Bio-markers of Not-celiac Wheat Sensitivity

This study is currently recruiting participants.
Verified January 2013 by University of Palermo
Sponsor:
Information provided by (Responsible Party):
Pasquale Mansueto, University of Palermo
ClinicalTrials.gov Identifier:
NCT01762579
First received: January 4, 2013
Last updated: January 7, 2013
Last verified: January 2013
  Purpose

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 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 and mucosal lymphocytes) that may be of help to diagnose the condition of NCWS and to understand its pathogenesis.


Condition Intervention Phase
Not-celiac Wheat Sensitivity
Dietary Supplement: wheat flour
Dietary Supplement: Xylose
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Diagnostic
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by University of Palermo:

Primary Outcome Measures:
  • Symptoms/signs evaluation [ Time Frame: Change from baseline at 2 weeks ] [ Designated as safety issue: Yes ]
    Symptoms/signs evaluation, before and after the challenge: total score before and after 2 weeks of wheat (or placebo) ingestion


Secondary Outcome Measures:
  • Bio-Markers evaluation [ Time Frame: Change from baseline at 2 weeks ] [ Designated as safety issue: Yes ]
    Bio-Markers to diagnose GS and understand its pathogenesis


Estimated Enrollment: 40
Study Start Date: January 2012
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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 GS. 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 and mucosal lymphocytes) 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.
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01762579

Locations
Italy
Internal Medicine, "Giovanni Paolo II" Hospital Recruiting
Sciacca, Agrigento, Italy
Contact: Antonio Carroccio, PHD    +39-091-6554335    acarroccio@hotmail.com   
Contact: Pasquale Mansueto, MD    +39-091-6554335    pasquale.mansueto@unipa.it   
Internal Medicine, University Hospital Recruiting
Palermo, Italy, 90100
Contact: Antonio Carroccio, PHD    +39-091-6554335    acarroccio@hotmail.com   
Contact: Pasquale Mansueto, MD    +39-091-6554335    pasquale.mansueto@unipa.it   
Sub-Investigator: Alberto D'Alcamo, MD         
Sub-Investigator: Giusi Randazzo, MD         
Sub-Investigator: Miriam Carta, MD         
Sub-Investigator: Giuseppe Taormina, MD         
Sponsors and Collaborators
University of Palermo
Investigators
Principal Investigator: Antonio Carroccio, PHD, MD Internal Medicine, 'Giovanni Paolo II' Hospital of Sciacca (Agrigento) and University of Palermo, Palermo, Italy
  More Information

No publications provided

Responsible Party: Pasquale Mansueto, MD, University of Palermo
ClinicalTrials.gov Identifier: NCT01762579     History of Changes
Other Study ID Numbers: ACPM03
Study First Received: January 4, 2013
Last Updated: January 7, 2013
Health Authority: Italy: Ministry of Health

Keywords provided by University of Palermo:
Not-celiac wheat sensitivity
Gluten
esophagogastroduodenoscopy
Rectoscopy

Additional relevant MeSH terms:
Celiac Disease
Irritable Bowel Syndrome
Malabsorption Syndromes
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Metabolic Diseases
Colonic Diseases, Functional
Colonic Diseases

ClinicalTrials.gov processed this record on April 16, 2014