Duodenal and Rectal Histology in Non-celiac Wheat Sensitivity and Irritable Bowel Syndrome Patients

Non-celiac Wheat Sensitivity Clinical Trial

Official title:

Duodenal and Rectal Histology in Non-celiac Wheat Sensitivity and Irritable Bowel Syndrome Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03022994
• Other study ID #: ACPM18
• Status: Completed
• Phase: N/A
• First received: December 30, 2016
• Last updated: July 9, 2017
• Start date: January 2016
• Est. completion date: July 2017

Study information

• Verified date: July 2017
• Source: University of Palermo
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Recently it has been reported that a consistent percentage of the general population consider themselves to be suffering from problems caused by wheat and/or gluten ingestion, even though they do not have CD or wheat allergy. This clinical condition has been named Non-Celiac Gluten Sensitivity' (NCGS). In a previous paper the investigators suggested the term 'Non-Celiac Wheat Sensitivity' (NCWS), since it is not known what component of wheat causes the symptoms in NCGS patients, and the investigators also showed that these patients had a high frequency of coexistent multiple food hypersensitivity. Nowadays only few data are available on the histological characteristic of duodenal and rectal biopsies of NCWS patients. The researchers have just demonstrated a significant eosinophils infiltration of the duodenal and colon mucosa, and a significant infiltration of CD45+/CD3-CD14- cells in the rectal mucosa of NCWS patients upon wheat challenge, thus configuring a diffuse gastrointestinal "inflammatory/immunologic" pattern. The aims of the present study are: 1) to investigate the histological characteristics in duodenal and rectal biopsies between NCWS and irritable bowel syndrome (IBS) patients, and 2) to evaluate which site (i.e. duodenal or rectal) shows "inflammatory/allergic" features useful for NCWS histological diagnosis.

Description:

Recently it has been reported that a consistent percentage of the general population consider themselves to be suffering from problems caused by wheat and/or gluten ingestion, even though they do not have CD or wheat allergy. This clinical condition has been named Non-Celiac Gluten Sensitivity' (NCGS). In a previous paper the investigators suggested the term 'Non-Celiac Wheat Sensitivity' (NCWS), since it is not known what component of wheat causes the symptoms in NCGS patients, and the investigators also showed that these patients had a high frequency of coexistent multiple food hypersensitivity. The clinical picture of NCWS is characterized by combined gastrointestinal (bloating, abdominal pain, diarrhea and/or constipation, nausea, epigastric pain, gastroesophageal reflux, aphthous stomatitis) and extra-intestinal and/or systemic manifestations (headache, depression, anxiety, 'foggy mind,' tiredness, dermatitis or skin rash, fibromyalgia-like joint/muscle pain, leg or arm numbness, and anemia). Nowadays only few data are available on the histological characteristic of duodenal and rectal biopsies of NCWS patients. The researchers have just demonstrated a significant eosinophils infiltration of the duodenal and colon mucosa, and a significant infiltration of CD45+/CD3-CD14- cells in the rectal mucosa of NCWS patients upon wheat challenge, thus configuring a diffuse gastrointestinal "inflammatory/immunologic" pattern. As regard to rectal lymphocytes, analysis of cytokine production demonstrated dominant spontaneous interferon (IFN)-γ production by these cells, which were further identified as innate lymphoid cells belonging to the group 1 (ILC1) population, expressing T-bet and producing IFN-γ, compatible to an innate immunity involvement in NCWS pathogenesis. Therefore, the aims of the present study are: 1) to investigate the histological characteristics and differences in duodenal and rectal biopsies between NCWS and IBS patients, and 2) to search for "inflammatory/allergic" features (i.e. eosinophils and/or lymphocytes infiltration) useful for NCWS histological diagnosis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: July 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

To diagnose NCWS the recently proposed criteria will be adopted. All the patients will meet the following criteria:

• negative serum anti-transglutaminase (anti-tTG) and anti-endomysium (EmA) immunoglobulin (Ig)A and IgG antibodies

• absence of intestinal villous atrophy

• negative IgE-mediated immune-allergy tests to wheat (skin prick tests and/or serum specific IgE detection)

• resolution of the IBS symptoms on standard elimination diet, excluding wheat, cow's milk, egg, tomato, chocolate, and other self-reported food(s) causing symptoms

• symptom reappearance on double-blind placebo-controlled (DBPC) wheat challenge. As the investigators previously described in other studies, DBPC cow's milk protein challenge and other "open" food challenges will be performed too.

To diagnose IBS the standard Rome II (for retrospective patients) and Rome III (for prospective patients) Criteria will be adopted. None of these subjects improved on an elimination diet without wheat, cow's milk, egg, tomato, or chocolate.

Exclusion Criteria:

NCWS diagnosis will be excluded by:

• positive EmA in the culture medium of the duodenal biopsies, also in the case of normal villi/crypts ratio in the duodenal mucosa

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

• other previously diagnosed gastrointestinal disorders

• other previously diagnosed gynaecological disorders

• nervous system disease and/or major psychiatric disorder

• physical impairment limiting physical activity.

Related Conditions & MeSH terms

• Hypersensitivity
• Irritable Bowel Syndrome
• Non-celiac Wheat Sensitivity

Intervention

Other:
• Duodenum and rectum examination
All subjects will undergo upper gastrointestinal endoscopy and proctoscopy. In addition, it will be also evaluated duodenal and rectal biopsies.

Locations

Country	Name	City	State
Italy	Department of Internal Medicine, University Hospital of Palermo	Palermo
Italy	Department of Internal Medicine, Giovanni Paolo II Hospital of Sciacca	Sciacca	Agrigento

Sponsors (1)

Lead Sponsor	Collaborator
University of Palermo

Country where clinical trial is conducted

Italy, 

References & Publications (7)

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. — View Citation

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. A — View Citation

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. — View Citation

Carroccio A, Soresi M, D'Alcamo A, Sciumè 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. — View Citation

Di Liberto D, Mansueto P, D'Alcamo A, Lo Pizzo M, Lo Presti E, Geraci G, Fayer F, Guggino G, Iacono G, Dieli F, Carroccio A. Predominance of Type 1 Innate Lymphoid Cells in the Rectal Mucosa of Patients With Non-Celiac Wheat Sensitivity: Reversal After a — View Citation

Mansueto P, Seidita A, D'Alcamo A, Carroccio A. Non-celiac gluten sensitivity: literature review. J Am Coll Nutr. 2014;33(1):39-54. doi: 10.1080/07315724.2014.869996. Review. — View Citation

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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Histological differences in duodenal biopsies between NCWS and IBS patients.	Histological characteristics and differences in duodenal biopsies between NCWS and IBS patients, with particular reference to lymphocytes, plasmacells, eosinophils and mast cells (i.e. number of cells for high power field).	July 2016 to February 2017
Primary	Histological differences in rectal biopsies between NCWS and IBS patients.	Histological characteristics and differences in rectal biopsies between NCWS and IBS patients, with particular reference to lymphocytes, plasmacells, eosinophils and mast cells (i.e. number of cells for high power field).	July 2016 to February 2017
Secondary	Identification of site (i.e. duodenal or rectal) with more inflammatory cells infiltration.	Evaluation of which examined site (i.e. duodenal or rectal) presents more lymphocytes and/or eosinophils infiltration (i.e. number of cells for high power field), for NCWS histological diagnosis.	July 2016 to February 2017