Gluten-free Diet in Gluten-genetically Predisposed Subjects

NCT00677495 | Completed

• 1 other identifier: RC 25/07
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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. 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. 2.to demonstrate the mucosal gluten-dependent immune response before and after 12 months of gluten-free diet
3. 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. 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

Keywords

Gluten-free diet; Celiac Disease; Genetic predisposition; Phage display library; Autoimmune diseases

Outcome Measures

Primary Outcomes (1)

• Intestinal mucosal gluten-dependent immune response before and after a gluten-free diet

  12 months

Study Arms (1)

Gluten-free diet

EXPERIMENTAL

Gluten-free diet

Dietary Supplement: Gluten-free diet

Interventions

Gluten-free diet DIETARY_SUPPLEMENT

Gluten-free diet

Gluten-free diet

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• first degree relatives of CD patients
• subjects with autoimmune disease tested negative for serum anti-tTG but positive for CD related HLA DQ2 or DQ8
• symptomatic subjects (genetically predisposed to gluten intolerance) tested negative for CD related autoantibodies and with apparently normal intestinal mucosa.

You may not qualify if:

• \- None

Sponsors & Collaborators

• IRCCS Burlo Garofolo: lead
• University of Trieste: collaborator
• Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia: collaborator
• University of Eastern Piedmont: collaborator

Study Sites (1)

IRCCS Burlo Garofolo

Trieste, Friuli Venezia Giulia, 34137, Italy

Location

Related Publications (2)

• Not T, Ziberna F, Vatta S, Quaglia S, Martelossi S, Villanacci V, Marzari R, Florian F, Vecchiet M, Sulic AM, Ferrara F, Bradbury A, Sblattero D, Ventura A. Cryptic genetic gluten intolerance revealed by intestinal antitransglutaminase antibodies and response to gluten-free diet. Gut. 2011 Nov;60(11):1487-93. doi: 10.1136/gut.2010.232900. Epub 2011 Apr 6.

  PMID: 21471568 RESULT

• De Leo L, Quaglia S, Ziberna F, Vatta S, Martelossi S, Maschio M, Not T. Serum anti-tissue transglutaminase antibodies detected during febrile illness may not be produced by the intestinal mucosa. J Pediatr. 2015 Mar;166(3):761-3. doi: 10.1016/j.jpeds.2014.12.005.

  PMID: 25722272 DERIVED

MeSH Terms

Conditions

Genetic Predisposition to Disease; Celiac Disease; Autoimmune Diseases

Interventions

Diet, Gluten-Free

Condition Hierarchy (Ancestors)

Disease Susceptibility; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Malabsorption Syndromes; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Fabiana Ziberna

  IRCCS Burlo Garofolo, Trieste, Italy

  PRINCIPAL INVESTIGATOR

• Serena Vatta

  IRCCS Burlo Garofolo, Trieste, Italy

  PRINCIPAL INVESTIGATOR

• Stefano Martelossi, MD

  IRCCS Burlo Garofolo, Trieste, Italy

  PRINCIPAL INVESTIGATOR

• Roberto Marzari

  University of Trieste

  PRINCIPAL INVESTIGATOR

• Fiorella Florian

  University of Trieste

  PRINCIPAL INVESTIGATOR

• Vincenzo Villanacci, MD

  Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

  PRINCIPAL INVESTIGATOR

• Daniele Sblattero

  Department of Medical Sciences, University of Eastern Pidmont, Novara, Italy

  PRINCIPAL INVESTIGATOR

• Alessandro Ventura, MD

  IRCCS Burlo Garofolo, Trieste, Italy

  STUDY CHAIR

• Tarcisio Not, MD

  IRCCS Burlo Garofolo, Trieste, Italy

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: May 12, 2008
• First Posted: May 14, 2008
• Study Start: May 1, 2007
• Primary Completion: December 1, 2019
• Study Completion: June 1, 2020
• Last Updated: September 3, 2020

Record last verified: 2020-09

Locations

IT (1)