Non-Coeliac Wheat Sensitivity (NCWS)BREADNCT04084470

Effects of Different Bread Types in NCWS

A study testing Different types of bread in people with Non-Coeliac Wheat Sensitivity (NCWS), run by Maastricht University at 2 sites in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Non-Coeliac Wheat Sensitivity (NCWS)
What is being tested?: Different types of bread
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 40 participants
Where: 2 sitesNetherlands
Study dates: 17 Sep 2019to 20 Dec 2022
Phase: Interventional
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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;

Show all 19Show fewer

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

Trial locations and contacts

2 sites in 1 country.

Netherlands2 sites

Maastricht University
Maastricht
Wageningen University
Wageningen

Other trials in Netherlands

About this study

Official title: The Effects of the Different Bread Types of Fully Known Composition on Gastrointestinal Symptoms in Individuals With Non-coeliac Wheat Sensitivity.

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.

Conditions: Non-Coeliac Wheat Sensitivity (NCWS)
Being tested: Different types of bread
Keywords: Non-Coeliac Wheat Sensitivity, Wheat Sensitivity, Bread, Wheat, Gastrointestinal symptoms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Different types of breadDietary supplement
Two studies comprising a double-blind randomized cross-over study. All subjects start with a run-in period of 3 days, thereafter they will receive three different types of bread in a randomized order for 1 day each, with a wash-out period of at least 7 days in between. Before test days 2 and 3, there is also a run-in period of three days.

Study groups in NCT04084470
Study group	Role	What they receive
Bread types 1, 2 and 3	Active comparator	Daily consumption of 5 slices of allocated bread type for three intervention days (separated by a wash-out period of at least 7 days). Receives: Dietary Supplement: Different types of bread
Bread types 4, 5 and 6	Active comparator	Daily consumption of 5 slices of allocated bread type for three intervention days (separated by a wash-out period of at least 7 days). Receives: Dietary Supplement: Different types of bread

What is being measured

The primary outcome is the main question the study is designed to answer.

Overall GI symptom score
Change from baseline, measured on the Visual Analogue Scale ranged from 0 - 100, in which 0 is absence of symptoms and 100 is severe symptoms.
Measured: 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 (5)

Individual Intestinal symptom scores
Change from baseline, measured on the Visual Analogue Scale ranged from 0 - 100, in which 0 is absence of symptoms and 100 is severe symptoms. Parameters: abdominal pain, abdominal discomfort, belching, bloating, flatulence, diarrhoea, constipation, urge to empty bowel, fullness, nausea.
Measured: 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).
Individual Extra-intestinal symptom scores
Change from baseline, measured on the Visual Analogue Scale ranged from 0 - 100, in which 0 is absence of symptoms and 100 is severe symptoms. Parameters: tiredness, headache, joint pains, confusion, loss of coordination, skin rash.
Measured: 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).
Average stool frequency and consistency
Bristol Stool Scale, a validated scale for faecal frequency and consistency, by classifying faeces into seven groups. Type 1: separate hard lumps, like nuts (hard to pass); Type 2: sausage-shaped but lumpy; Type 3: Like a sausage but with cracks on its surface; Type 4: Like a sausage or snake, smooth and soft; Type 5: Soft blobs with clear-cut edges (passed easily); Type 6: fluffy pieces with ragged edges, a mushy stool; Type 7: watery, no solid pieces / entirely liquid. Type 1-2 indicate constipation, type 3-4 are ideal stools as they are easier to pass, and type 5-7 may indicate diarrhoea and urgency.
Measured: 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).
Follow-up: microbiota composition
After completion of the primary study, 5 responders (see in- and exclusion criteria) will be included for a follow-up measurement. For comparison, 5 healthy controls will be included. The participants will collect one fecal sample at home. These samples will be used to study the effect of the six different bread types on microbiota composition in an in vitro fermentation model.
Measured: Follow-up measurement, within 1 year after completion of test day 3.
Follow-up: microbiota activity
After completion of the primary study, 5 responders (see in- and exclusion criteria) will be included for a follow-up measurement. For comparison, 5 healthy controls will be included. The participants will collect one fecal sample at home. These samples will be used to study the effect of the six different bread types on microbiota activity, measured by the release of microbial VOCs, in an in vitro fermentation model.
Measured: Follow-up measurement, within 1 year after completion of test day 3.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

17 Sep 201920 Dec 2022

First posted10 Sep 2019
Study start17 Sep 2019
Primary completion20 Dec 2022
Study completion20 Dec 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Non-Coeliac Wheat Sensitivity (NCWS)Studies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Model description: Double-blind randomized cross-over study
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 40 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04084470
Sponsor's protocol ID: NL67466.068.18
Other IDs: METC18-032
Acronym: BREAD
Status last verified: Mar 2023
First submitted: 20 Aug 2019
Last updated: 28 Mar 2023
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

de Graaf MC, Timmers E, Bonekamp B, van Rooy G, Witteman BJ, Shewry PR, Lovegrove A, America AH, Gilissen LJ, Keszthelyi D, Brouns FJ, Jonkers DMAE. Two randomized crossover multicenter studies investigating gastrointestinal symptoms after bread consumption in individuals with noncoeliac wheat sensitivity: do wheat species and fermentation type matter? Am J Clin Nutr. 2024 Apr;119(4):896-907. doi: 10.1016/j.ajcnut.2024.02.008. Epub 2024 Feb 18.
PubMed 38373694

Study at a glance

From the registry record, last updated by the sponsor on 28 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: The Effects of the Different Bread Types of Fully Known Composition on Gastrointestinal Symptoms in Individuals With Non-coeliac Wheat Sensitivity.
ClinicalTrials.gov ID: NCT04084470
Acronym / sponsor ID: BREAD / NL67466.068.18
Conditions: Non-Coeliac Wheat Sensitivity (NCWS)
Keywords: Non-Coeliac Wheat Sensitivity, Wheat Sensitivity, Bread, Wheat, Gastrointestinal symptoms
Study type: Interventional
Recruitment status: Completed
Enrolment: 40 participants (actual)
Lead sponsor: Maastricht UniversityUniversity, hospital or other
Collaborators: Wageningen University
Study start: 17 Sep 2019 (actual)
Primary completion: 20 Dec 2022 (actual)
Study completion: 20 Dec 2022 (actual)
First posted: 10 Sep 2019 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 2
Model description: Double-blind randomized cross-over study

Arm	Type	Receives
Bread types 1, 2 and 3	Active comparator	Dietary Supplement: Different types of breadDaily consumption of 5 slices of allocated bread type for three intervention days (separated by a wash-out period of at least 7 days).
Bread types 4, 5 and 6	Active comparator	Dietary Supplement: Different types of breadDaily consumption of 5 slices of allocated bread type for three intervention days (separated by a wash-out period of at least 7 days).

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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.

Key exclusion criteria (19 listed)

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:
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;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Different types of breadTwo studies comprising a double-blind randomized cross-over study. All subjects start with a run-in period of 3 days, thereafter they will receive three different types of bread in a randomized order for 1 day each, with a wash-out period of at least 7 days in between. Before test days 2 and 3, there is also a run-in period of three days.	Dietary supplement	Bread types 1, 2 and 3, Bread types 4, 5 and 6

Primary outcome

Overall GI symptom score
Time frame: 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).
Change from baseline, measured on the Visual Analogue Scale ranged from 0 - 100, in which 0 is absence of symptoms and 100 is severe symptoms.

5 secondary outcomes

Individual Intestinal symptom scores
Time frame: 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).
Individual Extra-intestinal symptom scores
Time frame: 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).
Average stool frequency and consistency
Time frame: 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).
Follow-up: microbiota composition
Time frame: Follow-up measurement, within 1 year after completion of test day 3.
Follow-up: microbiota activity
Time frame: Follow-up measurement, within 1 year after completion of test day 3.

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2023.
Derived from this study: PubMed 38373694de Graaf MC, Timmers E, Bonekamp B, van Rooy G, Witteman BJ, Shewry PR, Lovegrove A, America AH, Gilissen LJ, Keszthelyi D, Brouns FJ, Jonkers DMAE. Two randomized crossover multicenter studies investigating gastrointestinal symptoms after bread consumption in individuals with noncoeliac wheat sensitivity: do wheat species and fermentation type matter? Am J Clin Nutr. 2024 Apr;119(4):896-907. doi: 10.1016/j.ajcnut.2024.02.008. Epub 2024 Feb 18.
Individual participant dataSharing planned: No

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Daisy MAE Jonkers, Prof., PhD principal investigator

Maastricht University

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Different types of bread in people with Non-Coeliac Wheat Sensitivity (NCWS), run by Maastricht University at 2 sites in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall GI symptom score (time frame: 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).). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04084470, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Mar 2023.