Gluten-free Diet in Gluten-genetically Predisposed Subjects

Summary

Undetected or untreated CD may cause severe complications later in life, such as autoimmune disorders.

It is recommended for subjects with autoimmune diseases or at risk for CD to be screened for CD and to repeat serological screening about every three years to detect cases of clinically silent, late-onset CD.

Celiac disease (CD) auto-antibodies against tissue transglutaminase (anti-tTG) are produced in the intestinal mucosa even when not measurable in serum. By using the phage display libraries technique it is possible to investigate in vivo (intestinal biopsy) early antibody responses in autoimmune disease. In particularly, this technique demonstrated that the humoral response against tissue transglutaminase occurs at the intestinal mucosal level, and that the human VH5 gene is the commonly used variable region by the celiac patients to build the anti-tTG. The intestinal mucosa production of IgA anti-tTG could be important in the diagnostic work-up of early-stage CD, when mucosal histology is not yet diagnostic.

The investigators propose to 1) first degree relatives of CD patients, 2) subjects with autoimmune disease, 3) symptomatic subjects (genetically predisposed to gluten intolerance) tested negative for CD related autoantibodies and with apparently normal intestinal mucosa a prospective study to uncover early-stage of gluten intolerance by measuring the mucosal VH5 restricted gene family anti-tTG clones in two biopsies: before and after one year of gluten free-diet (GFD).

Aims of this clinical trial are:

1. to measure by means of phage display libraries the gluten dependent humoral immune response (anti-tTG) of the intestinal mucosa in subjects with high risk of untreated CD, without CD-related intestinal lesions.
2. to demonstrate the mucosal gluten-dependent immune response before and after 12 months of gluten-free diet
3. to demonstrate that dietary intervention might modify the clinical condition (e.g improvements of the gastrointestinal complaints or extra-gastrointestinal symptoms) of the enrolled patients and the improvement of the intestinal inflammation with the disappearance of the mucosal anti-tTG.
4. to evaluate the specificity of the double staining technique for detecting IgA antitransglutaminase mucosal deposit with the phage display antibodies assay

Conditions

• Genetic Predisposition to Disease
• Celiac Disease

Interventions

DIETARY_SUPPLEMENT

Gluten-free diet

Gluten-free diet

Sponsors & Collaborators

• University of Trieste

  collaborator OTHER

• Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

  collaborator OTHER

• University of Eastern Piedmont

  collaborator OTHER

• IRCCS Burlo Garofolo

  lead OTHER

Principal Investigators

• Fabiana Ziberna · IRCCS Burlo Garofolo, Trieste, Italy

• Serena Vatta · IRCCS Burlo Garofolo, Trieste, Italy

• Stefano Martelossi, MD · IRCCS Burlo Garofolo, Trieste, Italy

• Roberto Marzari · University of Trieste

• Fiorella Florian · University of Trieste

• Vincenzo Villanacci, MD · Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

• Daniele Sblattero · Department of Medical Sciences, University of Eastern Pidmont, Novara, Italy

• Alessandro Ventura, MD · IRCCS Burlo Garofolo, Trieste, Italy

• Tarcisio Not, MD · IRCCS Burlo Garofolo, Trieste, Italy

Study Design

Allocation

NA

Purpose

DIAGNOSTIC

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2007-05-31

Primary Completion

2019-12-31

Completion

2020-06-30

Countries

• Italy

Study Locations