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Response to Different Wheat Genotypes in Not-celiac Wheat Sensitivity

Clinical Response and Cytokines Production After Challenge With Different Wheat Genotypes in Patients With Not-celiac Wheat Sensitivity.

Status
Recruiting
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT03024775
Enrollment
50
Registered
2017-01-19
Start date
2017-01-01
Completion date
2026-12-01
Last updated
2025-06-22

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Non-celiac Wheat Sensitivity

Keywords

Non-celiac Wheat Sensitivity, ancient wheats, modern wheats, ATIs

Brief summary

Non-celiac gluten sensitivity (NCGS) is a condition where intestinal and extraintestinal symptoms are triggered by gluten ingestion in the absence of celiac disease and wheat allergy. Despite the great interest in NCGS, much remains unknown about the pathogenesis. Some studies seem to suggest that wheat components other than gluten (i.e. amylase/trypsine inhibitors, ATIs) can cause the symptoms, and therefore the term non-celiac wheat sensitivity (NCWS) has been proposed instead of NCGS. It is believed that this condition is worldwide increasing, due to the evolution of wheat breeding (i.e. consumption of wheats with high gluten content), and that ancient wheats are better tolerated by NCWS patients than the modern ones. Therefore, the aim of the study is to determine whether the common belief regarding the fact that ancient wheats are better tolerated by NCWS patients than the modern ones is confirmed by scientific data, and to identify the wheat kernel components triggering this pathology. The availability of wheat materials with opposite characteristics, such as the period of development (ancient vs. modern), or the technological properties (cultivars with weak glutens vs. strong gluten), or the presence/absence of specific ATIs polypeptides, will allow to define the role played by these factors. Therefore, the study has two objectives: 1) extraction and testing of total kernel proteins, in order to evaluate the inflammatory response to gluten and non-gluten proteins by peripheral blood mononuclear cells (PBMC) and immunocytes extracted by the rectal mucosa of NCWS patients and healthy control subjects, and 2) clinically testing two wheat genotypes, selected on the basis of the previous in vitro studies, showing the highest and the lowest in vitro inflammatory response, in order to verify their effect in triggering NCWS symptoms.

Detailed description

Non-celiac gluten sensitivity (NCGS) is a condition where intestinal and extraintestinal symptoms are triggered by gluten ingestion in the absence of celiac disease and wheat allergy. Despite the great interest in NCGS, much remains unknown about the pathogenesis. Some studies seem to suggest that wheat components other than gluten (i.e. amylase/trypsine inhibitors, ATIs) can cause the symptoms, and therefore the term non-celiac wheat sensitivity (NCWS) has been proposed instead of NCGS. NCWS pathogenesis has been attributed to very different mechanisms: innate or adaptive immunity, incomplete digestion and/or absorption of fermentable oligosaccharides and disaccharides, monosaccharides and polyols, and, finally, psychological effect. In addition, it is believed that this condition is worldwide increasing, due to the evolution of wheat breeding (i.e. consumption of wheats with high gluten content), and that ancient wheats are better tolerated by NCWS patients than the modern ones. Therefore, the aim of the study is to determine whether the common belief regarding the fact that ancient wheats are better tolerated by NCWS patients than the modern ones is confirmed by scientific data, and to identify the wheat kernel components triggering this pathology. The availability of wheat materials with opposite characteristics, such as the period of development (ancient vs. modern), or the technological properties (cultivars with weak glutens vs. strong gluten), or the presence/absence of specific ATIs polypeptides, will allow to define the role played by these factors. The researchers take into consideration different tetraploid wheat genotypes derived from the Italian breeding activity carried out during the 20th century in comparison with landraces, primitive and old wheat cultivars previously cultivated and used mostly in Southern Italy for pasta and bread production, together with an experimental genetically modified (GM) wheat line expressing a lower amount of ATIs. For the purpose of the study, the collection has been subdivided into 5 groups, according to the breeding period. Wheat genotypes will be also evaluated for several parameters: protein content, gluten index, quantitative analysis of ATIs proteins by Mass Spectrometry, etc. The project has two objectives, related to the influence of wheat consumption on health: 1) extraction and testing of total kernel proteins, in order to evaluate the inflammatory response to gluten and non-gluten proteins by peripheral blood mononuclear cells (PBMC) and immunocytes extracted by the rectal mucosa of NCWS patients and healthy control subjects, and 2) clinically testing two wheat genotypes, selected on the basis of the previous in vitro studies, showing the highest and the lowest in vitro inflammatory response, in order to verify their effect in triggering NCWS symptoms.

Interventions

DIETARY_SUPPLEMENTWheat flour

Wheat flour will be administered three times per day for 15 days.

DIETARY_SUPPLEMENTPlacebo

Placebo (xylose) will be administered three times per day for 15 days.

Sponsors

University of Palermo
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No

Inclusion criteria

All the patients will meet the recently proposed criteria: * negative serum anti-tissue transglutaminase and antiendomysium (EmA) immunoglobulin (Ig)A and IgG antibodies * absence of intestinal villous atrophy * IgE-mediated immunoallergic tests negative to wheat (skin prick tests and/or serum specific IgE detection) * follow-up duration \>12 months after the initial diagnosis * at least two outpatient visits during the follow-up period. Adjunctive criteria adopted in our patients will be: * resolution of the gastrointestinal symptoms on a standard elimination diet, without wheat, cow's milk, egg, tomato, chocolate, or other food(s) causing self-reported symptoms * symptom reappearance on DBPC wheat challenge, performed as described previously. As in previous studies, DBPC cow's milk protein challenge and other open food challenges will be also performed.

Design outcomes

Primary

MeasureTime frameDescription
Inflammatory response to wheat genotypes by PBMC of NCWS patients and healthy control subjects.Through study completion, an average of 6 monthsCytokines evaluation in response to gluten and non-gluten proteins from total kernel proteins of different wheat genotypes (i.e. ancient vs. modern vs. genetically modified) by PBMC of patients with a definitive diagnosis of NCWS, at the end of the diagnostic Double-Blind Placebo-Controlled (DBPC) wheat challenge, and of healthy control subjects.
Inflammatory response to wheat genotypes by rectal immunocytes of NCWS patients and healthy control subjects.Through study completion, an average of 6 monthsRectal immunocytes evaluation in response to gluten and non-gluten proteins from total kernel proteins of different wheat genotypes (i.e. ancient vs. modern vs. genetically modified) by immunocytes extracted by the rectal mucosa of patients with a definitive diagnosis of NCWS, at the end of the diagnostic Double-Blind Placebo-Controlled (DBPC) wheat challenge, and of healthy control subjects.

Secondary

MeasureTime frameDescription
Clinical response to wheat genotypes in NCWS patientsChange from baseline at 2 weeksSymptoms evaluation before and after a 2 weeks challenge with two wheat genotypes showing the highest and the lowest in vitro inflammatory response in diagnosed NCWS patients on gluten-free diet. During the challenge periods, the severity of symptoms will be recorded: the patients will complete a 100mm visual analog scale, which assesses the specific symptoms they report. The challenges will be considered positive if the same symptoms which had been initially present will reappear after their disappearance on elimination diet.

Countries

Italy

Contacts

Primary ContactAntonio Carroccio, PhD
acarroccio@hotmail.com+390916552884
Backup ContactPasquale Mansueto, MD
pasquale.mansueto@unipa.it+390916552884

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026