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 > or = 2 y. The back ground daily gluten intake was mainained 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, serologica, and histologic evaluations of the small intestine were performed at t0 and after the gluten microhallenge (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 percentate change in Vh/Cd was 9% 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. CONCLUSINS: The ingestion of contaminating gluten should be kept lower then 50 mg/d in the treatment of CD.