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

Condition(s) studied

Investigational drug(s) / intervention(s)

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.

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.

Study 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.

Eligibility

Primary outcome measure(s)

• Evaluation of gastrointestinal symptoms 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)
  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.
• Evaluation of extraintestinal symptoms 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)
  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.
• Evaluation of quality of life 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)
  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.

Trial sites (1)

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