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Effects of Different Bread Types in NCGS (BREAD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04084470
Recruitment Status : Recruiting
First Posted : September 10, 2019
Last Update Posted : February 20, 2020
Sponsor:
Information provided by (Responsible Party):
Maastricht University

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 gluten/wheat sensitivity (NCGS/NCWS) is accompanied by a range of (extra-)intestinal complaints soon after consuming wheat or gluten, which improve after wheat/gluten 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 NCGS/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, gut microbiota composition and activity, metabolite profiles, and innate immune function in individuals with NCGS using a three-arm randomized cross-over design. Subjects are required to adhere to a gluten-free diet during the trial. The investigators hypothesize that grain type and processing will have a different effect on the primary outcomes.


Condition or disease Intervention/treatment Phase
Non-Coeliac Gluten Sensitivity (NCGS) Non-Coeliac Wheat Sensitivity (NCWS) Dietary Supplement: Different types of bread Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Three-arm randomized cross-over study
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Official Title: The Effects of the Different Bread Types of Fully Known Composition on Gastrointestinal Symptoms, Microbiota, and Metabolism in Individuals With Non-coeliac Gluten Sensitivity.
Actual Study Start Date : September 17, 2019
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : November 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Allergy

Arm Intervention/treatment
Active Comparator: Bread types 1 & 2
Daily consumption of 5 slices of allocated bread type for 3 consecutive days.
Dietary Supplement: Different types of bread
Three-arm randomized cross-over study. All subjects start with a run-in period of 3 days, thereafter they will receive two different types of bread in a randomized order for 3 consecutive days, with a wash-out period of 11 days in between. After each period, biological samples will be collected.

Active Comparator: Bread types 3 & 4
Daily consumption of 5 slices of allocated bread type for 3 consecutive days.
Dietary Supplement: Different types of bread
Three-arm randomized cross-over study. All subjects start with a run-in period of 3 days, thereafter they will receive two different types of bread in a randomized order for 3 consecutive days, with a wash-out period of 11 days in between. After each period, biological samples will be collected.

Active Comparator: Bread types 5 & 6
Daily consumption of 5 slices of allocated bread type for 3 consecutive days.
Dietary Supplement: Different types of bread
Three-arm randomized cross-over study. All subjects start with a run-in period of 3 days, thereafter they will receive two different types of bread in a randomized order for 3 consecutive days, with a wash-out period of 11 days in between. After each period, biological samples will be collected.




Primary Outcome Measures :
  1. Overall GI symptom score [ Time Frame: At the end of each day of the run-in period, both intervention periods and wash-out period day 9-11. ]
    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.


Secondary Outcome Measures :
  1. Individual Intestinal symptom scores [ Time Frame: At the end of each day of the run-in period, both intervention periods and wash-out period day 9-11. ]
    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.

  2. Individual Extra-intestinal symptom scores [ Time Frame: At the end of each day of the run-in period, both intervention periods and wash-out period day 9-11. ]
    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.

  3. Average stool frequency and consistency [ Time Frame: After every stool production during each day of the run-in period, both intervention periods and wash-out period day 9-11. ]
    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.

  4. Microbial composition and activity [ Time Frame: Oral microbiota and faeces samples will be collected at four time-points during the study: day 4 (morning after run-in), day 7 (morning after intervention period 1), day 18 (morning after wash-out, and day 21 (morning after intervention period 2). ]
    Oral and faecal microbiota composition and functional capacity will be assessed by characterizing of the full genetic microbial content by state-of-the-art next generation sequencing. Furthermore, metabolites of saccharolytic and proteolytic fermentation will be assessed.

  5. Exhaled Metabolite production [ Time Frame: Exhaled air will be collected at four time-points during the study: day 4 (morning after run-in), day 7 (morning after intervention period 1), day 18 (morning after wash-out, and day 21 (morning after intervention period 2). ]
    Volatile organic compounds in exhaled air will be measure by gas chromatography time-of flight mass spectrometry (GC-tof-MS).

  6. Immune parameters [ Time Frame: Blood and faecal samples will be collected at four time-points during the study: day 4 (morning after run-in), day 7 (morning after intervention period 1), day 18 (morning after wash-out, and day 21 (morning after intervention period 2). ]
    Immune parameters in serum (such as CRP, TNF-a, IL-1b, IL-6, IL-8) and feaces (such as sIgA, human beta defensin 2 (HBD2), calprotectin) will be measured. Furthermore, intestinal fatty acids binding protein (iFABP) will be measured in serum, as biomarker of intestinal cell damage.


Other Outcome Measures:
  1. Food intake by three-day food records [ Time Frame: Throughout each day of the run-in period, both intervention periods and wash-out period day 9-11. ]
    A three-day food record (on paper) to check for the adherence to the gluten-free diet.

  2. Participant characteristics in relation to NCGS [ Time Frame: 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. ]
    To characterise NCGS subjects, data will be collected on medical history (e.g. surgery, GI diseases, medication use, allergies), demographic (e.g. age, gender, educational background, BMI, smoking, alcohol use) and psychosocial factors (relating to e.g. anxiety, depression, somatisation) using screening questionnaires.

  3. Oral microbiota and protein analysis [ Time Frame: Oral microbiota and faeces samples will be collected at four time-points during the study: day 4 (morning after run-in), day 7 (morning after intervention period 1), day 18 (morning after wash-out, and day 21 (morning after intervention period 2). ]
    Explorative comparison of oral microbiota with faecal microbiota. Protein analysis relates to defence proteins (including e.g. IgA, lysozyme) and will be performed in line with faecal microbiota, looking at overall microbial structure (alpha- and beta diversity indices) and specific taxa.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Develops of self-reported GI symptoms after a single intake of bread or gluten- containing products;
  • Age between 18-70 years;
  • Avoiding or restricting gluten-containing foods for at least 1 week before start of as well as during the study (based on a gluten-free dietary compliance questionnaire of Biagi et al. (only group 2, 3 and 4 of the Biagi will be eligible);
  • 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 NCGS 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 NCGS symptoms is allowed, provided that dosing has been stable for ≥ 1 month before enrolment;
  • Use of antibiotics within 90 days prior to the study;
  • 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;
  • Use of immunosuppressive drugs within 90 days before enrolment;
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04084470


Contacts
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Contact: Marlijne CG de Graaf, MSc +31(0)433884237 m.degraaf@maastrichtuniversity.nl
Contact: Daisy MAE Jonkers, Prof., PhD +31(0)433884266 d.jonkers@maastrichtuniversity.nl

Locations
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Netherlands
Maastricht University Recruiting
Maastricht, Netherlands
Contact: Marlijne CG de Graaf, MSc    +31655741096    brood-intmed@maastrichtuniversity.nl   
Sponsors and Collaborators
Maastricht University
Investigators
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Principal Investigator: Daisy MAE Jonkers, Prof., PhD Maastricht University
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Responsible Party: Maastricht University
ClinicalTrials.gov Identifier: NCT04084470    
Other Study ID Numbers: NL67466.068.18
METC18-032 ( Other Identifier: METC azM/UM )
First Posted: September 10, 2019    Key Record Dates
Last Update Posted: February 20, 2020
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Maastricht University:
Non-Coeliac Gluten Sensitivity
Non-Coeliac Wheat Sensitivity
Gluten Sensitivity
Bread
Wheat
Gastrointestinal symptoms
Microbiota
Immune response
Gluten
Additional relevant MeSH terms:
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Hypersensitivity
Immune System Diseases