participant characteristics in relation to NCGS

  Data on medical history, demographic factors and adherence to gluten-free diet during the screening visit as part of the screening process. Data on psychological factors will be collected after inclusion of subjects, before the start of the test day.

• Food intake and medication use

  Follow-up: end of day 1 (time from end of test day (t = 8 hours) until end of that day), end of day 2, end of day 3

Study Arms (4)

E+ G+

ACTIVE COMPARATOR

Participants with the expectation of receiving gluten-containing bread and actually receiving gluten-containing oat bread during the test day.

Other: Expectancy and gluten

E+ G-

ACTIVE COMPARATOR

Participants with the expectation of receiving gluten-containing bread, but actually receiving gluten-free oat bread during the test day.

Other: Expectancy and gluten

E- G+

ACTIVE COMPARATOR

Participants with the expectation of receiving gluten-free bread but actually receiving gluten-containing oat bread during the test day.

Other: Expectancy and gluten

E- G-

PLACEBO COMPARATOR

Participants with the expectation of receiving gluten-free bread and actually receiving gluten-free oat bread during the test day.

Other: Expectancy and gluten

Interventions

Expectancy and gluten OTHER

Effect of expectancy to receive gluten and/or actual gluten intake

E+ G+; E+ G-; E- G+; E- G-

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Develops self-reported GI symptoms within 8 hours after a single intake of gluten-containing products, without a diagnosis of an organic GI disease;
• Following of willing to follow a gluten-free or gluten-restricting diet (based on a gluten-free dietary compliance questionnaire of Biagi et al. (only group 2, 3 and 4 will be eligible), for at least 1 week prior to study participation and willing to continue with this throughout the study;
• Asymptomatic or only mildly symptomatic (overall (GI) symptom score with VAS \< 30mm) while on the gluten-free diet;
• Willing to participate in a study in which they have to consume 4 slices of gluten-containing or gluten-free bread for breakfast and lunch during the test day;
• Willing and able to give written informed consent and to understand, participate and comply with the research project requirements.

You may not qualify if:

• Coeliac disease;
• Wheat allergy;
• Presence of an organic GI disease (such as inflammatory bowel disease) or other disease which may interfere with NCGS symptoms (upon judgment of the physician clinical investigator);
• Previous major abdominal surgery or radiotherapy interfering with GI function:
• Uncomplicated appendectomy, cholecystectomy and hysterectomy allowed unless within the past 6 months;
• Other surgery may be allowed based upon judgment of the physician-clinical investigator;
• Use of medication potentially influencing GI function and/or NCGS symptoms is allowed, provided that dosing has been stable for \> 6 weeks before enrolment;
• Administration of antibiotics, probiotic or prebiotic supplements, investigational drugs or participation in any scientific intervention study, which may interfere with this study (to be decided by the principle investigator), in the 14 days prior to the study
• Excessive use of alcohol (\>15 alcoholic units per week), or other drugs;
• Plan to lose weight or follow a specific diet within the study period;
• Any malignancy;
• Pregnancy or breastfeeding;
• Insufficient fluency of the Dutch (for Maastricht and Wageningen) or Englisch (for Leeds) language.

Sponsors & Collaborators

• Maastricht University: lead
• University of Leeds: collaborator
• Wageningen University: collaborator

Study Sites (3)

Maastricht University

Maastricht, Netherlands

Location

Wageningen University

Wageningen, Netherlands

Location

University of Leeds

Leeds, United Kingdom

Location

Related Publications (1)

• de Graaf MCG, Lawton CL, Croden F, Smolinska A, Winkens B, Hesselink MAM, van Rooy G, Weegels PL, Shewry PR, Houghton LA, Witteman BJM, Keszthelyi D, Brouns FJPH, Dye L, Jonkers DMAE. The effect of expectancy versus actual gluten intake on gastrointestinal and extra-intestinal symptoms in non-coeliac gluten sensitivity: a randomised, double-blind, placebo-controlled, international, multicentre study. Lancet Gastroenterol Hepatol. 2024 Feb;9(2):110-123. doi: 10.1016/S2468-1253(23)00317-5. Epub 2023 Nov 28.

  PMID: 38040019 DERIVED

MeSH Terms

Interventions

Glutens

Intervention Hierarchy (Ancestors)

Prolamins; Grain Proteins; Plant Proteins; Proteins; Amino Acids, Peptides, and Proteins; Seed Storage Proteins

Study Officials

• Daisy MAE Jonkers, Prof, PhD

  Maastricht University

  PRINCIPAL INVESTIGATOR

• Louise Dye, Prof, PhD

  University of Leeds

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Investigator and outcomes assessor know expectancy (E+ or E-) but is blinded to the actual gluten intervention (G+ or G-). Participants are told the expectancy, but are unaware of the actual nature of the intervention: they are unaware that there is a 50% chance of receiving either G+ or G- bread, regardless of what they were told.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2023
• First Posted: March 22, 2023
• Study Start: October 19, 2018
• Primary Completion: January 31, 2022
• Study Completion: February 15, 2022
• Last Updated: March 22, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1); NL (2)