Clinical trial NCT04084470: Effects of Different Bread Types in NCWS
Official title: The Effects of the Different Bread Types of Fully Known Composition on Gastrointestinal Symptoms in Individuals With Non-coeliac Wheat Sensitivity.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Non-Coeliac Wheat Sensitivity (NCWS)
Keywords: Non-Coeliac Wheat Sensitivity
Wheat Sensitivity
Bread
Wheat
Gastrointestinal symptoms
Lead sponsor: Maastricht University
Sponsor class: OTHER
Collaborators: name: Wageningen University
First posted: 2019-09-10
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Double-blind randomized cross-over study
Primary purpose: BASIC_SCIENCE

Brief summary: Although wheat and gluten containing food products are generally considered to be healthy, a large number of individuals in the general population reduces or limits their intake and/or replaces wheat by other grains because of possible symptoms. This non-coeliac wheat sensitivity (NCWS) is accompanied by a range of (extra-)intestinal complaints soon after consuming wheat, which improve after wheat withdrawal. Evidence for a biological mechanism and for the exact contributing compound is limited. Furthermore, the impact of grain type, bread processing and the resulting compositional changes in bread on gastrointestinal tolerability in NCWS is unclear, especially as consumed part of a typical daily human diet.

The objective of this study is to investigate the effects of well-characterised breads on (extra-)intestinal symptoms in individuals with NWGS using two double-blind randomized cross-over design (study A and B). Subjects are required to avoid any products that cause GI symptoms (e.g. wheat products) during the trial. The investigators hypothesize that grain type and processing will have a different effect on the primary outcomes.

In addition, we want to explore the in vitro effect of each bread type on gut microbiota composition and activity.


Eligibility criteria: Inclusion Criteria:

* Develops of self-reported GI symptoms within 12 hours after a single intake of bread;
* Age between 18-70 years;
* Asymptomatic or only mildly symptomatic (overall) GI symptoms score with VAS \< 30mm) while on the gluten-free/gluten-restricted diet;
* Must have a freezer (-18ºC) to store the study breads during the study;
* Willing and able to give written informed consent and to understand, participate and comply with the research project requirements.

Exclusion Criteria:

* Medical history of coeliac disease, wheat allergy, inflammatory bowel disease, presence of an organic gastrointestinal (GI) disease (such as inflammatory bowel disease) or other disease which may interfere with NCWS symptoms (upon judgment of the physician-clinical investigator (Dr. Keszthelyi, Gastroenterologist MUMC+));
* Previous major abdominal surgery or radiotherapy interfering with gastrointestinal 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 (Dr. Keszthelyi, Gastroenterologist MUMC+), who will decide on inor exclusion based upon the surgery applied;
* Use of medication potentially influencing gastrointestinal function and/or NCWS symptoms is allowed, provided that dosing has been stable for ≥ 1 month before enrolment;
* Administration of probiotic, 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 weight loss diet within the study period;
* Current malignancy;
* Pregnancy or breastfeeding;
* Participation in any scientific intervention study, which may interfere with this study;
* Insufficient fluency of the Dutch language.

Follow-up measurement - inclusion criteria

* (1) NCWS subject: develops GI symptoms within 12 hours after consumption of at least one of the study breads of study A or B (+15 mm on VAS); OR (2) Healthy control (sex matched to NCWS subjects): eats bread regularly (min. 5 days per week)
* Age between 18-70 years;
* Must have a fridge (4-7ºC) to shortly store the collected faecal sample.

Follow-up measurement - exclusion criteria in addition to the criteria listed above:

* Use of antibiotics during the 6 past months prior to faecal sampling;
* Healthy controls: developing GI symptoms after consumption of bread, or following a gluten-free or wheat-free

Primary outcomes:
measure: Overall GI symptom score
timeFrame: At the end of day 1, 2 and 3 of the run-in period, at the end of test day 1, 2 and 3, and at the end of the last three days of each wash-out period (so the three days prior to testday 2 and 3).
Secondary outcomes:
measure: Individual Intestinal symptom scores
timeFrame: At the end of day 1, 2 and 3 of the run-in period, at the end of test day 1, 2 and 3, and at the end of the last three days of each wash-out period (so the three days prior to testday 2 and 3).
measure: Individual Extra-intestinal symptom scores
timeFrame: At the end of day 1, 2 and 3 of the run-in period, at the end of test day 1, 2 and 3, and at the end of the last three days of each wash-out period (so the three days prior to testday 2 and 3).
measure: Average stool frequency and consistency
timeFrame: After every stool production during day 1, 2 and 3 of the run-in period, during test day 1, 2 and 3, and during the last three days of each wash-out period (so the three days prior to testday 2 and 3).
measure: Follow-up: microbiota composition
timeFrame: Follow-up measurement, within 1 year after completion of test day 3.
measure: Follow-up: microbiota activity
timeFrame: Follow-up measurement, within 1 year after completion of test day 3.
Other outcomes:
measure: Food intake by three-day food records
timeFrame: For 24 hours during day 1, 2 and 3 of the run-in period, during test day 1, 2 and 3, and during the last three days of each wash-out period (so the three days prior to test day 2 and 3).
measure: Participant characteristics in relation to NCWS
timeFrame: Data on medical history and demographic factors will be collected 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 run-in period.
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht University
city: Wageningen
country: Netherlands
facility: Wageningen University
Study officials:
affiliation: Maastricht University
name: Daisy MAE Jonkers, Prof., PhD
role: PRINCIPAL_INVESTIGATOR
References: