Effects of Different Bread Types in NCGS

Overview

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.

Full Title of Study: “The Effects of the Different Bread Types of Fully Known Composition on Gastrointestinal Symptoms, Microbiota, and Metabolism in Individuals With Non-coeliac Gluten Sensitivity.”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Crossover Assignment
    • Primary Purpose: Basic Science
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: November 2020

Interventions

  • 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.

Arms, Groups and Cohorts

  • Active Comparator: Bread types 1 & 2
    • Daily consumption of 5 slices of allocated bread type for 3 consecutive days.
  • Active Comparator: Bread types 3 & 4
    • Daily consumption of 5 slices of allocated bread type for 3 consecutive days.
  • Active Comparator: Bread types 5 & 6
    • Daily consumption of 5 slices of allocated bread type for 3 consecutive days.

Clinical Trial Outcome Measures

Primary Measures

  • 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 Measures

  • 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.
  • 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.
  • 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.
  • 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.
  • 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).
  • 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.

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 70 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Maastricht University
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Daisy MAE Jonkers, Prof., PhD, Principal Investigator, Maastricht University
  • Overall Contact(s)
    • Marlijne CG de Graaf, MSc, +31(0)433884237, m.degraaf@maastrichtuniversity.nl

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.