Gluten Sensitivity in Non-Celiac Patients (GS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Second University of Naples
Sponsor:
Information provided by (Responsible Party):
Laura de Magistris, Second University of Naples
ClinicalTrials.gov Identifier:
NCT01485341
First received: November 17, 2011
Last updated: May 14, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Gluten Sensitivity
Dietary Supplement: gluten
Dietary Supplement: rice starch
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: Double Blind Randomized Placebo Controlled Multicenter Trial (Gluten vs Placebo) in Gluten Sensitive Subjects

Resource links provided by NLM:


Further study details as provided by Second University of Naples:

Primary Outcome Measures:
  • Symptoms evaluation according to 3 scales: score after 2 weeks of gluten ingestion [ Time Frame: Change from baseline at 2 weeks ] [ Designated as safety issue: Yes ]
    The evaluation will be made according to the score calculated on the basis of three evaluation scales: "Gastrointestinal Symptom Rating Scale "(GSRS), modified, provides a score ranging MIN=15/MAX=60; Extra-gastrointestinal symptoms evaluation scale, proposed on the basis of the symptoms most frequently observed in GS patients, provides a score ranging MIN=9/MAX=34; VQV scale proposed to evaluate the quality of life, provides a score ranging MIN=16/MAX=64. Total score can be no less than 37 (MIN) and not more than 146 (MAX), with a cut-off of 55.


Secondary Outcome Measures:
  • Bio-Markers to differentiate GS and CD [ Time Frame: Change from baseline at 2 weeks ] [ Designated as safety issue: Yes ]
    The 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 when the serology is discordant.

  • Symptoms evaluation according to 3 scales: scores 2 weeks after completion of intervention [ Time Frame: Return to baseline values at 4 weeks ] [ Designated as safety issue: Yes ]
    The evaluation will be made according to the score calculated on the basis of three evaluation scales: "Gastrointestinal Symptom Rating Scale "(GSRS), modified, provides a score ranging MIN=15/MAX=60; Extra-gastrointestinal symptoms evaluation scale, proposed on the basis of the symptoms most frequently observed in GS patients, provides a score ranging MIN=9/MAX=34; VQV scale proposed to evaluate the quality of life, provides a score ranging MIN=16/MAX=64. Total score can be no less than 37 (MIN) and not more than 146 (MAX), with a cut-off of 55.


Estimated Enrollment: 120
Study Start Date: June 2011
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: gluten
gluten is administered blindly versus placebo for 15 days at 10 g/day
Dietary Supplement: gluten
gluten is administered once a day at 10g/day for 15 days
Placebo Comparator: rice starch
placebo (rice starch) will be administered blindly versus gluten for 15 days at 10 g/day
Dietary Supplement: rice starch
rice starch is administered once a day at 10 g/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 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.
  Eligibility

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

Inclusion Criteria:

  • Adult patients with age between 18-65 with signs/symptoms compatible with gluten-triggered disorders
  • Patients testing negative for celiac disease either by biopsy Marsh 0-1 or those who are HLA-DQ2 and DQ8 negative, as well as tTG and EMA negative
  • Patients that improved on a gluten free diet

Exclusion Criteria:

  • Subjects diagnosed with celiac disease (positive TTG and/or EMA, and histology positive with Marsh II or above);
  • Subjects diagnosed with wheat allergy
  • Subjects with Type 1 Diabetes (T1D)
  • Subjects with Inflammatory Bowel Disease (ulcerative colitis or Crohn's disease)
  • Pregnancy
  • Subjects with Helicobacter Pylori infection and other gastrointestinal infection
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01485341

Contacts
Contact: Laura de Magistris, PhD +39-81-5665112 laura.demagistris@unina2.it

Locations
United States, Massachusetts
Center for Celiac Research & Treatment, Yawkey Center for Outpatients Care Recruiting
Boston, Massachusetts, United States, 02114
Contact: Stephanie S Camhi, Clinical Research Coordinator    617-643-9942    sscamhi@partners.org   
Principal Investigator: Alessio Fasano, MD         
Principal Investigator: Karen M Lammers, PhD         
Sub-Investigator: Stefania Senger, PhD         
Sub-Investigator: Gloria Serena, PhD student         
Italy
Università Politecnica delle Marche Recruiting
Ancona, Italy
Contact: Carlo Catassi, M.D., M.P.H.    39 071 596 23 64    catassi@tin.it   
Principal Investigator: Carlo Catassi, M.D., M.P.H.         
Gastroenterologia ed Endoscopia digestiva, Ospedale San Giuseppe Moscati Recruiting
Avellino, Italy
Contact: Nicola Giardullo, MD       ngiardu@tin.it   
Sub-Investigator: Gaetano Iaquinto, MD         
Sub-Investigator: Giuseppe Mazzarella, PhD         
Principal Investigator: Nicola Giardullo, MD         
Gastroenterology, Second University of Naples Recruiting
Naples, Italy, 80138
Contact: Maria Rosaria Amato, Nurse    +39-81-5665117    mariarosaria.amato@unina2.it   
Contact: Gabriele Riegler, MD    +39-81-5665116    gabriele.riegler@unina2.it   
Principal Investigator: Anna Sapone, MD, PhD         
Sub-Investigator: Gabriele Riegler, MD         
Sub-Investigator: Amalia Cirillo, MD         
Sub-Investigator: Angelo Pezzullo, MD         
Internal Medicine, Policlinico di Palermo Recruiting
Palermo, Italy
Contact: Antonio Carroccio, MD    +39-91-6552860    acarroccio@hotmail.com   
Contact: Pasquale Mansueto, MD    +39-91-6552860    pmansu@libero.it   
Principal Investigator: Antonio Carroccio, MD         
Sub-Investigator: Pasquale Mansueto, MD         
Gastroenterology, University of Salerno Completed
Salerno, Italy
Ospedale "Casa Sollievo della Sofferenza" - IRCCS - Recruiting
San Giovanni Rotondo (Foggia), Italy
Contact: Fabrizio Bossa, MD       f.bossa@operapadrepio.it   
Contact: Angelo Andriulli, MD       a.andriulli@operapadrepio.it   
Principal Investigator: Angelo Andriulli, MD         
Sub-Investigator: Fabrizio Bossa, MD         
Sub-Investigator: Rosalba Ricciardi, MD         
Sponsors and Collaborators
Second University of Naples
Investigators
Principal Investigator: Anna Sapone, MD, PhD Second University of Naples
  More Information

No publications provided

Responsible Party: Laura de Magistris, Senior Researcher, PhD, Second University of Naples
ClinicalTrials.gov Identifier: NCT01485341     History of Changes
Other Study ID Numbers: 61-2-9-2011
Study First Received: November 17, 2011
Last Updated: May 14, 2014
Health Authority: Italy: Ethics Committee

Keywords provided by Second University of Naples:
gluten sensitivity

ClinicalTrials.gov processed this record on September 14, 2014