Introduction

Gluten-related disorders include Celiac Disease (CD), Wheat Allergy (WA) and Non-Celiac Gluten Sensitivity (NCGS). NCGS is a syndrome characterized by the onset of intestinal and/or extra-intestinal symptoms after the ingestion of gluten-containing foods. Diagnosis is, firstly, based on the exclusion of CD and WA and on clinical response to a gluten-free diet (GFD). Furthermore, a single- or double-blind placebo-controlled gluten challenge is needed in order to limit placebo/nocebo effects. However, food challenges are time consuming and require dedicated health-professionals, but, according to Salerno Criteria, they are necessary to make a correct diagnosis of NCGS.

Aims & Methods

Our aim was to evaluate the efficacy of Test33, a new test, in NCGS diagnosis and to simplify the diagnostic procedure through its use in daily clinical practice. It is a self-administered commercially-available kit containing undistinguishable gluten and placebo capsules, identifiable through a unique code. The patients downloaded a mobile app, which guided them through the administration of the capsules during the blind challenge. Furthermore, the app allowed the self-assessment of symptoms by means of 33 10cm visual analogue scales (VAS), 10 for gastrointestinal symptoms and 23 for extraintestinal symptoms. After an initial three-week-long phase on a GFD, responsive patients were randomly assigned to the blind challenge. The challenge consisted of three different phases: gluten (5.6 g/day) or placebo capsules for seven days, followed by a one-week-long washout period (on GFD) and, finally, seven days of crossover period. We made a “Initial NCGS Diagnosis” after the GFD phase and a “Confirmed NCGS Diagnosis” after the challenge, following two different criteria, the second one less stringent. The primary endpoint was the worsening of symptoms (VAS increase ≥ 3 cm) during blind gluten ingestion compared to placebo.

Results

107 persons (88 females, 38.5 ± 15.6 years of age) agreed to participate. 97 (91%) completed the GFD period, while 88 (82%) completed the entire challenge. After 3 weeks on a GFD, 96.9% of participants reported significantly improved gastrointestinal (p<0.006) and extra-intestinal symptoms and higher general well-being (p<0.00001), resulting as responsive to GFD. During the blind challenge, general well-being score was significantly lower in the gluten group (p<0.027). Among gastrointestinal symptoms, abdominal pain (3.17 ± 0.32 vs 2.37 ± 0.30), constipation (3.27 ± 0.35 vs 2.38 ± 0.30), meteorism (5.40 ± 0.35 vs 3.68 ± 0.33), bloating (4.43 ± 0.31 vs 2.90 ± 0.30) and fullness (4.14 ± 0.36 vs 3.12 ± 0.33) were all worsened by blinded gluten ingestion (all p<0.039), while, regarding extra-intestinal symptoms, 13 out of 22 were significantly worsened after blind gluten ingestion (all p<0.04). None of the symptoms (both gastrointestinal and extra-intestinal) worsened during placebo assumption. The “Initial NCGS diagnosis” was made in 54.6% of the 97 participants who completed the GFD period, while the “Confirmed NCGS Diagnosis” was made only in 8 out of 88 patients (9.1%) who completed gluten challenge, following the more stringent criterion 1.

Conclusion

This self-administered blind gluten challenge supported by a dedicated app diagnosed NCGS among patients reporting symptoms after gluten intake. Therefore, Test33 may be a useful strategy for the assessment of symptoms (intestinal and extra-intestinal) strictly related to the blind gluten ingestion with less time and staff-consuming.
Its use may simplify NCGS diagnostic procedure in daily clinical practice.