Gluten and (Extra-)Intestinal Symptoms in NCGS

NCT ID: NCT05779358

Last Updated: 2023-03-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 84 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-19
• Study Completion Date: 2022-02-15

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:

1. Participants with the expectation of receiving gluten-containing bread and actually receiving gluten-containing oat bread during the test day. (E+ G+)

2. Participants with the expectation of receiving gluten-containing bread, but actually receiving gluten-free oat bread during the test day. (E+ G-)

3. Participants with the expectation of receiving gluten-free bread but actually receiving gluten-containing oat bread during the test day. (E- G+)

4. Participants with the expectation of receiving gluten-free bread and actually receiving gluten-free oat bread during the test day. (E- G-)

Detailed Description

One on-site test, starting with baseline measurement (T = 0). Thereafter, subjects are told that they will receive two slices of gluten-containing bread (E+) or gluten-free bread (E-). Consequently, they receive breakfast with two slices of bread (gluten-containing (G+) or gluten-free (G-)).

After breakfast, questionnaires will be completed every hour for 8 hours. After T = 4 hours, participants receive lunch with two slices of the same bread, combined with the same expectancy, that they received at breakfast.

Follow-up measurements include the same questionnaires at the end of day 1 (from end of test day until they go to sleep), at the end of day 2 and at the end of day 3.

Conditions

Non-celiac Gluten Sensitivity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

E+ G+

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

Group Type: ACTIVE_COMPARATOR

Expectancy and gluten

Intervention Type: OTHER

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

E+ G-

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

Group Type: ACTIVE_COMPARATOR

Expectancy and gluten

Intervention Type: OTHER

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

E- G+

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

Group Type: ACTIVE_COMPARATOR

Expectancy and gluten

Intervention Type: OTHER

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

E- G-

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

Group Type: PLACEBO_COMPARATOR

Expectancy and gluten

Intervention Type: OTHER

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

Interventions

Expectancy and gluten

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

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Leeds

OTHER

Sponsor Role: collaborator

Wageningen University

OTHER

Sponsor Role: collaborator

Maastricht University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Daisy MAE Jonkers, Prof, PhD

Role: PRINCIPAL_INVESTIGATOR

Maastricht University

Louise Dye, Prof, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Leeds

Locations

Maastricht University

Maastricht, , Netherlands

Wageningen University

Wageningen, , Netherlands

University of Leeds

Leeds, , United Kingdom

Countries

Netherlands; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 38040019 (View on PubMed)

Other Identifiers

METC183011

Identifier Type: OTHER

Identifier Source: secondary_id

NL64850.068.18

Identifier Type: -

Identifier Source: org_study_id