Bioelectrical Impedance Analysis of Not-celiac Wheat Sensitivity Patients
Condition: Not-celiac Gluten (Wheat) Sensitivity
MeSH terms: Celiac Disease; Hypersensitivity
Study type: Interventional

Summary: 
      Aim of the investigators' study is to evaluate one of the symptoms described by patients
      affected with the so-called "not-celiac wheat sensitivity" (NCWS). NCWS patients may be
      defined as ones, neither celiac or allergic to wheat, who develop symptoms following wheat
      consumption and improve on Gluten Free Diet (GFD). Among these, patients often report the
      appearance of bloating and abdominal pain, and, sometimes, swelling of fingers and face,
      shortly after ingestion of wheat. They also refer that swelling tends to last for some hours
      and then to disappear on GFD. To our knowledge, this disorder has never been investigated
      neither proved.

      For the investigators' research, the investigators selected adult patients, both genders,
      affected with NCWS. Diagnostic criteria include: 1) symptoms disappearance on GFD, 2) testing
      negative for celiac disease [anti-tTG and EMA, and with biopsy Marsh 0-1] and wheat allergy
      [serum specific IgE for wheat], 3) positive response to a double-blind placebo-controlled
      challenge (DBPC) with wheat or placebo.

      Patients will be recruited among subjects referring, as outpatients, to 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. The investigators
      will include patients referring for functional dyspepsia and/or irritable bowel syndrome
      (IBS)-like symptoms. All recruited patients must report body's swelling immediately after
      wheat ingestion. In all recruited patients, NCWS diagnosis was posed during the previous
      years, according to the above mentioned criteria.

      Patients, all on GFD for at least 30 days, will undergo to another DBPC with wheat or placebo
      (xylose), performed by administering capsules coded as A or B containing wheat or xylose,
      respectively. Capsules A or B will be administered once, and then, after 1 week of washout,
      patients received the other capsules, given once too. Before and 2 hours after every
      challenge, patients will undergo a complete medical examination (measurement of body weight,
      height, body mass index [BMI], waist circumference, diameter of thighs, legs, arms, and
      fingers), and we will perform bioelectrical impedance analysis and collect blood sampling,
      for identification of possible markers (bioelectrical, immunologic, hormonal, etc) that may
      help to demonstrate and explain mechanisms of examined symptom.
    

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, that, combined, seems to
      affect about 10% of the general population. The frequency of not-celiac gluten sensitivity 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 immunoglobulin E (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 gluten sensitivity. Some subjects, who experience symptoms
      when eating gluten-containing products and show improvement when following a gluten-free
      diet, may have gluten sensitivity instead of celiac disease or wheat allergy. Gluten
      sensitivity 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 gluten sensitivity 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-tissue
      transglutaminase, tTG, or anti-endomysium, 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.

      As it is not known what cereals components determine the symptoms in the so called gluten
      sensitivity patients, we prefer to define this condition as "wheat sensitivity" instead of
      "gluten sensitivity".

      Wheat sensitivity can cause both gastrointestinal and extra-intestinal symptoms; among the
      latter, the patients often reported body's swelling (hands', fingers', arms' , face's
      swelling).

      This study has two major aims:

        1. Evaluation of the effective dependence from the wheat ingestion of the clinical
           alterations presented by patients with diagnosed gluten sensitivity, with particular
           attention to abdominal bloating and body's swelling. The study will be done after a
           period of gluten-free diet (at least 30 days), using a double-blind placebo-controlled
           challenge with wheat or placebo (xylose), performed by administering capsules coded as A
           or B containing wheat or xylose, respectively. Capsules A or B will be administered
           once, and then, after 1 week of washout, the patients received the other capsules, given
           once too.

        2. Before and 2 hours after every challenge, patients will undergo a complete medical
           examination, and The investigators will perform bioelectrical impedance analysis and
           collect blood sampling, for identification of possible markers that may be of help to
           demonstrate and explain the mechanisms of the examined symptom.
    

Intervention name(s): wheat; xylose
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): wheat is administered blindly versus placebo in capsules once; placebo (xylose) will be administered blindly versus wheat in a capsule once
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Diagnostic
Keywords: Not-celiac gluten (wheat) sensitivity; Bioelectrical impedance analysis; Bloating; Swelling