Clinical trial NCT05779358: Gluten and (Extra-)Intestinal Symptoms in NCGS
Official title: The Effects of Bread Consumption on Intestinal and Extra-intestinal Symptoms in Non-coeliac Gluten Sensitivity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Non-celiac Gluten Sensitivity
Keywords: Non-Coeliac Gluten Sensitivity
NCGS
Gluten
Gastrointestinal symptoms
Lead sponsor: Maastricht University
Sponsor class: OTHER
Collaborators: name: University of Leeds
name: Wageningen University
First posted: 2023-03-22
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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.

Primary outcomes:
measure: Overall gastrointestinal symptom score (short term)
timeFrame: 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:
measure: Individual gastrointestinal symptom scores (short term)
timeFrame: 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)
measure: Individual extra-intestinal symptom scores (short term)
timeFrame: 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)
measure: Average stool frequency and consistency (short term)
timeFrame: 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)
measure: Mood (short term)
timeFrame: Test day: baseline, every hour after breakfast (T = 1 hour until T = 8 hours)
measure: Overall and individual gastrointestinal symptom score (long-term)
timeFrame: 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
measure: Individual extra-intestinal symptom scores (long term)
timeFrame: 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
measure: Average stool frequency and consistency (long term)
timeFrame: 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
measure: Mood (long term)
timeFrame: 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:
measure: Participant characteristics in relation to NCGS
timeFrame: 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.
measure: Food intake and medication use
timeFrame: 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
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht University
city: Wageningen
country: Netherlands
facility: Wageningen University
city: Leeds
country: United Kingdom
facility: University of Leeds
Study officials:
affiliation: Maastricht University
name: Daisy MAE Jonkers, Prof, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Leeds
name: Louise Dye, Prof, PhD
role: PRINCIPAL_INVESTIGATOR
References: