WASHINGTON – A simple dietary challenge may help identify nonceliac gluten sensitivity in patients with gastrointestinal functional disorders, results of the ongoing, randomized GLUTOX trial suggest.
Nonceliac gluten sensitivity is an emergent syndrome that causes mainly gastrointestinal symptoms and has been thought to be present in about 6% of the population. The problem is that there is no established or well-defined diagnostic flow chart to identify these patients, study author Dr. Luca Elli said at the annual Digestive Disease Week.
To determine whether gluten induces symptoms in patients responding positively to a gluten-free diet and identify those potentially affected by nonceliac gluten sensitivity, GLUTOX enrolled 100 adults with functional GI symptoms and placed them on a gluten-free diet for 21 days. Severity of symptoms was measured before and after the diet using a 10-cm visual analogue scale (VAS) and the 36-item Short Form Health Survey (SF-36).
Patients with at least a 3-cm improvement in baseline VAS were then double-blind, randomly assigned to gluten (5.6 g per day) or placebo capsules for 7 days, followed by a 7-day washout period, and then crossed over to another 7-day cycle of gluten or placebo capsules.
At baseline, the mean age was 38 years, 90% of patients were female, 55 had irritable bowel syndrome, 36 functional dyspepsia, and 9 had other unspecified functional nonspecific gastrointestinal symptoms by ROME III criteria.
Patients with celiac disease or a wheat allergy or who were on an ongoing gluten-free diet were excluded.
In all, 81 patients reported a symptomatic improvement from baseline after the 21-day gluten-free-diet (mean VAS 7.5 vs. 3.3; P value = .001), Dr. Elli, from Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan reported in a distinguished abstract plenary session.
“All of the symptoms we found were reduced by the gluten-free diet, but especially patient satisfaction about stool consistency, bloating, and the global satisfaction were improved in an important way,” he said.
Symptom improvements were also associated with significant improvements in the SF-36 physical component summary and mental component summary. Most responders were female (88%); 48 had irritable bowel syndrome, 25 dyspepsia, and 8 other.
After the gluten capsule challenge, 25 of the 81 gluten-free diet responders had a severe symptomatic relapse especially in stool consistency satisfaction, bloating, and abdominal pain, Dr. Elli said.
The relapses were also associated with a significant decrease in SF-36 physical and mental component summaries.
No demographic or biochemical parameters were significantly associated with a response to the gluten challenge, Dr. Elli said. Most of those having a response were female (96%); 13 had irritable bowel syndrome, 10 dyspepsia, and 2 other.
The sequence of the gluten and placebo capsules also had no effect on the results.
If the data are confirmed, it’s possible the double-blind challenge could be used to select gluten-free diet responders and inserted into the diagnostic flow chart for patients with gastrointestinal functional disorders, Dr. Elli said.
A very important open issue is also the 56% of enrolled subjects who responded to the gluten-free diet, but did not show symptoms with the gluten double-blind challenge, he added.
During a discussion of the results, attendees questioned whether the study design, particularly the failure to biopsy patients for celiac disease at enrollment and the short 7-day washout period, was sufficient to answer the question of identifying patients with nonceliac gluten sensitivity.
Session comoderator Dr. Bernd Schnabl, from University of California–San Diego, agreed that the study design was not ideal and that the study would have been strengthened by using biopsy to rule out patients with celiac disease. That said, the study represents a start.
“If we can stratify these patients and re-challenge them longer, it could be helpful in identifying a subpopulation of functional patients who might benefit from a gluten-free diet,” he said.
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