Search for atoxic cereals: a single blind, cross-over study on the safety of a single dose of Triticum monococcum, in patients with celiac disease.

Background Cereals with absent or reduced toxicity are actively researched as alternative therapy to gluten-free diet (GFD) for patients with coeliac disease (CD). Triticum monococcum, an ancient wheat, is a potential candoidtae because of no toxicity in in-vitro and ex-vivo studies. The aim of our study was to investigate safety of administration of a single dose of gluten of Tm in patients with CD on GFD. Methods We performed a Phase II, single blind, cross-over study involving 12 CD patients adherent to GFD for at least 12 months assigned to be challenged at time 0, 14 and 28 days with a single fixed dose of 2.5 grams of the following (random order): rice (as reference atoxic protein), Amygluten (as reference toxic protein) and Tm dispersed in a gluten-free pudding. The primary end-point of the study was the change in intestinal permeability as assessed by changes of urinary lactulose/rhamnose ratio (L/R ratio) measured by HPLC. We also assessed the occurrence of gastrointestinal adverse events graded for intensity and duration according to the WHO scale. Variables were expressed as mean ± SEM; paired t-test and χ2 test were used as appropriate to compare continue and categorical variables. The study was approved by the local Ethic Committee and each patient signed a written informed consent. Results The urinary L/R ratio remained virtually the same during challenge with the 3 cereals, and was 0.058 ± 0.03 with rice, 0.048 ± 0.02 with Tm and 0.063 ± 0.015 with Amygluten. Gastrointestinal adverse events were 11, 8 and 31 with rice, Tm and Amygluten, respectively and in all cases events were graded as “mild” or “moderate” with rice and Tm, and as “severe” or “disabling” in 4 case during Amygluten. Conclusions The finding that Amygluten did not cause a significant change of urinary L/R indicates that the methodology is not sensitive enough for acute toxicity studies, and no conclusion can therefore be drown on safety of Tm. Tm was, however, well tolerated by all patients providing the rationale for further investigation on the safety of this cereal for CD patients.