Bio-markers of Not-celiac Wheat Sensitivity

June 17, 2025 updated by: Pasquale Mansueto, University of Palermo

Not-celiac Wheat Sensitivity (NCWS) in Patients With Irritable Bowel Syndrome. Randomized Double-Blind Placebo-Controlled Trial (Wheat vs Placebo) for Bio-markers Identification of NCWS and Understanding Its Pathogenetic Mechanisms.

The aim of the investigators' study is to evaluate biochemical, immunological and histological characteristics of patients affected with the so-called "gluten (or wheat) sensitivity" who suffers from irritable bowel syndrome (IBS)-like symptoms.

As it is not known what component of the cereals causes the symptoms in so called "gluten-sensitive" patients, the investigators prefer to speak of "not-celiac wheat sensitivity" (NCWS).

NCWS patients may be defined as ones, neither celiac or allergic to wheat, who develop symptoms following wheat consumption, that improved on wheat/gluten free diet (GFD). For our research, we will select adult patients, both genders, affected with suspected NCWS (i.e. with symptoms/signs which disappeared on GFD and worsen on a gluten containing diet, testing negative for celiac disease [anti-tissue transglutaminase antibodies, anti-tTG, and anti-endomysium antibodies, EMA, and with biopsy Marsh 0-1] and wheat allergy [serum specific IgE for wheat]). The patients will be recruited at the Department of Internal Medicine, 'Giovanni Paolo II' Hospital of Sciacca (Agrigento), and of Internal Medicine of the University of Palermo, from January 2012 to October 2013, for IBS-like symptoms.

At the time of the recruitment, the patients will be on GFD by at least one month and must be asymptomatic. A more restricted elimination diet (with the exclusion of cow's milk, egg and other foods) could be prescribed in patients who are suspected to suffer from multiple food hypersensitivity. The patients will be randomized to undergo a double-blind placebo-controlled study, assuming wheat flour or placebo, administered daily for 15 days. Before and after the challenge, the investigators will evaluate gastrointestinal (Gastrointestinal Symptom Rating Scale, GSRS) and the investigators will collect blood and fecal sampling and biopsies from endoscopic evaluation (both esophagogastroduodenoscopy and rectoscopy, with multiple biopsies), for the identification of possible markers (serological, biochemical, immunological, histological features, expression of cytokines and other constitutive mucosal proteins from peripheral blood mononuclear cells, mucosal lymphocytes and fecal biomarkers) that may be of help to diagnose the condition of NCWS and to understand its pathogenesis.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Gluten is the most important protein component of some grains, notably wheat, rye, and barley, which are the basis for a variety of wheat-derived alimentary products consumed throughout the world (bread, pasta, pizza etc). However the "engineering" of gluten-containing grains created the conditions for human diseases related to gluten exposure. These forms of gluten intolerance represent a heterogeneous set of conditions, including celiac disease, wheat allergy and gluten sensitivity (GS), that, combined, seems to affect about 10% of the general population. The frequency of not-celiac GS is however still unknown, even though it is possible that this condition have been undiagnosed and under-diagnosed by the physicians for a long time. The immune responsiveness to wheat antigens represents a complex process, and its establishment and maintenance are not completely elucidated. The most frequent diseases caused by wheat ingestion are T cell-mediated disorders, i.e. celiac disease and IgE-mediated allergic reactions. However, besides celiac disease and wheat allergy, there are cases of gluten reactions in which neither autoimmune nor IgE-mediated allergic mechanisms are involved. These are generally defined as GS. Some subjects, who experience symptoms when eating gluten-containing products and show improvement when following a gluten-free diet (GFD), may have GS instead of celiac disease or wheat allergy. GS patients are unable to tolerate gluten and develop an adverse reaction when eating gluten, that, usually, and differently from celiac disease, does not lead to small intestinal damage. Gastrointestinal symptoms in GS patients may resemble those associated with celiac disease, but the overall clinical picture is generally less severe and is not accompanied by the occurrence of autoantibodies (i.e. anti-tTG or EMA) or autoimmune disease (i.e. Hashimoto's thyroiditis). Typically, the diagnosis is made by exclusion, and an elimination diet and an "open challenge" (i.e., the monitored reintroduction of gluten-containing foods) are most often used to evaluate whether health improves or worsen with the elimination or reintroduction of gluten in the diet, respectively. Gluten-sensitivity can cause both gastrointestinal and extra-intestinal symptoms; among the former, the most frequent are IBS-like symptoms including abdominal pain, bloating, diarrhea, constipation and alternate bowel habit. However, as it is not known what component of the cereals causes the symptoms in so called "gluten-sensitive" patients, we prefer to speak of "Not-celiac wheat sensitivity" (NCWS). Furthermore, in our experience, NCWS patients can suffer from multiple food hypersensitivity and need of a more restricted diet with the elimination of cow's milk, egg and other foods, in addition to wheat. For these reasons, before to undergo the gluten challenge, the patients will undergo an oligoantigenic diet.

This study has two major aims:

  1. Evaluation of the effective dependence from the wheat of the IBS-like manifestations presented by subjects with suspected NCWS. The study will be done after a period of GFD, comparing two groups of suspected NCWS subjects: administering wheat flour or placebo (for 15 days).
  2. Identification of possible markers (serological, biochemical, immunological, histological features, expression of cytokines and other constitutive mucosal proteins from peripheral blood mononuclear cells, mucosal lymphocytes and fecal biomarkers) that may be of help to diagnose the condition of NCWS. In particular, the investigators will search for markers of NCWS in the colon mucosa of the patients with IBS-like symptoms.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
100

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

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, 90100
        • Recruiting
        • Internal Medicine, University Hospital
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Alberto D'Alcamo, MD
        • Sub-Investigator:
          • Giusi Randazzo, MD
        • Sub-Investigator:
          • Miriam Carta, MD
        • Sub-Investigator:
          • Giuseppe Taormina, MD
    • Agrigento
      • Sciacca, Agrigento, Italy
        • Recruiting
        • Internal Medicine, "Giovanni Paolo II" Hospital
        • Contact:
        • Contact:

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Adult patients, both genders, with age between 18-65 years, with IBS-like symptoms, that improved on a gluten free diet and worsen on a gluten containing diet
  • Patients testing negative for celiac disease ( anti-tTG and EMA negative, and with biopsy Marsh 0-1) and wheat allergy (serum specific igE for wheat negative)

Exclusion Criteria:

  • Subjects diagnosed with celiac disease (positive anti-tTG and/or EMA, and positive histology, with Marsh 2 or above);
  • Subjects diagnosed with wheat allergy (positive serum specific IgE for wheat)
  • Subjects with Type 1 Diabetes
  • Subjects with Inflammatory Bowel Diseases (Crohn's disease or ulcerative colitis)
  • Subjects with Helicobacter pylori infection and other gastrointestinal infection
  • Pregnancy

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

  • Primary Purpose: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: wheat flour
wheat flour is administered blindly versus placebo for 15 days
Dietary supplement: wheat flour
wheat flour is administered three times per day for 15 days
Dietary supplement: Xylose
Xylose will be administered three times per day for 15 days
Placebo Comparator: Xylose
placebo will be administered blindly versus wheat flour for 15 days
Dietary supplement: wheat flour
wheat flour is administered three times per day for 15 days
Dietary supplement: Xylose
Xylose will be administered three times per day for 15 days

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Symptoms/signs evaluation
Time Frame: Change from baseline (i.e. before diagnosis of suspected NCWS, on free diet, and after diagnosis of suspected NCWS, on GFD) at 2 weeks
Symptoms/signs evaluation, before and after the challenge: total score before and after 2 weeks of wheat (or placebo) ingestion
Change from baseline (i.e. before diagnosis of suspected NCWS, on free diet, and after diagnosis of suspected NCWS, on GFD) at 2 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Bio-Markers evaluation
Time Frame: Change from baseline (i.e. before diagnosis of suspected NCWS, on free diet, and after diagnosis of suspected NCWS, on GFD) at 2 weeks
Bio-Markers to diagnose GS and understand its pathogenesis
Change from baseline (i.e. before diagnosis of suspected NCWS, on free diet, and after diagnosis of suspected NCWS, on GFD) at 2 weeks

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Palermo

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Antonio Carroccio, PHD, MD, Internal Medicine, 'Giovanni Paolo II' Hospital of Sciacca (Agrigento) and University of Palermo, Palermo, Italy

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2012

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2016

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 4, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 4, 2013

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 7, 2013

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 22, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 17, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ACPM03

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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.

Clinical Trials on Not-celiac Wheat Sensitivity

Clinical Trials on wheat flour

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings