Identification of Gluten Sensitivity in Irritable Bowel Syndrome (IBS-NCGS)

Double Blind Randomized Clinical Trial in Subjects With Irritable Bowel Syndrome for the Identification of Gluten Sensitivity

The aim of our study will be to establish in how many subjects with gastrointestinal symptoms and previous diagnosis of irritable bowel syndrome (IBS), the clinical picture is attributable to non celiac gluten sensitivity (NCGS) or fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) intolerance. For this purpose, all subjects with IBS will take a low FODMAPs diet, which implies the absence of cereals and consequently of gluten, and those presenting symptom improvement during this dietary treatment, will be exposed to a double-blind gluten or placebo challenge, to make a diagnosis of NCGS.

Study Overview

• Status: Completed
• Conditions: Irritable Bowel Syndrome; Non-celiac Gluten Sensitivity
• Intervention / Treatment: Dietary supplement: diet containing gluten; Dietary supplement: Diet containing placebo

Detailed Description

Study design:

For this study, patients with diagnosis of IBS performed by Rome IV criteria and followed as outpatients at the Clinical Nutrition Clinic of "Petrucciani" Nursing Home of Lecce (LE), Italy, will be enrolled.

At baseline, the enrolled subjects will follow a balanced normal-caloric low-FODMAP and gluten-free diet for a period of 4 weeks. At the end of the 4 weeks patients who did not experience an improvement in symptoms will be considered "non-responders" and discontinue the clinical trial. Only those subjects who had showed a significant improvement in symptoms, will be enrolled for the phase 2 of the study that includes a challenge with gluten or with placebo, as described by the Salerno criteria.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • BA
    • Bari, BA, Italy, 70124
      • Michele Barone

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• a gluten-containing diet for at least six months before enrollment
• anti-transglutaminase antibodies (IgA and IgG) absence
• normal serum IgA levels
• prick and specific IgE tests for wheat allergy negative

Exclusion Criteria:

• celiac disease
• wheat allergy
• chronic intestinal inflammatory diseases
• psychiatric disorders
• major abdominal surgery (in particular intestinal resections)
• diabetes mellitus
• previous anaphylactic episodes
• gluten-free diet in the previous six months
• pregnant or lactating women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: patients with IBS treated with gluten; patients receiving gluten	Dietary supplement: diet containing gluten; gluten will be added for 7 days to the low FODMAP/gluten free diet diet. After 1 week of wash-out, patients will switch (cross-over) to placebo for another 7 days
Placebo Comparator: patients with IBS treated with placebo; patients receiving placebo	Dietary supplement: Diet containing placebo; Placebo will be added for 7 days to the low FODMAP/gluten free diet diet. After 1 week of wash-out, patients will switch (cross-over) to gluten for another 7 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of FODMAP intollerance in IBS subjects	To evaluate the FODMAP intolerance, the response to a low FODMAP diet will be assessed by a visual analogue scale (VAS) before and after the dietary challenge. The VAS scale consists in is a straight horizontal line of fixed length, usually 100 mm. The ends are defined as the extreme limits of the parameter to be measured (symptoms, pain, subjective feeling of well-being/malaise) orientated from the left (worst) to the right (best) The patient is invited to indicate a position (a point) along the line.	4 weeks
Identification of NCGS in IBS subjects who responded to low FODMAPs diet	To evaluate the NCGS, the response to the gluten challenge will be assessed by a visual analogue scale (VAS) before and after the dietary challenge. The VAS scale consists in is a straight horizontal line of fixed length, usually 100 mm. The ends are defined as the extreme limits of the parameter to be measured (symptoms, pain, subjective feeling of well-being/malaise) orientated from the left (worst) to the right (best) The patient is invited to indicate a position (a point) along the line.	3 weeks

Collaborators and Investigators

• Sponsor: University of Bari
• Investigators: Study Director: Michele Barone, University of Bari

Publications and helpful links

General Publications

• Carroccio A, Rini G, Mansueto P. Non-celiac wheat sensitivity is a more appropriate label than non-celiac gluten sensitivity. Gastroenterology. 2014 Jan;146(1):320-1. doi: 10.1053/j.gastro.2013.08.061. Epub 2013 Nov 22. No abstract available.
• Catassi C, Elli L, Bonaz B, Bouma G, Carroccio A, Castillejo G, Cellier C, Cristofori F, de Magistris L, Dolinsek J, Dieterich W, Francavilla R, Hadjivassiliou M, Holtmeier W, Korner U, Leffler DA, Lundin KE, Mazzarella G, Mulder CJ, Pellegrini N, Rostami K, Sanders D, Skodje GI, Schuppan D, Ullrich R, Volta U, Williams M, Zevallos VF, Zopf Y, Fasano A. Diagnosis of Non-Celiac Gluten Sensitivity (NCGS): The Salerno Experts' Criteria. Nutrients. 2015 Jun 18;7(6):4966-77. doi: 10.3390/nu7064966.
• Drossman DA. Functional Gastrointestinal Disorders: History, Pathophysiology, Clinical Features and Rome IV. Gastroenterology. 2016 Feb 19:S0016-5085(16)00223-7. doi: 10.1053/j.gastro.2016.02.032. Online ahead of print.
• Catassi C, Alaedini A, Bojarski C, Bonaz B, Bouma G, Carroccio A, Castillejo G, De Magistris L, Dieterich W, Di Liberto D, Elli L, Fasano A, Hadjivassiliou M, Kurien M, Lionetti E, Mulder CJ, Rostami K, Sapone A, Scherf K, Schuppan D, Trott N, Volta U, Zevallos V, Zopf Y, Sanders DS. The Overlapping Area of Non-Celiac Gluten Sensitivity (NCGS) and Wheat-Sensitive Irritable Bowel Syndrome (IBS): An Update. Nutrients. 2017 Nov 21;9(11):1268. doi: 10.3390/nu9111268.
• Van den Houte K, Carbone F, Pannemans J, Corsetti M, Fischler B, Piessevaux H, Tack J. Prevalence and impact of self-reported irritable bowel symptoms in the general population. United European Gastroenterol J. 2019 Mar;7(2):307-315. doi: 10.1177/2050640618821804. Epub 2018 Dec 22.
• Jones AL. The Gluten-Free Diet: Fad or Necessity? Diabetes Spectr. 2017 May;30(2):118-123. doi: 10.2337/ds16-0022. No abstract available.
• Calasso M, Francavilla R, Cristofori F, De Angelis M, Gobbetti M. New Protocol for Production of Reduced-Gluten Wheat Bread and Pasta and Clinical Effect in Patients with Irritable Bowel Syndrome: A randomised, Double-Blind, Cross-Over Study. Nutrients. 2018 Dec 2;10(12):1873. doi: 10.3390/nu10121873.
• Junker Y, Zeissig S, Kim SJ, Barisani D, Wieser H, Leffler DA, Zevallos V, Libermann TA, Dillon S, Freitag TL, Kelly CP, Schuppan D. Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4. J Exp Med. 2012 Dec 17;209(13):2395-408. doi: 10.1084/jem.20102660. Epub 2012 Dec 3.
• Barone M, Gemello E, Viggiani MT, Cristofori F, Renna C, Iannone A, Di Leo A, Francavilla R. Evaluation of Non-Celiac Gluten Sensitivity in Patients with Previous Diagnosis of Irritable Bowel Syndrome: A Randomized Double-Blind Placebo-Controlled Crossover Trial. Nutrients. 2020 Mar 6;12(3):705. doi: 10.3390/nu12030705.

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2019
• Primary Completion (Actual): September 30, 2019
• Study Completion (Actual): October 30, 2019

Study Registration Dates

• First Submitted: July 8, 2019
• First Submitted That Met QC Criteria: July 11, 2019
• First Posted (Actual): July 12, 2019

Study Record Updates

• Last Update Posted (Actual): December 27, 2019
• Last Update Submitted That Met QC Criteria: December 24, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: gluten free diet; gastrointestinal symptoms; FODMAPs
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Immune System Diseases; Disease; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Hypersensitivity; Syndrome; Irritable Bowel Syndrome
• Other Study ID Numbers: Policlinic Hospital 5, Bari

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No