Non-celiac Gluten Sensitivity Clinical Trial
Official title:
Tolerability of an Ancient Grain in Patients With Non-Celiac Wheat Sensitivity. A Clinical Study and a Search for Diagnostic Biomarkers.
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.
Status | Recruiting |
Enrollment | 68 |
Est. completion date | November 30, 2025 |
Est. primary completion date | July 31, 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 65 Years |
Eligibility | 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. |
Country | Name | City | State |
---|---|---|---|
Italy | University Hospital of Palermo | Palermo | Sicily |
Lead Sponsor | Collaborator |
---|---|
University of Palermo |
Italy,
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 G — View Citation
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) — View 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. — View Citation
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. — View Citation
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 sensi — View Citation
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 — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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) | |
Primary | 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) | |
Primary | 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 | In vivo evaluation of intestinal permeability modification evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum | In vivo evaluation of intestinal permeability will be performed using the Lactulose/Mannitol (La/Ma) ratio test, which has already been validated for gluten-related disorders, and other GI diseases with diarrhea and malabsorption. The test is based on the oral administration (after 12 hours of fasting) of an aqueous isosmolar solution (270mOsm) of 2 non-absorbable sugars (5g lactulose and 2g mannitol), in 150ml of water. Not being metabolizable, the 2 sugars are filtered by the kidneys and found in the urine; a urine collection for 5 hours after the bolus contains everything that has been filtered, with a La/Ma ratio <0.035, which is considered the "normal" intestinal permeability index (values =0.035 will be considered as index of increased GI permeability).
La/Ma ratio difference will be considered relevant for p<0.05 compared to T0 values and/or to the values 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 | Analysis of modification of serological indexes of intestinal permeability evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum: zonulin | Zonulin dosage will be performed by commercial ELISA kits according to the manufacturer's instructions.
Zonulin values difference will be considered relevant for p<0.05 compared to values registered at T0 and/or to the values 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 | Analysis of modification of serological indexes of intestinal permeability evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum: occludin | Occludin dosage will be performed by commercial ELISA kits according to the manufacturer's instructions.
Occludin values difference will be considered relevant for p<0.05 compared to values registered at T0 and/or to the values 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 | Analysis of modification of serological indexes of intestinal permeability evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum: claudin 1 | Claudin 1 dosage will be performed by commercial ELISA kits according to the manufacturer's instructions.
Claudin 1 values difference will be considered relevant for p<0.05 compared to values registered at T0 and/or to the values 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 | Analysis of modification of serological indexes of intestinal injury evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum: intestinal fatty acid-binding protein | intestinal fatty acid-binding protein dosage will be performed by commercial ELISA kits according to the manufacturer's instructions.
intestinal fatty acid-binding protein values difference will be considered relevant for p<0.05 compared to values registered at T0 and/or to the values 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 | Analysis of modification of serological indexes of intestinal injury evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum: lipopolysaccharide | lipopolysaccharide dosage will be performed by commercial ELISA kits according to the manufacturer's instructions.
lipopolysaccharide values difference will be considered relevant for p<0.05 compared to values registered at T0 and/or to the values 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 | Analysis of modification of serological indexes of intestinal injury evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum: lipopolysaccharide binding-protein | lipopolysaccharide binding-protein dosage will be performed by commercial ELISA kits according to the manufacturer's instructions.
lipopolysaccharide binding-protein values difference will be considered relevant for p<0.05 compared to values registered at T0 and/or to the values 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 | Analysis of modification of serological indexes of intestinal injury evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum: F-actin immunoglobulin (Ig)A | F-actin immunoglobulin (Ig)A dosage will be performed by commercial ELISA kits according to the manufacturer's instructions.
F-actin immunoglobulin (Ig)A values difference will be considered relevant for p<0.05 compared to values registered at T0 and/or to the values 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 | Analysis of modification of serological indexes of intestinal injury evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum: F-actin immunoglobulin (Ig)G | F-actin immunoglobulin (Ig)G dosage will be performed by commercial ELISA kits according to the manufacturer's instructions.
F-actin immunoglobulin (Ig)G values difference will be considered relevant for p<0.05 compared to values registered at T0 and/or to the values 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 | Analysis of modification of gut hypersensitivity indexes evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum: eosinophil cationic protein | Eosinophil cationic protein dosage will be performed on stool samples following already validated methodologies.
Eosinophil cationic protein values difference will be considered relevant for p<0.05 compared to values registered at T0 and/or to the values 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 | Analysis of modification of gut hypersensitivity indexes evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum: tryptase | Tryptase dosage will be performed on stool samples following already validated methodologies.
Tryptase values difference will be considered relevant for p<0.05 compared to values registered at T0 and/or to the values 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 | Analysis of modification of gut hypersensitivity indexes evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum: substance P | Substance P dosage will be performed on blood samples by commercial ELISA kits according to the manufacturer's instructions.
Substance P values difference will be considered relevant for p<0.05 compared to values registered at T0 and/or to the values 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 | Analysis of modification of gut hypersensitivity indexes evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum: somatostatin | Somatostatin dosage will be performed on blood samples by commercial ELISA kits according to the manufacturer's instructions.
Somatostatin values difference will be considered relevant for p<0.05 compared to values registered at T0 and/or to the values 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 | Analysis of modification of gut hypersensitivity indexes evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum: serotonin | Serotonin dosage will be performed on blood samples by commercial ELISA kits according to the manufacturer's instructions.
Serotonin values difference will be considered relevant for p<0.05 compared to values registered at T0 and/or to the values 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 | Analysis of modification of gut hypersensitivity indexes evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum: vasoactive intestinal peptide | Vasoactive intestinal peptide dosage will be performed on blood samples by commercial ELISA kits according to the manufacturer's instructions.
Vasoactive intestinal peptide values difference will be considered relevant for p<0.05 compared to values registered at T0 and/or to the values 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 | Analysis of modification of the humoral immune response to gluten evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum: anti-gliadin antibodies immunoglobulin A | Humoral immune response to gluten will be evaluated by dosing plasmatic levels of anti-gliadin antibodies immunoglobulin A by commercial ELISA assays, following manufacturer's instructions.
Anti-gliadin antibodies immunoglobulin A values difference will be considered relevant for p<0.05 compared to values registered at T0 and/or to the values 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 | Analysis of modification of the humoral immune response to gluten evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum: anti-gliadin antibodies immunoglobulin G | Humoral immune response to gluten will be evaluated by dosing plasmatic levels of anti-gliadin antibodies immunoglobulin G by commercial ELISA assays, following manufacturer's instructions.
Anti-gliadin antibodies immunoglobulin G values difference will be considered relevant for p<0.05 compared to values registered at T0 and/or to the values 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 | Analysis of modification of the serological inflammatory biomarkers evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum: granulocyte colony-stimulating factor | Expression of serological inflammatory biomarkers will be evaluated, on all the samples collected, by multiplexing simultaneous analysis with high sensitivity microsphere-based assays or ELISA.
Granulocyte colony-stimulating factor values difference will be considered relevant for p<0.05 compared to values registered at T0 and/or to the values 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 | Analysis of modification of the serological inflammatory biomarkers evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum: granulocyte-macrophage colony-stimulating factor | Expression of serological inflammatory biomarkers will be evaluated, on all the samples collected, by multiplexing simultaneous analysis with high sensitivity microsphere-based assays or ELISA.
Granulocyte-macrophage colony-stimulating factor values difference will be considered relevant for p<0.05 compared to values registered at T0 and/or to the values 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 | Analysis of modification of the serological inflammatory biomarkers evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum: interferon (IFN)-? | Expression of serological inflammatory biomarkers will be evaluated, on all the samples collected, by multiplexing simultaneous analysis with high sensitivity microsphere-based assays or ELISA.
Interferon (IFN)-? values difference will be considered relevant for p<0.05 compared to values registered at T0 and/or to the values 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 | Analysis of modification of the serological inflammatory biomarkers evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum: interleukin (IL)-1ß | Expression of serological inflammatory biomarkers will be evaluated, on all the samples collected, by multiplexing simultaneous analysis with high sensitivity microsphere-based assays or ELISA.
interleukin (IL)-1ß values difference will be considered relevant for p<0.05 compared to values registered at T0 and/or to the values 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 | Analysis of modification of the serological inflammatory biomarkers evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum: interleukin (IL)-2 | Expression of serological inflammatory biomarkers will be evaluated, on all the samples collected, by multiplexing simultaneous analysis with high sensitivity microsphere-based assays or ELISA.
interleukin (IL)-2 values difference will be considered relevant for p<0.05 compared to values registered at T0 and/or to the values 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 | Analysis of modification of the serological inflammatory biomarkers evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum: interleukin (IL)-4 | Expression of serological inflammatory biomarkers will be evaluated, on all the samples collected, by multiplexing simultaneous analysis with high sensitivity microsphere-based assays or ELISA.
interleukin (IL)-4 values difference will be considered relevant for p<0.05 compared to values registered at T0 and/or to the values 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 | Analysis of modification of the serological inflammatory biomarkers evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum: interleukin (IL)-5 | Expression of serological inflammatory biomarkers will be evaluated, on all the samples collected, by multiplexing simultaneous analysis with high sensitivity microsphere-based assays or ELISA.
interleukin (IL)-5 values difference will be considered relevant for p<0.05 compared to values registered at T0 and/or to the values 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 | Analysis of modification of the serological inflammatory biomarkers evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum: interleukin (IL)-6 | Expression of serological inflammatory biomarkers will be evaluated, on all the samples collected, by multiplexing simultaneous analysis with high sensitivity microsphere-based assays or ELISA.
interleukin (IL)-6 values difference will be considered relevant for p<0.05 compared to values registered at T0 and/or to the values 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 | Analysis of modification of the serological inflammatory biomarkers evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum: interleukin (IL)-8 | Expression of serological inflammatory biomarkers will be evaluated, on all the samples collected, by multiplexing simultaneous analysis with high sensitivity microsphere-based assays or ELISA.
interleukin (IL)-8 values difference will be considered relevant for p<0.05 compared to values registered at T0 and/or to the values 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 | Analysis of modification of the serological inflammatory biomarkers evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum: interleukin (IL)-9 | Expression of serological inflammatory biomarkers will be evaluated, on all the samples collected, by multiplexing simultaneous analysis with high sensitivity microsphere-based assays or ELISA.
interleukin (IL)-9 values difference will be considered relevant for p<0.05 compared to values registered at T0 and/or to the values 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 | Analysis of modification of the serological inflammatory biomarkers evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum: interleukin (IL)-10 | Expression of serological inflammatory biomarkers will be evaluated, on all the samples collected, by multiplexing simultaneous analysis with high sensitivity microsphere-based assays or ELISA.
interleukin (IL)-10 values difference will be considered relevant for p<0.05 compared to values registered at T0 and/or to the values 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 | Analysis of modification of the serological inflammatory biomarkers evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum: interleukin (IL)-12 | Expression of serological inflammatory biomarkers will be evaluated, on all the samples collected, by multiplexing simultaneous analysis with high sensitivity microsphere-based assays or ELISA.
interleukin (IL)-12 values difference will be considered relevant for p<0.05 compared to values registered at T0 and/or to the values 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 | Analysis of modification of the serological inflammatory biomarkers evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum: interleukin (IL)-13 | Expression of serological inflammatory biomarkers will be evaluated, on all the samples collected, by multiplexing simultaneous analysis with high sensitivity microsphere-based assays or ELISA.
interleukin (IL)-13 values difference will be considered relevant for p<0.05 compared to values registered at T0 and/or to the values 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 | Analysis of modification of the serological inflammatory biomarkers evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum: interleukin (IL)-15 | Expression of serological inflammatory biomarkers will be evaluated, on all the samples collected, by multiplexing simultaneous analysis with high sensitivity microsphere-based assays or ELISA.
interleukin (IL)-15 values difference will be considered relevant for p<0.05 compared to values registered at T0 and/or to the values 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 | Analysis of modification of the serological inflammatory biomarkers evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum: interleukin (IL)-17 | Expression of serological inflammatory biomarkers will be evaluated, on all the samples collected, by multiplexing simultaneous analysis with high sensitivity microsphere-based assays or ELISA.
interleukin (IL)-17 values difference will be considered relevant for p<0.05 compared to values registered at T0 and/or to the values 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 | Analysis of modification of the serological inflammatory biomarkers evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum: interleukin (IL)-21 | Expression of serological inflammatory biomarkers will be evaluated, on all the samples collected, by multiplexing simultaneous analysis with high sensitivity microsphere-based assays or ELISA.
interleukin (IL)-21 values difference will be considered relevant for p<0.05 compared to values registered at T0 and/or to the values 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 | Analysis of modification of the serological inflammatory biomarkers evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum: interleukin (IL)-22 | Expression of serological inflammatory biomarkers will be evaluated, on all the samples collected, by multiplexing simultaneous analysis with high sensitivity microsphere-based assays or ELISA.
interleukin (IL)-22 values difference will be considered relevant for p<0.05 compared to values registered at T0 and/or to the values 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 | Analysis of modification of the serological inflammatory biomarkers evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum: interleukin (IL)-33 | Expression of serological inflammatory biomarkers will be evaluated, on all the samples collected, by multiplexing simultaneous analysis with high sensitivity microsphere-based assays or ELISA.
interleukin (IL)-33 values difference will be considered relevant for p<0.05 compared to values registered at T0 and/or to the values 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 | Analysis of modification of the serological inflammatory biomarkers evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum: tumor necrosis factor (TNF)-a | Expression of serological inflammatory biomarkers will be evaluated, on all the samples collected, by multiplexing simultaneous analysis with high sensitivity microsphere-based assays or ELISA.
Tumor necrosis factor (TNF)-a values difference will be considered relevant for p<0.05 compared to values registered at T0 and/or to the values 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 | Analysis of immunophenotyping of whole blood for quantification of immune cell (IC) subpopulations modification and their activation status evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum | Immunophenotyping will be performed by multi-color flow cytometry. Blood will be stained with fluorochrome conjugated antibodies specific for surface markers of cell population lineages and immune activation to allow the quantification of immune cell populations and their activation status Immune cell populations difference will be considered relevant for p<0.05 compared to values registered at T0 and/or to the values 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 | Identification of T cell lymphocytes able to recognize cognate peptides from wheat proteins | To identify T cells able to recognize cognate peptides from wheat proteins, CD45+ immune cells will be collected from rectal biopsy specimens obtained from 10 patients, at baseline and when they will report symptom's recurrence on double-blind wheat challenge. Rectal biopsies will be transferred in complete culture medium, minced into small pieces, followed by enzymatic digestion. Then CD45+ fraction will be sorted and used for subsequent -omic analyses. Immune cells obtained from the biopsies will undergo Single Cell characterization, aiming to investigate changes in the immune microenvironment, by CITE-seq and TCR-seq analyses. To gain insight into T Cell Receptor sequences able to recognize putative peptides originated from the main wheat proteins (gluten, etc.), we will develop a neural network/docking predictive model for TCR/epitope interaction. The final wheat peptides candidates will be then validated in vitro by using an Elispot assay. | 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 | Analysis of gut microbiota modification evoked by dietary exposition to Triticum Monococcum and Triticum Aestivum | in vitro identification of gut microbiota will be performed by amplification, analysis and quantification of gut microbiome on stools samples. After fecal collection, bacterial DNA will be extracted by cetyltrimethyl ammonium bromide, and 16S rDNA sequencing will be performed by polymerase chain reaction (PCR) methods, using universal primers. The resulting fragments will be then sequenced by pyrosequencing. Each reading will be compared with a database of known 16S rDNA sequences, using the BLAT program by phylogenetically assigning the most specific and reliable nodes. This method of assigning the obtained data leads to a "weighted" phylogenetic tree that characterizes well the bacterial content of the sample.
Gut microbiota difference will be considered relevant for p<0.05 compared to values registered at T0 and/or to the values 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) |
Status | Clinical Trial | Phase | |
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Recruiting |
NCT05555446 -
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