A prospective, double-blind, placebo-controlled trial to establish a safe gluten threshold for patients with celiac disease.
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.
Catassi
Carlo
C
Center For Celiac Research, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Fabiani
Elisabetta
E
Iacono
Giuseppe
G
D'Agate
Cinzia
C
Francavilla
Ruggiero
R
Biagi
Federico
F
Volta
Umberto
U
Accomando
Salvatore
S
Picarelli
Antonio
A
De Vitis
Italo
I
Pianelli
Giovanna
G
Gesuita
Rosaria
R
Carle
Flavia
F
Mandolesi
Alessandra
A
Bearzi
Italo
I
Fasano
Alessio
A
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
D001323:Autoantibodies; D005983:Glutens