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). Design: 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 >= 2 y. The background daily gluten intake was maintained at < 5 mg. After a baseline evaluation (to), 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 to and after the gluten microchallenge (t(1)). Results: At to, 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.