RECRUITINGINTERVENTIONAL

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

Tolerability of an Ancient Grain in Patients With Non-Celiac Wheat Sensitivity. A Clinical Study and a Search for Diagnostic Biomarkers.

About This Trial

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.

Who May Be Eligible (Plain English)

Who May Qualify: - 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). Who Should NOT Join This Trial: - age \<18 and \>65 years; - self-exclusion of gluten/wheat from the diet and refusal to reintroduce it, for diagnostic purposes, before entering the study; - 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. Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: * 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). Exclusion Criteria: * age \<18 and \>65 years; * self-exclusion of gluten/wheat from the diet and refusal to reintroduce it, for diagnostic purposes, before entering the study; * 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.

Treatments Being Tested

DIETARY_SUPPLEMENT

Administration of Triticum Monococcum flour

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.

DIETARY_SUPPLEMENT

Administration of Triticum Aestivum flour

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.

Locations (1)

University Hospital of Palermo

Palermo, Sicily, Italy