Double-Blind Randomized Clinical Trial: Gluten versus Placebo Rechallenge in Patients with Lymphocytic Enteritis and Suspected Celiac Disease

Mercè Rosinach, Fernando Fernández-Bañares, Anna Carrasco, Montserrat Ibarra, Rocío Temiño, Antonio Salas, Maria Esteve, Mercè Rosinach, Fernando Fernández-Bañares, Anna Carrasco, Montserrat Ibarra, Rocío Temiño, Antonio Salas, Maria Esteve

Abstract

Background: The role of gluten as a trigger of symptoms in non-coeliac gluten sensitivity has been questioned.

Aim: To demonstrate that gluten is the trigger of symptoms in a subgroup of patients fulfilling the diagnostic criteria for non-coeliac gluten sensitivity (NCGS), which presented with lymphocytic enteritis, positive celiac genetics and negative celiac serology.

Methods: Double-blind randomized clinical trial of gluten vs placebo rechallenge.

Inclusion criteria: >18 years of age, HLA-DQ2/8+, negative coeliac serology and gluten-dependent lymphocytic enteritis, and GI symptoms, with clinical and histological remission at inclusion. Eighteen patients were randomised: 11 gluten (20 g/day) and 7 placebo. Clinical symptoms, quality of life (GIQLI), and presence of gamma/delta+ cells and transglutaminase deposits were evaluated.

Results: 91% of patients had clinical relapse during gluten challenge versus 28.5% after placebo (p = 0.01). Clinical scores and GIQLI worsened after gluten but not after placebo (p<0.01). The presence of coeliac tissue markers at baseline biopsy on a gluten-free diet allowed classifying 9 out of the 18 (50%) patients as having probable 'coeliac lite' disease.

Conclusion: This proof-of-concept study indicates that gluten is the trigger of symptoms in a subgroup of patients fulfilling the diagnostic criteria for NCGS. They were characterized by positive celiac genetics, lymphocytic enteritis, and clinical and histological remission after a gluten-free diet.

Trial registration: ClinicalTrials.gov NCT02472704.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Flow of patient recruitment and…
Fig 1. Flow of patient recruitment and reasons for screening failure and withdrawals.
Fig 2. Evolution of the total clinical…
Fig 2. Evolution of the total clinical score throughout the study in individual patients of both gluten-treated and placebo groups.
Fig 3. Changes in clinical symptom visual…
Fig 3. Changes in clinical symptom visual analogue scales from baseline to the end of the study in the gluten-treated and placebo groups.
Total score represents the sum of values of the VAS of the different clinical symptoms. Results are expressed as mean±SEM.
Fig 4. Evolution of health-related quality of…
Fig 4. Evolution of health-related quality of life as assessed with the GIQLI in both gluten-treated and placebo groups.

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