Symptomatic Response to Gluten Challenge in Patients With Suspected Non Celiac Gluten Sensitivity (Glutox)

Glutox Trial. Symptomatic Response to Gluten Challenge in Patients With Suspected Non Celiac Gluten Sensitivity: a Double Blind Crossover Controlled Trial

Non Celiac Gluten Sensitivity (NCGS) is an emergent syndrome mainly inducing gastrointestinal symptoms. NCGS is suspected to be present in the 6% of the population and thus it represents an important issue in health care. Actually it remains difficult to diagnose and prove due to the lack of established criteria. The investigators intention is to establish a diagnostic flowchart to evaluate the real impact of NCGS in a cohort of patients suffering from functional gastrointestinal symptoms.

Study Overview

• Status: Completed
• Conditions: Non Celiac Gluten Sensitivity
• Intervention / Treatment: Dietary supplement: gluten; Dietary supplement: Placebo

Detailed Description

The proposed study has been designed to be a randomised double-blind multicenter clinical trial with crossover. The Coordinating Center will be the "Centro per la Prevenzione e la Diagnosi della Malattia Celiaca", Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milano. Secondary enrollment centers will be Italian Gastroenterology Units with outpatient services. Enrollment criteria will be diagnosis of irritable bowel syndrome (IBS) or functional dyspepsia. Patients with other functional gastrointestinal disorders will be included in the group "Functional non specific gastrointestinal symptoms".

After they give their written informed consent, patients will undergo the diagnostic work-up recommended in case of suspected irritable bowel symptoms/functional dyspepsia and aimed at the exclusion of CD or allergy to alimentary antigens by means of serological testing (anti transglutaminase antibodies) or skin tests, or other gastrointestinal diseases. Endoscopic, histologic and/or imaging exams together with supplemental blood tests will be prescribed on individual cases and according with the international guidelines.

Enrolled subjects will be asked to fill

• a checklist for the evaluation of the psychological profile (SCL90 questionnaire, with the particular aim of evaluating levels of anxiety, depression and somatisation);
• a questionnaire about the perceived level of physical and mental health (SF36 questionnaire);
• Ten centimeters long visual analogue scales (VAS) on the level of satisfaction with their health status and on the intensity of the single symptoms.

At the end of the present phase patients will start a GFD for the subsequent three weeks.

At the end of the GFD period patients will fill VAS and SF36. Only those patients presenting a 30% increase of the global VAS score ("GFD Responders") will continue the study. Conversely, non responders will be considered "non gluten sensitive" and they will finish the trial.

Responders to the GFD period will entry the randomisation phase and will undergo a double-blind stimulation test with cross over. Patients will be randomised to assume gluten or placebo for 7 days. After the treatment patients will fill VAS and SF36.

A diagnosis of NCGS will be ascertained in case of symptomatic response limited to gluten ingestion.

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Crema, Italy, 26013
    • Ospedale Maggiore di Crema
  • Feltre, Italy, 32032
    • Ospedale S. Maria
  • Reggio Emilia, Italy, 42122
    • Arcispedale S. Maria nuova
  • Lombardia
    • Busto Arsizio, Lombardia, Italy
      • Ospedale di Busto Arsizio
    • Como, Lombardia, Italy
      • Ospedale Valduce di Como

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects with gastrointestinal functional disorders (irritable bowel syndrome, functional dyspepsia or unspecified functional gastrointestinal symptoms)

Exclusion Criteria:

• Celiac disease
• Alimentary allergies
• Inflammatory bowel disease
• Major abdominal surgery
• Psychiatric disorders
• Neoplasia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: suspected NC gluten sensitive subjects; Patients referring gastrointestinal functional disorders will be selected and they will follow a gluten free diet	Dietary supplement: gluten; The enrolled patients will be invited to follow a gluten free diet. Patients responsive to the diet will be invited to assume gluten or placebo following a double blind with cross over scheme; Dietary supplement: Placebo; Patients responsive to the diet will be invited to blindly assume gluten or placebo following a double blind with cross over scheme
Experimental: suspected NC gluten sensitive; Patients referring gastrointestinal functional disorders will be selected and they will follow a gluten free diet	Dietary supplement: gluten; The enrolled patients will be invited to follow a gluten free diet. Patients responsive to the diet will be invited to assume gluten or placebo following a double blind with cross over scheme; Dietary supplement: Placebo; Patients responsive to the diet will be invited to blindly assume gluten or placebo following a double blind with cross over scheme

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Scores on the Visual Analogue Scales	Symptomatic resolution after the instauration of a gluten free diet will be verified by means of VAS scales	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life	patients with non celiac gluten sensitivity will be evaluated by means of SF36 questionnaire	28 days

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
• Investigators: Principal Investigator: Luca Elli, MD, PhD, Center for Prevention and Diagnosis of Celiac Disease, Fondazione IRCCS Cà Granda

Publications and helpful links

General Publications

• Scricciolo A, Lombardo V, Elli L, Bascunan KA, Doneda L, Rinaldi F, Pinto D, Araya M, Costantino A, Vecchi M, Roncoroni L. Use of a proline-specific endopeptidase to reintroduce gluten in patients with non-coeliac gluten sensitivity: A randomized trial. Clin Nutr. 2022 Sep;41(9):2025-2030. doi: 10.1016/j.clnu.2022.07.029. Epub 2022 Jul 31.

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: May 19, 2013
• First Submitted That Met QC Criteria: May 26, 2013
• First Posted (Estimate): May 30, 2013

Study Record Updates

• Last Update Posted (Estimate): February 24, 2016
• Last Update Submitted That Met QC Criteria: February 22, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: irritable bowel syndrome; non celiac gluten sensitivity; gluten; functional disorders
• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity
• Other Study ID Numbers: 1876/2012; 1876 (Other Identifier: Fondazione IRCCS Cà Granda)