Wheat sensitivity and functional dyspepsia dietary trial and challenge protocol

Dietary trial Patient recruitment: Suitable patients who consent to dietary trial and who meet the eligibility criteria outlined below will be enrolled into the dietary trial. We will aim to recruit 50 patients with functional dyspepsia diagnosed according to the internationally accepted Rome III criteria. Initial clinical work up: The following information will be collected from all patients prior to the dietary trial if not already available from the medical record: - Serum sample for; a. FBC, CRP, ESR; b. tTG IgA, total IgA; c. HLA DQ2/8 status; d. anti-gliadin antibodies; e. wheat specific IgE; f. T cell subtype analysis - Demographic and medical information - Gastrointestinal symptoms from the phase 1 questionnaire (including nepean dyspepsia index, GI outpatient questionnaire, Rome III diagnostic questionnaire, IBS severity scoring system, hospital anxiety and depression scale, medication history) - Dietary history - Endoscopic and serum samples for immunological analysis - Stool sample for microbiome analysis For those who meet the inclusion and exclusion criteria will enter the dietary trial. The dietary trial is currently the only diagnostic test available for the diagnosis of non-coeliac gluten sensitivity, and this protocol is in accordance with the current international consensus guidelines. Intervention steps; 1. Dietitian and trained physician review at enrolment. Patient educated by dietitian on following a gluten free, low FODMAP diet - resources provided (Clinic visit) 2. Symptom assessment at baseline using the Nepean Dyspepsia Index, IBS SSS, outpatient GI questionnaire and wheat sensitivity questionnaire 3. Participants to follow this gluten free, low FODMAP diet for 4 weeks - compliance measured using food diary in weekly follow up sessions. Gluten free diet resource provided to al participants is consistent with Coeliac Society guidlines and low FODMAP diet resource consistent with MonashFODMAP guidleines. 4. Symptom assessment will be done weekly during the run in diet using the wheat sensitivity questionnaire 5. Overall compliance to be reviewed after 4 weeks using GFD scoring tool and using a food diary for the adherence to the FODMAP component of the diet (Visit 2, HMRI) 6. For those whose dyspeptic symptoms respond to the run in diet, defined as a greater than 30% response in dyspeptic symptoms as measured by the modified Salerno wheat sensitivity questionnaire at visit 2; a. Repeat serum testing of ESR and CRP b. Repeat serum testing for immunological analysis c. Repeat stool sample for microbiome analysis 7. These subjects will then proceed to move on to the dietary challenge stage: Double blind randomized placebo controlled crossover gluten and wheat challenge Cooked gluten and FODMAP will be administered in the form of a muesli bar (see 'food preparation') to be consumed as morning or afternoon tea daily while continuing gluten free, low FODMAP baseline diet a. FODMAP depleted gluten15 g/day (commercially available) b. High FODMAP, gluten free c. Placebo 10-15g/day (no FODMAP, no gluten) 8. Patient provided with labelled study food to be taken home and stored in the freezer for the duration of the trial (visit 2) 9. Each challenge will be for 1 week, with 1 week washout between each challenge (6 weeks total). The order in which participants receive the study food will be randomized. 10. Participants will receive a phone call during each dietary challenge week (ie. fortnightly) to ensure compliance and ascertain presence of adverse effects 11. Symptom assessment will be done daily throughout trial using the specific wheat sensitivity questionnaire developed for the study in a mobile app format (Qualtrix) or paper based questionnaire 12. Visit at the end of the trial (Visit 3, week 7-8) to discuss the response to the trial (gluten/ FODMAP sensitivity) Confirmation of food sensitivity In those with a positive response to gluten or FODMAP, they may be challenged again with the causative food along with placebo to confirm the presence of a food sensitivity, to overcome the high nocebo response previously reported in trials of this type. Study food preparation measures: Recipes made with only gluten free ingredients (other than the gluten bar) with FODMAP contents tested by accredited facility, and confirmed as low FODMAP (except high FODMAP bar). All bars made with the same base ingredients which are gluten free and low FODMAP. The high FODMAP bar includes added inulin to replace a proportiong of rice flour and the high gluten bar contains gluten flour to replace a proportion of rice flour. Food will be prepared by an accredited person who has been trained by the dietitian who developed the reciipes. Food will be labelled and vacuum packed and stored in a freezer for 3 months at a time. Participants will be instructed to store the study food in their home freezer during the trial. We anticipate that the dietary trial will yield four subsets of participants; i. Gluten responsive functional dyspepsia (ie. non-coeliac gluten sensitivity) ii. FODMAP responsive functional dyspepsia iii. Gluten and FODMAP responsive functional dyspepsia iv. Gluten and FODMAP unresponsive functional dyspepsia