Clinical trial NCT05307185: Tritordeum-based Foods for IBS Symptoms
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Irritable Bowel Syndrome
Keywords: IBS
Diarrhea
Diet
FODMAPs
Tritordeum
Intestinal permeability
Symptoms
Dysbiosis
Gluten
Lead sponsor: Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de Bellis
Sponsor class: OTHER
First posted: 2022-04-01
Enrollment: 135
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multi-disciplinary, single-blind, parallel-group randomized controlled trial design
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in the total score of the irritable bowel syndrome - severity scoring system (IBS-SSS) questionnaire
timeFrame: Before the start of the study (time 0) and after 90 days of treatment (time 90).
Secondary outcomes:
measure: Change in the score of the single symptom items of the irritable bowel syndrome - severity scoring system (IBS-SSS) questionnaire
timeFrame: Before the start of the study (time 0) and after 90 days of treatment (time 90).
measure: Change in the psychological symptom profile evaluated by Symptom Checklist-90- Revised (SCL-90-R)
timeFrame: Before the start of the study (time 0) and after 90 days of treatment (time 90).
measure: Change in the intestinal permeabily parameters of sugar absorption test
timeFrame: Before the start of the study (time 0) and after 90 days of treatment (time 90).
measure: Change in the markers of integrity of the intestinal barrier
timeFrame: Before the start of the study (time 0) and after 90 days of treatment (time 90).
Other outcomes:
Locations:
city: Castellana Grotte
country: Italy
facility: IRCCS Saverio de Bellis
state: Bari
Study officials:
affiliation: National Institute for Digestive Diseases IRCCS " Saverio de Bellis"
name: Francesco Russo, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tuck CJ, Reed DE, Muir JG, Vanner SJ. Implementation of the low FODMAP diet in functional gastrointestinal symptoms: A real-world experience. Neurogastroenterol Motil. 2020 Jan;32(1):e13730. doi: 10.1111/nmo.13730. Epub 2019 Sep 30.
citation: Linsalata M, Riezzo G, Orlando A, D'Attoma B, Prospero L, Tutino V, Notarnicola M, Russo F. The Relationship between Low Serum Vitamin D Levels and Altered Intestinal Barrier Function in Patients with IBS Diarrhoea Undergoing a Long-Term Low-FODMAP Diet: Novel Observations from a Clinical Trial. Nutrients. 2021 Mar 21;13(3):1011. doi: 10.3390/nu13031011.
citation: Orlando A, Tutino V, Notarnicola M, Riezzo G, Linsalata M, Clemente C, Prospero L, Martulli M, D'Attoma B, De Nunzio V, Russo F. Improved Symptom Profiles and Minimal Inflammation in IBS-D Patients Undergoing a Long-Term Low-FODMAP Diet: A Lipidomic Perspective. Nutrients. 2020 Jun 2;12(6):1652. doi: 10.3390/nu12061652.
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citation: Rotondi Aufiero V, Fasano A, Mazzarella G. Non-Celiac Gluten Sensitivity: How Its Gut Immune Activation and Potential Dietary Management Differ from Celiac Disease. Mol Nutr Food Res. 2018 May;62(9):e1700854. doi: 10.1002/mnfr.201700854. Epub 2018 Apr 20.
citation: Barmeyer C, Schumann M, Meyer T, Zielinski C, Zuberbier T, Siegmund B, Schulzke JD, Daum S, Ullrich R. Long-term response to gluten-free diet as evidence for non-celiac wheat sensitivity in one third of patients with diarrhea-dominant and mixed-type irritable bowel syndrome. Int J Colorectal Dis. 2017 Jan;32(1):29-39. doi: 10.1007/s00384-016-2663-x. Epub 2016 Sep 30.
citation: Russo F, Riezzo G, Linsalata M, Orlando A, Tutino V, Prospero L, D'Attoma B, Giannelli G. Managing Symptom Profile of IBS-D Patients With Tritordeum-Based Foods: Results From a Pilot Study. Front Nutr. 2022 Feb 15;9:797192. doi: 10.3389/fnut.2022.797192. eCollection 2022.