Tritordeum-based Foods for IBS Symptoms

Study Overview
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Brief Summary
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People with irritable bowel syndrome (IBS), especially those with diarrhea (IBS-D), often describe worsening symptoms after eating certain foods. A structured dietary approach may represent a reliable strategy to improve their symptoms. In this framework, the diet low in oligosaccharides, disaccharides, monosaccharides, and fermentable polyols (FODMAPs - LFD) has been demonstrated to mitigate symptoms and reduce inflammatory status, increase vitamin D content, and affect the lipidomic profile. Unfortunately, adherence to LFD can be somewhat problematic, needing continuous nutritional support. Other dietary approaches with putative beneficial effects have been proposed to overcome these limitations. Among them, Tritordeum-based foods (TBD, bread, bakery products, and pasta) in substitution of other cereals seem to achieve promising results. TBD may represent a valid alternative, with high palatability, especially among Italian patients for whom pasta is considered one of the main assets of dietetic culture and easier to manage in their daily habits. Given these premises, this study aims to evaluate, in a randomized single-blinded controlled trial, the effects of 12-weeks of TBD compared with LFD and dietary advice of the same duration in improving the symptom profile well as the intestinal permeability and reducing putative dysbiosis of IBS-D patients. Along with the clinical study, an evaluation of gluten and proteomic composition will be performed to examine more in detail the intrinsic characteristics of Tritordeum.

Detailed Description
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A structured dietary approach could represent a reliable alternative strategy to treat patients with functional gastrointestinal disorders such as irritable bowel syndrome (IBS), mainly in its diarrhea variant (IBS-D). It is now well established that many people with IBS often describe worsening symptoms eating certain foods, such as those containing fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs). These short-chain carbohydrates are present in some foods, including wheat and beans. They may contribute to different digestive symptoms such as bloating, abdominal pain, and diarrhea due to poor absorption in the small intestine. In this way, FODMAPs are digested by colonic bacteria, releasing gas in the colon. Furthermore, FODMAPs can act as osmotic agents, increasing the water volume in the stool. In the last years, our group has focused research on the properties of a low FODMAPs diet (LFD) in the clinical management of patients with IBS-D, demonstrating that these patients benefit from a 12 weeks-LFD in mitigating the symptoms, reducing the inflammatory status, increasing the vitamin D content, and affecting the lipidomic profile. Unfortunately, adherence to LFD can be somewhat problematic, needing continuous nutritional support. Actually, alternative dietary approaches for these disorders may be hypothesized. It is now well established that, beyond non-celiac wheat sensitivity (NCWS), many individuals suffering from IBS-D or generical gluten-related disorders and mainly complainIng of abdominal bloating seem to benefit from removing wheat from the diet. The multifaceted setting of nutrients in wheat-based foods, other than gluten, could account for the different IBS symptoms. It has already been postulated that some monococcal diploid grain lines, with minimal activation of the innate immunity and a reduced amount of toxic gluten peptides, could be helpful for IBS-D patients. Among them, alternative grains such as Tritordeum seem to achieve good results. Tritordeum is a cereal derived from durum wheat and wild barley hybridization. Originally cultivated with traditional techniques in Spain, it has more recently grown in Apulia, a southern Italy region. Tritordeum grows well with little care, even in adverse conditions. Noteworthy, this cereal has significantly lower levels of gliadins, fewer carbohydrates and fructans, and a higher content of dietary fibers, proteins, and antioxidants than classic wheat. However, the presence of gluten makes this cereal not suitable for celiac patients. Thus, cereals such as Tritordeum, once further characterized in their proteomic profile and gluten composition, could offer opportunities for an innovative nutritional approach for patients suffering from IBS and, more in general, wheat-related disorders. Our group recently performed a pilot study to investigate the effects of a 12-week diet with Tritordeum-based foods (bread, bakery products, and pasta) in substitution of other cereals on the GI symptoms and the status of the GI barrier in IBS-D patients. This diet proved to reduce the patients' symptoms by affecting intestinal permeability significantly. The purpose of this study is to evaluate, in a randomized controlled trial, the beneficial effects of 12-weeks of TBD compared with LFD or specific advice for IBS of the same duration in improving the symptom profile of IBS-D patients.

Official Title
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A Comparison Among the Effects of the Low FODMAP Diet, a Tritordeum Based Diet, and Dietary Advice on the Gastrointestinal Symptom Profile in Patients With Irritable Bowel Syndrome-Diarrhea Variant (IBS-D): a Randomized Controlled Trial

Conditions
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Irritable Bowel Syndrome

Intervention / Treatment
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* Dietary Supplement: Tritordeum-based food


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Rome IV criteria for IBS diarrhea variant (IBS-D). Low-lactose diet is allowed, provided that patients agree to keep this intake constant throughout the study period, except in the case of randomization in the treatment arm with a low-FODMAPs diet. The use of probiotic products is permitted, and patients who consume probiotic products must be instructed to continue taking the same amount previously taken throughout the study period. The drugs used to treat IBS, including antidepressants, will be admitted provided they are used regularly and have a stable dosage for at least one month prior to inclusion in the study. Patients must be willing to change their current diet to participate in the study for the whole study period. Exclusion Criteria: Serious cardiac, hepatic, neurological or psychiatric diseases. GI diseases other than IBS (e.g., inflammatory bowel disease, celiac disease) that could explain current symptoms. Patients who previously had a low-content diet of particular substances (for example, low FODMAPs content, vegan diet, a gluten-free diet). - This last category of subjects will be able to return to the study provided they suspend the gluten-free diet until the symptoms reappear.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multi-disciplinary, single-blind, parallel-group randomized controlled trial design
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tritordeum-based Food (TBD)<br>A controlled TBD will be provided to each patient. The daily menu will be breakfast, mid-morning snacks, lunch, afternoon snacks, and dinner. This intervention diet implies that each patient in the study has to consume flour, bread, breakfast biscuits, taralli, and pasta prepared exclusively with Tritordeum. The diets will be designed by matching basal metabolism and daily energy consumption with anthropometric data of all patients to assign suitable and tailored dietary regimens. The software utilized to assess the daily intake of macronutrients (50% carbohydrates, 30% lipids, and 20% proteins) will be the same as LFD. | Dietary Supplement: Tritordeum-based food<br>* Diets will last 12 weeks with intermediate nutritional checks every four weeks before returning to the final study visit.<br>|
| Active Comparator: Low-FODMAPs diet (LFD)<br>A personalized LFD will be assigned after reviewing a food diary and having a one-on-one personal consultation with a nutritionist. Diet will match the basal metabolic rate and daily energy expenditure. A detailed weekly structured menu based on three meals (breakfast, lunch, and dinner) and two snacks (morning and afternoon) will be provided. Patients also will receive a booklet detailing what foods are allowed, which foods to avoid and which foods to reduce based on the classifications used by Monash University and cut-off values for each FODMAPs subgroup. Nutritionists have already created a leaflet for patients in the study with details on where to buy specific products. Besides, nutritionists will guarantee adequate fiber intake, also offering advice on cooking without onions and garlic and other high-FODMAP foods. Drinking alcohol will not be recommended, although it is not high in FODMAPs. | Dietary Supplement: Tritordeum-based food<br>* Diets will last 12 weeks with intermediate nutritional checks every four weeks before returning to the final study visit.<br>|
| Active Comparator: Specific dietary advice for IBS<br>According to NICE BDA Irritable bowel syndrome dietary advice, a controlled diet will be provided. All the food items (bread, pasta, taralli - local salty biscuits, and breakfast biscuits) will be prepared using durum wheat flour commercially available and anonymized to guarantee masking. Dietary recommendations include eating slowly, limiting alcohol, spicy food and fatty foods, caffeine, carbonated drinks; avoiding chewing gums and sweeteners containing polyols; small and frequent meals, stressful conditions. | Dietary Supplement: Tritordeum-based food<br>* Diets will last 12 weeks with intermediate nutritional checks every four weeks before returning to the final study visit.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the total score of the irritable bowel syndrome - severity scoring system (IBS-SSS) questionnaire | IBS-SSS contains 5 specific questions with instructions on how to score them. Each of the five questions (pain severity, pain frequency, abdominal distension severity, bowel movement satisfaction, quality of life) ranges from 0 to a maximum score of 100 using a visual analog scale (VAS), leading to a total possible score of 500. The primary outcome corresponds to a change in the total score of the IBS-SSS questionnaire at the end of the treatment period compared to baseline, and the proportion of patients who will achieve a difference in the total symptom score of IBS-SSS ≥50 after diet. Such difference is considered a significant clinical improvement. | Before the start of the study (time 0) and after 90 days of treatment (time 90). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the score of the single symptom items of the irritable bowel syndrome - severity scoring system (IBS-SSS) questionnaire | IBS-SSS contains 5 specific questions with instructions on how to score them. Each of the five questions (pain severity, pain frequency, abdominal distension severity, bowel movement satisfaction, quality of life) ranges from 0 to a maximum score of 100 using a visual analog scale (VAS). The secondary outcome is the measure of the effects of the dietary interventions on the individual symptom items score of IBS-SSS, as well as on the characteristics of the stool habit through the administration of the diaries. | Before the start of the study (time 0) and after 90 days of treatment (time 90). | 
| Change in the psychological symptom profile evaluated by Symptom Checklist-90- Revised (SCL-90-R) | The Symptom Checklist-90- Revised (SCL-90-R) questionnaire is one of the best-known and most used self-report measures in the psychopathological field. SCL-90-R evaluates a broad spectrum of psychopathological symptoms, namely nine primary symptom dimensions and three global indices. Only the Global Severity Index (GSI), the best indicator of the current intensity of psychic distress perceived by the subject will be considered. The raw scores will be transformed into T scores, and the T scores equal to or above 63 will be considered indicative of clinically significant symptomatology. | Before the start of the study (time 0) and after 90 days of treatment (time 90). | 
| Change in the intestinal permeabily parameters of sugar absorption test | For the evaluation of intestinal permeability, a test solution is prepared with 40 g sucrose (Su), 10 g lactulose (La) and 5 g mannitol (Ma) dissolved in 100 ml of water. The participants drink the test solution in the morning after an overnight fast, and all urine samples are collected for the subsequent 5 h. Urine samples were stored at -80°C until analysis. The detection and measurement of the three sugar probes, Su, La, and Ma in urine are performed by high-performance anion-exchange chromatography coupled with pulsed amperometric detection. Su, La, and Ma will be expressed as the percentage of excretion of the ingested amount of sugars. La and Ma measurements will then be reported as a ratio (La/Ma) to evaluate the permeability of the small intestinal tract. | Before the start of the study (time 0) and after 90 days of treatment (time 90). | 
| Change in the markers of integrity of the intestinal barrier | To evaluate intestinal barrier markers, blood samples are collected in ice chilled tubes containing Aprotinin and EDTA. The separated plasma are stored at -70 °C until assay. Serum levels of zonulin, IFABp, DAO, copeptin, meteorin, somatostatin and serotonin, are measured by enzyme immunoassay technique using commercial kits before and after the dietary interventions. All these parameters provide information about the state of health of the intestinal mucosa and will be expressed as ng/ml. | Before the start of the study (time 0) and after 90 days of treatment (time 90). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IBS, Diarrhea, Diet, FODMAPs, Tritordeum, Intestinal permeability, Symptoms, Dysbiosis, Gluten