Clinical Trial: Gluten-free Diet in Gluten-genetically Predisposed Subjects
Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional
Official Title: Usefulness of Gluten-free Diet in Gluten-genetically Predisposed Subjects Positive to Intestinal-mucosa Anti-transglutaminase Antibodies
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:
- to measure by means of phage display libraries the gluten dependent humoral immune response (anti-tTG) of the intestinal mucosa in subj
Detailed Summary:
Celiac disease (CD) is an autoimmune enteropathy triggered by ingestion of gluten in genetically susceptible subjects and is one of the most frequently occurring, treatable, lifelong disorders. In this disease we recognize the trigger (gluten), the genetic factor (HLA DQ2/8), the auto-antigen (the tissue-transglutaminase enzyme) and the auto-antibodies (IgA-IgG anti-transglutaminase) which are produced by the intestinal mucosa B lymphocytes (Gastroenterology 2000;119:234, J Immunol 2001;166:4170). Undetected or untreated, CD may cause more severe complications later in life, such as autoimmune disorders. Clear evidence exists of gluten-related autoimmunity in genetically predisposed patients (presence of the HLA DQ2/8). It has been shown that autoimmune disorders involving organs other than intestine (such as pancreas, cerebellum, liver, skin) could develop in unrecognized and/or untreated celiac subjects because of a persistent exposure to gluten. Presently, the additional risk for autoimmune diseases is estimated at 1.1% for each year without diagnosis (Gastroenterology 1999;117:297). Furthermore, when on a diet containing gluten, some CD patients produced organ-specific auto-antibodies (GAD, ICA, TPO, anti-Purkinje cells, cardiac auto-antibodies) which were not CD related and which disappeared after 6 to 12 months of gluten-free diet (J Pediatr 2000;137:263; Lancet 1996;347:369; Circulation 2002;105:2611). Bearing these data in mind, an early diagnosis of CD might have prevented some CD patients from developing an autoimmune disease such as type 1 diabetes or thyroiditis. In view of these observations, 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. In other words, there are gluten-genetically predisposed subjects (tested positive for HLA DQ2/8) - testing nega
Sponsor: IRCCS Burlo Garofolo
Current Primary Outcome: Intestinal mucosal gluten-dependent immune response before and after a gluten-free diet [ Time Frame: 12 months ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
Original Secondary Outcome:
Information By: IRCCS Burlo Garofolo
Dates:
Date Received: May 12, 2008
Date Started: May 2007
Date Completion: December 2017
Last Updated: March 8, 2017
Last Verified: March 2017
