Abstract / Summary
Abstract Background The threshold below which gluten is harmless for an individual with celiac disease has not been established. In its absence, guidelines recommend complete avoidance of gluten from all sources, including cross-contact with gluten, which in everyday life translates into continuous label-checking, control over food preparation, and heightened vigilance in social settings. This vigilance carries a substantial burden for dietary quality of life and can foster rigidity, avoidance, and food preoccupation, features recognized as risk factors for disordered eating. Existing threshold evidence derives from fixed-dose gluten capsule challenges, acute biomarker experiments, and retrospective syntheses, none of which corresponds to distributed, chronic, food-borne exposure with gluten coming from cross-contact evaluated against a histological endpoint. Whether the strictness currently demanded is proportionate to the physiological risk of low-level exposure therefore remains unanswered. Methods This single-center, single-blind, parallel-group pilot randomized controlled trial is embedded within a convergent parallel mixed methods design in which the qualitative strand carries equal methodological weight. Thirty adults with celiac disease in clinical remission are randomized 1:1 to a relaxed gluten-free diet permitting cross-contact up to 200 ppm, or to an optimized strict gluten-free diet, for 24 weeks. The primary endpoint is the villus height to crypt depth ratio from duodenal biopsies at baseline and week 24, assessed by a blinded histopathologist, with a margin of 0.4 units for a clinically meaningful deterioration. Secondary endpoints comprise serum tissue transglutaminase IgA, fecal gluten immunogenic peptides, symptom and acceptability measures, and estimated gluten exposure. Semi-structured interviews at five timepoints are analyzed by inductive–deductive content analysis. Integration proceeds through connected sampling, joint displays at weeks 12, 18, and 24, and meta-inference. Analyses are estimation-focused; an individual safety switch is triggered by serum tissue transglutaminase IgA above 10 U/mL (reference: < 7 U/mL). Discussion The trial provides the first prospective histological evaluation of deliberately relaxed gluten avoidance from cross-contact. It is designed to inform a definitive multicenter trial. Trial registration German Clinical Trials Register, DRKS00039577. Registered 3rd of June 2026