EFFECTS OF MODIFIED WHEAT GLUTEN ADMINISTRATION IN PATIENTS WITH CELIAC DISEASE: RESULTS OF A DOUBLE-BLIND, GLUTEN-CONTROLLED CLINICAL TRIAL

Background and aim: The treatment of celiac disease (CD) is based on a lifelong gluten‐free diet (GFD). Recent studies showed that biochemical modifications of gluten peptides, induced by microbial transglutaminase (mTG) on wheat flour in the presence of lysine ethyl ester (K‐C2‐H5), inhibit in vitro their ability to induce the CDspecific immune response. Our aim was to perform a double‐blind, gluten‐controlled clinical trial to evaluate the safety of a protracted ingestion of mTG‐modified wheat flour in CD patients. Material and methods: Twenty‐two but 1 CD patients in remission were randomized to receive, in double blind, rusks made with either mTG‐modified (Code A, n = 11) or unmodified (Code B, n = 10) wheat flour. Every month for a total of 3 months, patients were asked to complete an anamnestic card to monitor symptoms using a 100‐ mm visual analogue scale (VAS), with 0 representing the absence of symptoms. Serum anti‐tissue transglutaminase (anti‐tTG) and endomysium antibodies (EMA), as well as creatinine concentration were also monitored. At the end of the study, patients underwent upper endoscopy with biopsy for duodenal histology and organ culture system. Results: Five out of 11 patients who received rusks of Code A and 6 out of 10 patients who received rusks of Code B completed the study. At baseline, all patients who completed the study showed serum anti‐tTG and EMA negative results. At the end of the study, one out of 5 (20%) patients ingesting rusks of Code A and 4 out of 6 (66.7%) patients taking rusks of Code B presented serum anti‐tTG and EMA positive results. In patients who received rusks of Code B, anti‐tTG serum levels determined after treatment were significantly higher (p=0.0313) than those measured at baseline. No significant change was found in the creatinine serum levels after treatment of all patients who completed the study. At the end of the study, one out of 5 (20%) patients ingesting rusks of Code A and 4 out of 6 (66.7%) patients taking rusks of Code B presented intestinal villous atrophy. Consistently, anti‐tTG duodenal levels determined in patients who received rusks of Code B tended to be higher than those measured in patients who ate rusks of Code A. Swelling, meteorism and nausea tended to be more severe in patients ingesting rusks of Code B than those taking rusks of Code A. Conclusions: If data are confirmed, the enzymatic treatment of wheat flour induced by mTG in the presence of K‐C2‐H5 could become one of the most promising strategies for CD treatment alternative to the GFD.