Nonceliac gluten sensitivity (NCGS) is characterized by gastrointestinal (GI) and systemic symptoms that occur soon after gluten ingestion and resolve when gluten is withdrawn [Di Sabatino A et al. Clin Gastroenterol Hepatol. 2015]. However, some question the existence of NCGS and the role of gluten. Other food components could be responsible, and there are no well-established, defined diagnostic criteria for NCGS.

Luca Elli, MD, PhD, Center for the Prevention and Diagnosis of Celiac Disease, Milan, Italy, presented the results of the multicenter Glutox Trial [NCT01864993], which was designed to determine if gluten is associated with symptoms in patients who respond to a gluten-free diet (GFD).

Glutox was an Italian double-blind placebo-controlled challenge (DBPCC) trial that enrolled patients (n = 100) from outpatient gastroenterologic services. Eligible patients included adults with functional GI symptoms (eg, irritable bowel syndrome, dyspepsia) based on the Rome III criteria for functional GI disorders. Patients with known celiac disease, wheat allergy, or ongoing GFD were excluded. Patients were evaluated for symptoms and global satisfaction with the SF-36 Health Survey Update and the visual analog scale (VAS).

After enrollment, patients followed a GFD for 21 days. Those who responded with a change in VAS ≥ 3 cm were randomly assigned to 7 days of gluten or placebo. Gluten was administered in 800-mg capsules, 7 capsules per day (5.6 g per day); placebo was an equivalent amount of rice starch. After a 7-day washout period, patients crossed over to the other treatment. Patients followed a GFD during the entire study. At study end, NCGS was defined as a change in VAS ≥ 3 cm for gluten vs placebo.

During the GFD before randomization, responders (n = 81) were identified as those with improvement in abdominal pain, stool consistency, bloating, postprandial fullness, early satiety, epigastric pain, or other symptoms and in the physical and mental component summaries of global satisfaction.

During the DBPCC portion of the trial, patients who received gluten experienced a significant reduction in global VAS score (P = .05). Patients who reacted positively to gluten during this portion of the trial had worsening of their abdominal pain, stool consistency satisfaction, and bloating, with a decrease in both the physical and mental component summary scores. These patients were considered to have potential NCGS (n = 25). No demographic or biochemical marker was identified that was associated with a positive response to the gluten challenge. There was no effect of capsule sequence. About half (13 of 25) of patients reacting to gluten in the DBPCC portion of the trial received gluten first and placebo second.

The demographics of patients at enrollment, those who responded to the GFD, and those who had potential NCGS were similar (Table 1).

The Glutox Trial is ongoing. Further investigation may answer some questions raised by this trial. It is not known if DBPCC can be used to select GFD responders or diagnostically investigate functional GI symptoms. Fifty-six percent of enrolled patients who responded to the GFD did not react to the gluten DBPCC, suggesting that they may be sensitive to other dietary components, which remain to be identified.