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

July 9, 2017 updated by: Pasquale Mansueto, University of Palermo
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Observational

Enrollment (Actual)

80

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Palermo, Italy, 90129
        • Department of Internal Medicine, University Hospital of Palermo
    • Agrigento
      • Sciacca, Agrigento, Italy, 92019
        • Department of Internal Medicine, Giovanni Paolo II Hospital of Sciacca

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 63 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

The study will include consecutive adult patients with IBS-like clinical presentation, according to Rome III criteria, and a definitive diagnosis of NCWS, referred at the Department of Internal Medicine at the University Hospital of Palermo, Italy, and at the Department of Internal Medicine of the Hospital of Sciacca, Agrigento, Italy, between July 2016 to February 2017, and sex- and age-matched subjects with IBS, enrolled at the same centers, as controls patients. All subjects will undergo upper gastrointestinal endoscopy and proctoscopy at the Gastroenterology Unit at the University Hospital of Palermo. Duodenal and rectal biopsies will be evaluated at 2 centers: the Pathology Unit at the University Hospital of Palermo, Italy, and the Institute of Pathology, Spedali Civili Brescia, Brescia, Italy.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
NCWS patients
Forty consecutive adult patients with an IBS-like clinical presentation, according to Rome III criteria, and a definitive diagnosis of NCWS. The patients will be recruited between January 2016 and February 2017 at 2 centers: the Department of Internal Medicine at the University Hospital of Palermo, Italy, and the Department of Internal Medicine of the Hospital of Sciacca, Agrigento, Italy. All subjects will undergo upper gastrointestinal endoscopy and proctoscopy at the Gastroenterology Unit at the University Hospital of Palermo, Italy. Duodenal and rectal biopsies will be evaluated at 2 centers: the Pathology Unit at the University Hospital of Palermo, Italy, and the Institute of Pathology at the "Spedali Civili" of Brescia, Italy.
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.
IBS patients
Forty sex- and age-matched subjects with IBS unrelated to NCWS or other food 'intolerance', diagnosed according to standard criteria during the same study period and enrolled, at the same 2 centers, as control group. All subjects will undergo upper gastrointestinal endoscopy and proctoscopy at the Gastroenterology Unit at the University Hospital of Palermo, Italy. Duodenal and rectal biopsies will be evaluated at 2 centers: the Pathology Unit at the University Hospital of Palermo, Italy, and the Institute of Pathology at the "Spedali Civili" of Brescia, Italy.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Histological differences in duodenal biopsies between NCWS and IBS patients.
Time Frame: July 2016 to February 2017
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
Histological differences in rectal biopsies between NCWS and IBS patients.
Time Frame: July 2016 to February 2017
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Identification of site (i.e. duodenal or rectal) with more inflammatory cells infiltration.
Time Frame: July 2016 to February 2017
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Palermo

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2016

Primary Completion (Actual)

January 1, 2017

Study Completion (Actual)

July 1, 2017

Study Registration Dates

First Submitted

December 30, 2016

First Submitted That Met QC Criteria

January 12, 2017

First Posted (Estimate)

January 18, 2017

Study Record Updates

Last Update Posted (Actual)

July 12, 2017

Last Update Submitted That Met QC Criteria

July 9, 2017

Last Verified

July 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACPM18

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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