Response to Different Wheat Genotypes in Not-celiac Wheat Sensitivity

Study Purpose

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.#46; modern), or the technological properties (cultivars with weak glutens vs.#46; 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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years - 65 Years
Gender All
More Inclusion & Exclusion Criteria

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.

Exclusion Criteria:

Exclusion criteria will be:
  • - 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) - concomitant treatment with steroids and/or antihistamines.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03024775
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

N/A
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

University of Palermo
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Antonio Carroccio, PhD
Principal Investigator Affiliation University of Palermo
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Recruiting
Countries Italy
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Non-celiac Wheat Sensitivity
Additional Details

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.#46; modern), or the technological properties (cultivars with weak glutens vs.#46; 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.

Arms & Interventions

Arms

Active Comparator: Active Comparator 1

Wheat flour with high inflammatory response will be administered blindly versus placebo for 15 days in NCWS patients.

Active Comparator: Active Comparator 2

Wheat flour with low inflammatory response will be administered blindly versus placebo for 15 days in NCWS patients.

Placebo Comparator: Placebo 1

Placebo (xylose) will be administered blindly versus wheat flour with high inflammatory response for 15 days in NCWS patients.

Placebo Comparator: Placebo 2

Placebo (xylose) will be administered blindly versus wheat flour with low inflammatory response for 15 days in NCWS patients.

Interventions

Dietary Supplement: - Wheat flour

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

Dietary Supplement: - Placebo

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

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Sciacca, Agrigento, Italy

Status

Recruiting

Address

Department of Internal Medicine, Giovanni Paolo II Hospital of Sciacca

Sciacca, Agrigento, 92019

Site Contact

Antonio Carroccio, MD, PhD

acarroccio@hotmail.com

+390916554347

Palermo, Italy

Status

Recruiting

Address

Department of Internal Medicine, University Hospital of Palermo

Palermo, , 90129

Site Contact

Pasquale Mansueto, MD

pasquale.mansueto@unipa.it

+390916554347

The content provided by the Celiac Disease Foundation on clinical trials is for informational purposes only and is not a substitute for medical consultation with your healthcare provider. We do not recommend or endorse any specific study and you are advised to discuss the information shown with your healthcare provider. While we believe the information presented on this website to be accurate at the time of writing, we do not guarantee that its contents are correct, complete, or applicable to any particular individual situation. We strongly encourage individuals to seek out appropriate medical advice and treatment from their physicians. We cannot guarantee the availability of any clinical trial listed and will not be responsible if you are considered ineligible to participate in a given clinical trial. We are also not liable for any injury arising as a result of participation. For a full description of terms please refer to: Privacy Policy and Terms of Use.