Tolerability of an Ancient Grain in Patients With Non-Celiac Wheat Sensitivity

NCT06191432 | Recruiting

• 1 other identifier: ACPM33
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

Patients suffering from wheat-related troubles, in absence of celiac disease or wheat allergy diagnosis, can suffer from non-celiac wheat sensitivity (NCWS). This is characterized by both gastrointestinal (GI) and extra-intestinal symptoms, which improve with the elimination of wheat intake. To date no definitive explanation of pathogenetic mechanisms of NCWS has been proved, and, similarly, no specific non-invasive diagnostic biomarker has been recognized. A real need of strict adherence to wheat-free diet (WFD) in NCWS has never been demonstrated. In this context, research is actively trying to find wheat varieties with absent or low immune-reactivity to be used for the treatment of NCWS patients. Preliminary evidence supports the assumption that diploid wheat species, as Triticum monococcum (TM), compared to common ones (Triticum aestivum (TA), could possess a lower immunogenic potential in NCWS patients. The first objective of our project is to verify whether the use of a diploid wheat (TM), with a lower concentrations and bioactivity of Amylase-Trypsin-Inhibitors (ATIs) and with gliadin proteins with a better digestibility, compared to a hexaploid one (TA) could improve both symptoms and quality of life (QoL) of NCWS subjects. The second objective is the identification of non-invasive serological biomarkers for NCWS diagnosis. The third objective is to identify T cell lymphocytes able to recognize cognate peptides from wheat proteins to better classify and monitor patients affected by NCWS. To achieve these results we planned a prospective, double-blind clinical trial with crossover, in which patients already diagnosed with NCWS (according to international criteria and with a double-blind placebo-controlled wheat challenge), following a strict WFD, will be exposed in double-blind to both TM and TA. All the patients will be evaluated clinically at the different timepoints with validated scales to assess tolerability of TM. Moreover, their intestinal permeability, immunological activation and gut microbiota patterns will be studied by both in vitro and in vivo techniques. Finally, a randomly chosen subset of patients will be studied through single cell transcriptome and T-cell receptor (TCR) sequencing on rectoscopy biopsy specimens to identify, T cell lymphocytes able to recognize cognate peptides from wheat proteins.

Conditions

Non-celiac Gluten Sensitivity

Keywords

Irritable Bowel Syndrome; Non-celiac wheat sensitivity; Triticum monococcum; Ancient grains

Outcome Measures

Primary Outcomes (3)

• Evaluation of gastrointestinal symptoms evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum

  A modified version of Gastrointestinal Symptom Rating Scale (GSRS) will be administered to all the patients during each outpatient visit to assess gastrointestinal symptoms before the challenge (T0, wheat free diet) and after exposure to both Triticum Monococcum (TM) and Triticum Aestivum (TA). Difference will be considered relevant if GSRS will be recorded \>30% compared to T0 and/or to any eventual increase determined during the administration of the other wheat variety.

  Days 0 (before start of challenge), 7 (after intake of first kind of flour according randomization) and 21 (after intake of second kind of flour according randomization)

• Evaluation of extraintestinal symptoms evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum

  A extraintestinal symptoms rating scale, based on the symptoms most frequently observed in NCWS patients, will be administered to all the patients during each outpatient visit to assess gastrointestinal symptoms before the challenge (T0, wheat free diet) and after exposure to both Triticum Monococcum (TM) and Triticum Aestivum (TA). Difference will be considered relevant if extraintestinal symptoms rating scale will be recorded \>30% compared to T0 and/or to any eventual increase determined during the administration of the other wheat variety.

  Days 0 (before start of challenge), 7 (after intake of first kind of flour according randomization) and 21 (after intake of second kind of flour according randomization)

• Evaluation of quality of life modification evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum

  The Irritable Bowel Syndrome-Quality of Life (IBS-QoL) will be used to assess patient's QoL. It is an already validated condition-specific tool for IBS patients, which incorporates specific subdomains, such as food avoidance, bowel habits, and the effect on the social/sexual relationships. IBS-QoL will be administered to all the patients during each outpatient visit to assess gastrointestinal symptoms before the challenge (T0, wheat free diet) and after exposure to both Triticum Monococcum (TM) and Triticum Aestivum (TA). Difference will be considered relevant if IBS-QoL will be recorded \>30% compared to T0 and/or to any eventual increase determined during the administration of the other wheat variety.

  Days 0 (before start of challenge), 7 (after intake of first kind of flour according randomization) and 21 (after intake of second kind of flour according randomization)

Secondary Outcomes (39)

• In vivo evaluation of intestinal permeability modification evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum

  Days 0 (before start of challenge), 7 (after intake of first kind of flour according randomization) and 21 (after intake of second kind of flour according randomization)

• Analysis of modification of serological indexes of intestinal permeability evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum: zonulin

  Days 0 (before start of challenge), 7 (after intake of first kind of flour according randomization) and 21 (after intake of second kind of flour according randomization)

• Analysis of modification of serological indexes of intestinal permeability evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum: occludin

  Days 0 (before start of challenge), 7 (after intake of first kind of flour according randomization) and 21 (after intake of second kind of flour according randomization)

• Analysis of modification of serological indexes of intestinal permeability evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum: claudin 1

  Days 0 (before start of challenge), 7 (after intake of first kind of flour according randomization) and 21 (after intake of second kind of flour according randomization)

• Analysis of modification of serological indexes of intestinal injury evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum: intestinal fatty acid-binding protein

  Days 0 (before start of challenge), 7 (after intake of first kind of flour according randomization) and 21 (after intake of second kind of flour according randomization)

Study Arms (2)

NCWS Packets A-B

EXPERIMENTAL

NCWS patients will undergo a Double-Blind Wheat Challenge DBWC with an ancient diploid wheat (TM) or a modern hexaploid wheat (TA). This DBWC will be performed with flour packets coded A or B, each containing respectively one of the wheat varieties. Packets A or B will be given for 1 week and then, after 1 week of washout (or until patients report complete well-being), the patients will receive the other packets for another 1 week (cross-over design).

Dietary Supplement: Administration of Triticum Monococcum flour; Dietary Supplement: Administration of Triticum Aestivum flour

NCWS Packets B-A

EXPERIMENTAL

NCWS patients will undergo a Double-Blind Wheat Challenge DBWC with an ancient diploid wheat (TM) or a modern hexaploid wheat (TA). This DBWC will be performed with flour packets coded A or B, each containing respectively one of the wheat varieties. Packets A or B will be given for 1 week and then, after 1 week of washout (or until patients report complete well-being), the patients will receive the other packets for another 1 week (cross-over design).

Dietary Supplement: Administration of Triticum Monococcum flour; Dietary Supplement: Administration of Triticum Aestivum flour

Interventions

Administration of Triticum Monococcum flour DIETARY_SUPPLEMENT

Patients will be administered a daily dose of 80g of flour of Triticum Monococcum (equivalent to 10g of gluten), which will be dissolved and cooked by the patients themselves. During the challenge, the severity of the symptoms will be recorded using a 10-points visual analog scale (VAS). The challenges will be stopped when clinical reactions will occur for at least 2 consecutive days (increase \>3 in VAS) for either GI or extraintestinal symptoms. Challenges will be considered positive if symptoms, which had been initially present, reappear after their disappearance on elimination diet, and if the GI and/or extraintestinal symptom's scores will be \>30% compared to any eventual increase determined during the administration of the other wheat variety.

NCWS Packets A-B; NCWS Packets B-A

Administration of Triticum Aestivum flour DIETARY_SUPPLEMENT

Patients will be administered a daily dose of 80g of flour of Triticum Aestivum (equivalent to 10g of gluten), which will be dissolved and cooked by the patients themselves. During the challenge, the severity of the symptoms will be recorded using a 10-points visual analog scale (VAS). The challenges will be stopped when clinical reactions will occur for at least 2 consecutive days (increase \>3 in VAS) for either GI or extraintestinal symptoms. Challenges will be considered positive if symptoms, which had been initially present, reappear after their disappearance on elimination diet, and if the GI and/or extraintestinal symptom's scores will be \>30% compared to any eventual increase determined during the administration of the other wheat variety.

NCWS Packets A-B; NCWS Packets B-A

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• age \>18 and \<65 years;
• negativity of class A (IgA) and G (IgG) immunoglobulin (Ig) anti-deamidated gliadin (anti-DGP); negativity of IgA and IgG anti-tissue transglutaminase (anti-tTG) and anti-endomysial antibodies (EMA) ;
• absence of intestinal villous atrophy, documented in all patients carrying the DQ2 and/or DQ8 human leukocyte antigen haplotypes (therefore regardless of the negativity of celiac disease-specific serum antibodies);
• absence of wheat allergy (negative prick test and/or serum IgE measurement specific to wheat, gluten and gliadin).

You may not qualify if:

• age \<18 and \>65 years;
• pregnancy;
• alcohol and/or drugs abuse;
• Helicobacter pylori and other bacterial and/or parasitic infections;
• diagnosis of chronic inflammatory intestinal diseases and other organic pathologies affecting the digestive system (for example, serious liver diseases), nervous system diseases, major psychiatric disorders, immunological deficits and impairments that limit physical activity;
• cancer
• patients undergoing chemotherapy and/or radiotherapy.

Sponsors & Collaborators

• University of Palermo: lead

Study Sites (1)

University Hospital of Palermo

Palermo, Sicily, 90127, Italy

RECRUITING

Related Publications (6)

• Schuppan D, Pickert G, Ashfaq-Khan M, Zevallos V. Non-celiac wheat sensitivity: differential diagnosis, triggers and implications. Best Pract Res Clin Gastroenterol. 2015 Jun;29(3):469-76. doi: 10.1016/j.bpg.2015.04.002. Epub 2015 May 8.

  PMID: 26060111 RESULT

• Carroccio A, Giannone G, Mansueto P, Soresi M, La Blasca F, Fayer F, Iacobucci R, Porcasi R, Catalano T, Geraci G, Arini A, D'Alcamo A, Villanacci V, Florena AM. Duodenal and Rectal Mucosa Inflammation in Patients With Non-celiac Wheat Sensitivity. Clin Gastroenterol Hepatol. 2019 Mar;17(4):682-690.e3. doi: 10.1016/j.cgh.2018.08.043. Epub 2018 Aug 21.

  PMID: 30138736 RESULT

• Dieterich W, Schuppan D, Schink M, Schwappacher R, Wirtz S, Agaimy A, Neurath MF, Zopf Y. Influence of low FODMAP and gluten-free diets on disease activity and intestinal microbiota in patients with non-celiac gluten sensitivity. Clin Nutr. 2019 Apr;38(2):697-707. doi: 10.1016/j.clnu.2018.03.017. Epub 2018 Apr 4.

  PMID: 29653862 RESULT

• 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.

  PMID: 29578652 RESULT

• Sofi F, Whittaker A, Gori AM, Cesari F, Surrenti E, Abbate R, Gensini GF, Benedettelli S, Casini A. Effect of Triticum turgidum subsp. turanicum wheat on irritable bowel syndrome: a double-blinded randomised dietary intervention trial. Br J Nutr. 2014 Jun 14;111(11):1992-9. doi: 10.1017/S000711451400018X. Epub 2014 Feb 13.

  PMID: 24521561 RESULT

• Seidita A, Mansueto P, Giuliano A, Chiavetta M, Mandreucci F, Soresi M, Pistone M, Compagnoni S, Castellucci D, Bisso G, Faraci F, Maestri S, Disclafani R, Sapone A, Fasano A, Carroccio A. Potential tolerability of ancient grains in non-celiac wheat sensitivity patients: A preliminary evaluation. Front Med (Lausanne). 2022 Sep 28;9:995019. doi: 10.3389/fmed.2022.995019. eCollection 2022.

  PMID: 36250065 RESULT

MeSH Terms

Conditions

Irritable Bowel Syndrome

Condition Hierarchy (Ancestors)

Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Study Officials

• Antonio Carroccio, MD

  University of Palermo

  STUDY CHAIR

Central Study Contacts

Pasquale Mansueto, MD

CONTACT

00390916554815; pasquale.mansueto@unipa.it

Aurelio Seidita, MD

CONTACT

00390916554815; aurelio.seidita@unipa.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Patients will be assigned by a computerized algorithm to start the challenge with the sachets containing triticum monococcum or triticum aestivum. At the end of the first challenge and after an adequate wash-out period, the patients will undergo crossover with the other type of wheat sachets. The sachets, called A or B, will be completely indistinguishable from each other both in terms of their organoleptic characteristics and the quantity of content (80g of flour) and in terms of their packaging. The company that will supply the flours will be the custodian of the randomization code, and the key will be provided to the experimenters only at the end of all the challenges.
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Prospective, randomized, double-blind, cross-over, single center clinical trials.

Study Record Dates

• First Submitted: December 20, 2023
• First Posted: January 5, 2024
• Study Start: February 1, 2024
• Primary Completion: July 31, 2025
• Study Completion (Estimated): November 30, 2026
• Last Updated: January 12, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)