Response to Different Wheat Genotypes in Not-celiac Wheat Sensitivity

Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-65
SponsorUniversity of Palermo

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

age <18 years

positive EmA in the culture medium of the duodenal biopsies, even if the villi to crypts ratio in the duodenal mucosa was normal

self-exclusion of wheat from the diet and refusal to reintroduce it before entering the study

other organic gastrointestinal diseases (i.e. careful exclusion of Crohn's disease)

Trial design

Design model

Crossover

Treatments tested in this trial

  • Wheat flour

    Dietary supplement

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

  • Placebo

    Dietary supplement

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

Treatment groups

50 Participants
are divided into 4 treatment groups
Group A: Active Comparator 1Active comparator 1 intervention
Group B: Active Comparator 2Active comparator 1 intervention
Group C: Placebo 1Placebo comparator 1 intervention
Group D: Placebo 2Placebo comparator 1 intervention

Trial outcomes

Primary outcomes

1

Inflammatory response to wheat genotypes by PBMC of NCWS patients and healthy control subjects.

Cytokines 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.

Time frame
Through study completion, an average of 6 months
2

Inflammatory response to wheat genotypes by rectal immunocytes of NCWS patients and healthy control subjects.

Rectal 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.

Time frame
Through study completion, an average of 6 months

Secondary outcomes

1

Clinical response to wheat genotypes in NCWS patients

Symptoms 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.

Time frame
Change from baseline at 2 weeks

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.