Response to Different Wheat Genotypes in Not-celiac Wheat Sensitivity

NCT03024775 | Recruiting

• 1 other identifier: ACPM16
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

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.

Conditions

Non-celiac Wheat Sensitivity

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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.

  Through study completion, an average of 6 months

• 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.

  Through study completion, an average of 6 months

Secondary Outcomes (1)

• Clinical response to wheat genotypes in NCWS patients

  Change from baseline at 2 weeks

Study Arms (4)

Active Comparator 1

ACTIVE COMPARATOR

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

Dietary Supplement: Wheat flour

Active Comparator 2

ACTIVE COMPARATOR

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

Dietary Supplement: Wheat flour

Placebo 1

PLACEBO COMPARATOR

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

Dietary Supplement: Placebo

Placebo 2

PLACEBO COMPARATOR

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

Dietary Supplement: Placebo

Interventions

Wheat flour DIETARY_SUPPLEMENT

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

Active Comparator 1; Active Comparator 2

Placebo DIETARY_SUPPLEMENT

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

Placebo 1; Placebo 2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• concomitant treatment with steroids and/or antihistamines.

Sponsors & Collaborators

• University of Palermo: lead

Study Sites (2)

Department of Internal Medicine, Giovanni Paolo II Hospital of Sciacca

Sciacca, Agrigento, 92019, Italy

RECRUITING

Department of Internal Medicine, University Hospital of Palermo

Palermo, Palermo, 90129, Italy

RECRUITING

Related Publications (8)

• Carroccio A, Mansueto P, Iacono G, Soresi M, D'Alcamo A, Cavataio F, Brusca I, Florena AM, Ambrosiano G, Seidita A, Pirrone G, Rini GB. Non-celiac wheat sensitivity diagnosed by double-blind placebo-controlled challenge: exploring a new clinical entity. Am J Gastroenterol. 2012 Dec;107(12):1898-906; quiz 1907. doi: 10.1038/ajg.2012.236. Epub 2012 Jul 24.

  PMID: 22825366 BACKGROUND

• Carroccio A, Rini G, Mansueto P. Non-celiac wheat sensitivity is a more appropriate label than non-celiac gluten sensitivity. Gastroenterology. 2014 Jan;146(1):320-1. doi: 10.1053/j.gastro.2013.08.061. Epub 2013 Nov 22. No abstract available.

  PMID: 24275240 BACKGROUND

• Carroccio A, D'Alcamo A, Mansueto P. Nonceliac wheat sensitivity in the context of multiple food hypersensitivity: new data from confocal endomicroscopy. Gastroenterology. 2015 Mar;148(3):666-7. doi: 10.1053/j.gastro.2014.11.047. Epub 2015 Jan 24. No abstract available.

  PMID: 25625764 BACKGROUND

• Carroccio A, Soresi M, D'Alcamo A, Sciume C, Iacono G, Geraci G, Brusca I, Seidita A, Adragna F, Carta M, Mansueto P. Risk of low bone mineral density and low body mass index in patients with non-celiac wheat-sensitivity: a prospective observation study. BMC Med. 2014 Nov 28;12:230. doi: 10.1186/s12916-014-0230-2.

  PMID: 25430806 BACKGROUND

• Mansueto P, Seidita A, D'Alcamo A, Carroccio A. Role of FODMAPs in Patients With Irritable Bowel Syndrome. Nutr Clin Pract. 2015 Oct;30(5):665-82. doi: 10.1177/0884533615569886. Epub 2015 Feb 18.

  PMID: 25694210 BACKGROUND

• Spits H, Cupedo T. Innate lymphoid cells: emerging insights in development, lineage relationships, and function. Annu Rev Immunol. 2012;30:647-75. doi: 10.1146/annurev-immunol-020711-075053. Epub 2012 Jan 6.

  PMID: 22224763 BACKGROUND

• Spits H, Di Santo JP. The expanding family of innate lymphoid cells: regulators and effectors of immunity and tissue remodeling. Nat Immunol. 2011 Jan;12(1):21-7. doi: 10.1038/ni.1962. Epub 2010 Nov 28.

  PMID: 21113163 BACKGROUND

• Veldhoen M, Withers DR. Immunology. Innate lymphoid cell relations. Science. 2010 Oct 29;330(6004):594-5. doi: 10.1126/science.1198298. No abstract available.

  PMID: 21030634 BACKGROUND

MeSH Terms

Interventions

Flour

Intervention Hierarchy (Ancestors)

Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Antonio Carroccio, PhD

  University of Palermo

  STUDY DIRECTOR

Central Study Contacts

Antonio Carroccio, PhD

CONTACT

+390916552884; acarroccio@hotmail.com

Pasquale Mansueto, MD

CONTACT

+390916552884; pasquale.mansueto@unipa.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: December 30, 2016
• First Posted: January 19, 2017
• Study Start: January 1, 2017
• Primary Completion: June 1, 2024
• Study Completion (Estimated): December 1, 2026
• Last Updated: June 22, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2)