Non-celiac Gluten SensitivityWoWNCT05779358
Gluten and (Extra-)Intestinal Symptoms in NCGS
A study testing Expectancy and gluten in people with Non-celiac Gluten Sensitivity, run by Maastricht University at 3 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Non-celiac Gluten Sensitivity
- What is being tested?
- Expectancy and gluten
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 84 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 19 Oct 2018to 15 Feb 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 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.
Who cannot join
- 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;
Show all 13Show fewer
- 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.
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
Netherlands2 sites
Maastricht University
Maastricht
Wageningen University
Wageningen
About this study
Official title: The Effects of Bread Consumption on Intestinal and Extra-intestinal Symptoms in Non-coeliac Gluten Sensitivity
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:
Read more
- 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-)
Read the 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
- Being tested
- Expectancy and gluten
- Keywords
- Non-Coeliac Gluten Sensitivity, NCGS, Gluten, Gastrointestinal symptoms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Expectancy and glutenOther
Effect of expectancy to receive gluten and/or actual gluten intake
| Study group | Role | What they receive |
|---|---|---|
| E+ G+ | Active comparator | Participants with the expectation of receiving gluten-containing bread and actually receiving gluten-containing oat bread during the test day. Receives: 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. Receives: 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. Receives: 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. Receives: Other: Expectancy and gluten |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
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.
Parameters: abdominal pain, abdominal discomfort, belching, bloating, flatulence, diarrhoea, constipation, urge to empty bowel, fullness, nausea.
Measured: 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)
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.
Parameters: tiredness, headache, foggy mind
Measured: 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)
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: 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)
Change from baseline. Mood is measured by the Positive and Negative Affective Schedule (PANAS) questionnaire.
Measured: Test day: baseline, every hour after breakfast (T = 1 hour until T = 8 hours)
Overall and individual gastrointestinal symptom score (long-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.
Parameters: overall gastrointestinal symtoms, abdominal pain, abdominal discomfort, belching, bloating, flatulence, diarrhoea, constipation, urge to empty bowel, fullness, nausea.
Measured: 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
Individual extra-intestinal symptom scores (long 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.
Parameters: tiredness, headache, foggy mind
Measured: 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
Average stool frequency and consistency (long term)
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: 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
Mood (long term)
Change from baseline. Mood is measured by the Positive and Negative Affective Schedule (PANAS) questionnaire.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2023
- Study start19 Oct 2018
- Primary completion31 Jan 2022
- Study completion15 Feb 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-celiac Gluten SensitivityStudies 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
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 84 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht University
- Sponsor type
- University, hospital or other
- Collaborators
- University of Leeds, Wageningen University
- Responsible party
- Sponsor
- Investigators
- Daisy MAE Jonkers, Prof, PhD, Principal investigator, Maastricht UniversityLouise Dye, Prof, PhD, Principal investigator, University of Leeds
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05779358
- Sponsor's protocol ID
- NL64850.068.18
- Other IDs
- METC183011
- Acronym
- WoW
- Status last verified
- Mar 2023
- First submitted
- 9 Mar 2023
- Last updated
- 22 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 38040019
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Bread Consumption on Intestinal and Extra-intestinal Symptoms in Non-coeliac Gluten Sensitivity
- ClinicalTrials.gov ID
- NCT05779358
- Acronym / sponsor ID
- WoW / NL64850.068.18
- Conditions
- Non-celiac Gluten Sensitivity
- Keywords
- Non-Coeliac Gluten Sensitivity, NCGS, Gluten, Gastrointestinal symptoms
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 84 participants (actual)
- Lead sponsor
- Maastricht UniversityUniversity, hospital or other
- Collaborators
- University of Leeds, Wageningen University
- Study start
- 19 Oct 2018 (actual)
- Primary completion
- 31 Jan 2022 (actual)
- Study completion
- 15 Feb 2022 (actual)
- First posted
- 22 Mar 2023 (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.
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-)
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| E+ G+ | Active comparator | Other: Expectancy and glutenParticipants with the expectation of receiving gluten-containing bread and actually receiving gluten-containing oat bread during the test day. |
| E+ G- | Active comparator | Other: Expectancy and glutenParticipants with the expectation of receiving gluten-containing bread, but actually receiving gluten-free oat bread during the test day. |
| E- G+ | Active comparator | Other: Expectancy and glutenParticipants with the expectation of receiving gluten-free bread but actually receiving gluten-containing oat bread during the test day. |
| E- G- | Placebo comparator | Other: Expectancy and glutenParticipants with the expectation of receiving gluten-free bread and actually receiving gluten-free oat bread during the test day. |
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 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.
Key exclusion criteria (13 listed)
- 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:
- Use of medication potentially influencing GI function and/or NCGS symptoms is allowed, provided that dosing has been stable for > 6 weeks before enrolment;
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 |
|---|---|---|
| Expectancy and glutenEffect of expectancy to receive gluten and/or actual gluten intake | Other | E+ G+, E+ G-, E- G+, E- G- |
Primary outcome
Overall gastrointestinal symptom score (short term)
Time frame: 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)
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.
8 secondary outcomes
Individual gastrointestinal symptom scores (short term)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: Test day: baseline, every hour after breakfast (T = 1 hour until T = 8 hours)
Overall and individual gastrointestinal symptom score (long-term)
Time frame: 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
Individual extra-intestinal symptom scores (long term)
Time frame: 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
Average stool frequency and consistency (long term)
Time frame: 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
Mood (long term)
Time frame: 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
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 22 Mar 2023.
- Derived from this study: PubMed 38040019de 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.
- Individual participant dataSharing planned: No
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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
Louise Dye, Prof, PhD principal investigator
University of Leeds
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Expectancy and gluten in people with Non-celiac Gluten Sensitivity, run by Maastricht University at 3 sites in 2 countries.
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 13 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 22 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 3 sites in Netherlands, United Kingdom. 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. Some participants in this study may receive a placebo. 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 gastrointestinal symptom score (short term) (time frame: 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)). 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 NCT05779358, 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 22 Mar 2023.