title: A prospective, double-blind, placebo-controlled trial to establish a safe gluten threshold for patients with celiac disease.
abstract: BACKGROUND
  Treatment of celiac disease (CD) is based on the avoidance of gluten-containing food. However, it is not known whether trace amounts of gluten are harmful to treated patients.
  
  
  OBJECTIVE
  The objective was to establish the safety threshold of prolonged exposure to trace amounts of gluten (ie, contaminating gluten).
  
  
  METHODS
  This was a multicenter, double-blind, placebo-controlled, randomized trial in 49 adults with biopsy-proven CD who were being treated with a gluten-free diet (GFD) for > or =2 y. The background daily gluten intake was maintained at < 5 mg. After a baseline evaluation (t0), patients were assigned to ingest daily for 90 d a capsule containing 0, 10, or 50 mg gluten. Clinical, serologic, and histologic evaluations of the small intestine were performed at t0 and after the gluten microchallenge (t1).
  
  
  RESULTS
  At t0, the median villous height/crypt depth (Vh/Cd) in the small-intestinal mucosa was significantly lower and the intraepithelial lymphocyte (IEL) count (x 100 enterocytes) significantly higher in the CD patients (Vh/Cd: 2.20; 95% CI: 2.11, 2.89; IEL: 27; 95% CI: 23, 34) than in 20 non-CD control subjects (Vh/Cd: 2.87; 95% CI: 2.50, 3.09; IEL: 22; 95% CI: 18, 24). One patient (challenged with 10 mg gluten) developed a clinical relapse. At t(1), the percentage change in Vh/Cd was 9% (95% CI: 3%, 15%) in the placebo group (n = 13), -1% (-18%, 68%) in the 10-mg group (n = 13), and -20% (-22%, -13%) in the 50-mg group (n = 13). No significant differences in the IEL count were found between the 3 groups.
  
  
  CONCLUSIONS
  The ingestion of contaminating gluten should be kept lower than 50 mg/d in the treatment of CD.
authors.affiliation: Center For Celiac Research, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Carlo
authors.initials: C
authors.lastname: Catassi
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Fabiani
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Iacono
authors.forename: Cinzia
authors.initials: C
authors.lastname: D'Agate
authors.forename: Ruggiero
authors.initials: R
authors.lastname: Francavilla
authors.forename: Federico
authors.initials: F
authors.lastname: Biagi
authors.forename: Umberto
authors.initials: U
authors.lastname: Volta
authors.forename: Salvatore
authors.initials: S
authors.lastname: Accomando
authors.forename: Antonio
authors.initials: A
authors.lastname: Picarelli
authors.forename: Italo
authors.initials: I
authors.lastname: De Vitis
authors.forename: Giovanna
authors.initials: G
authors.lastname: Pianelli
authors.forename: Rosaria
authors.initials: R
authors.lastname: Gesuita
authors.forename: Flavia
authors.initials: F
authors.lastname: Carle
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mandolesi
authors.forename: Italo
authors.initials: I
authors.lastname: Bearzi
authors.forename: Alessio
authors.initials: A
authors.lastname: Fasano
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood; D002446:Celiac Disease / Q000097:blood / Q000178:diet therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005983:Glutens / Q000008:administration & dosage* / Q000009:adverse effects* / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D007421:Intestine, Small / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D001323:Autoantibodies; D005983:Glutens