Gluten Sensitivity in Non-Celiac Patients
Condition: Gluten Sensitivity
MeSH terms: Hypersensitivity
Study type: Interventional
Phase: Phase 3

Summary: 
      The idea is to evaluate if the so called "Gluten Sensitivity" is a real clinical entity.
      Gluten sensitive (GS) persons are defined as those patients, being neither celiac or allergic
      to weat, who develop symptoms following gluten consumption. This will be achieved by
      evaluating a global symptom score in GS patients receiving gluten compared to those receiving
      placebo (primary end point). Symptoms to be evaluated: gastrointestinal (Gastrointestinal
      Symptom Rating Scale, GSRS); not-gastrointestinal (specifically built evaluation scale); VQV
      scale, built to evaluate quality of life. Gluten or placebo will be administered daily (10 g)
      for 15 days; for the 15 days before and 15 after all patients will stay on Gluten Free Diet
      (GFD). Besides clinical evaluation (each week for 6 weeks), intestinal permeability testing
      and blood sampling will be requested for the identification of possible markers (serological,
      gut barrier function, immunological and expression of tight junctions constitutive proteins)
      that may be of help to differentiate the condition of gluten sensitivity (GS) from that of
      Celiac Disease (CD)(secondary end point). Inclusion and exclusion criteria for patients
      enrolling are strictly dependant on the given "Gluten sensitivity" definition. We expect to
      experience a worsening of gastrointestinal and extra-gastrointestinal symptoms, from hours to
      days, with an increase in the overall symptom score, above the cut off, in at least 45% of GS
      subjects enrolled and that have received gluten compared to GS who received placebo.
    

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 flour and 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 wheat allergy, Gluten Sensitivity and Celiac Disease, that, combined, affect about
      10% of the general population. The frequency of not-celiac gluten intolerance is however
      still unknown, even though it is possible that these conditions have been undiagnosed and
      under-diagnosed by the physicians for long time. The state of 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, IgE-mediated allergic reactions and celiac disease (CD).

      However, besides CD and wheat allergy, there are cases of gluten reactions in which neither
      allergic nor autoimmune mechanisms are involved. These are generally defined as gluten
      sensitivity (GS). Some individuals, who experience distress when eating gluten-containing
      products and show improvement when following a gluten-free diet, may have GS instead of CD.
      GS patients are unable to tolerate gluten and develop an adverse reaction when eating gluten
      that usually, and differently from CD, does not lead to small intestinal damage. While the
      gastrointestinal symptoms in GS may resemble those associated with CD, the overall clinical
      picture is generally less severe and is not accompanied by the concurrence of tTG
      autoantibodies or autoimmune disease. Typically the diagnosis is made by exclusion, and an
      elimination diet and "open challenge" (i.e., the monitored reintroduction of
      gluten-containing foods) are most often used to evaluate whether health improves with the
      elimination or reduction of gluten from the diet.

      This has two major aims:

        1. Evaluation of the effective dependence from the gluten of the clinical alterations
           presented by subjects with gluten sensitivity (GS). The study will be done after a
           period of gluten-free diet (washout of 15 days), comparing two groups of GS subjects:
           given gluten or placebo (15 days), followed by a further period (15 days) on gluten free
           diet .

        2. identification of possible markers (serological, gut barrier function, immunological and
           expression of tight junctions constitutive proteins) that may be of help to
           differentiate, in humans, the condition of gluten sensitivity (GS) from that of Celiac
           Disease (CD); these markers might be of help in the early diagnosis of GS versus CD
           especially in the case of discordant serology.
    

Intervention name(s): gluten; rice starch
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): gluten is administered once a day at 10g/day for 15 days; rice starch is administered once a day at 10 g/day for 15 days
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Diagnostic
Keywords: gluten sensitivity