title: Small Amounts of Gluten in Subjects With Suspected Nonceliac Gluten Sensitivity: A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Trial.
abstract: OBJECTIVE
  There is debate over the existence of nonceliac gluten sensitivity (NCGS) intestinal and extraintestinal symptoms in response to ingestion of gluten-containing foods by people without celiac disease or wheat allergy. We performed a randomized, double-blind, placebo-controlled, cross-over trial to determine the effects of administration of low doses of gluten to subjects with suspected NCGS.
  
  
  METHODS
  We enrolled 61 adults without celiac disease or a wheat allergy who believed ingestion of gluten-containing food to be the cause of their intestinal and extraintestinal symptoms. Participants were assigned randomly to groups given either 4.375 g/day gluten or rice starch (placebo) for 1 week, each via gastrosoluble capsules. After a 1-week gluten-free diet, participants crossed over to the other group. The primary outcome was the change in overall (intestinal and extraintestinal) symptoms, determined by established scoring systems, between gluten and placebo intake. A secondary outcome was the change in individual symptom scores between gluten vs placebo.
  
  
  RESULTS
  According to the per-protocol analysis of data from the 59 patients who completed the trial, intake of gluten significantly increased overall symptoms compared with placebo (P = .034). Abdominal bloating (P = .040) and pain (P = .047), among the intestinal symptoms, and foggy mind (P = .019), depression (P = .020), and aphthous stomatitis (P = .025), among the extraintestinal symptoms, were significantly more severe when subjects received gluten than placebo.
  
  
  CONCLUSIONS
  In a cross-over trial of subjects with suspected NCGS, the severity of overall symptoms increased significantly during 1 week of intake of small amounts of gluten, compared with placebo. Clinical trial no: ISRCTN72857280.
authors.affiliation: First Department of Internal Medicine, St Matteo Hospital Foundation, University of Pavia, Pavia, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Sabatino
authors.affiliation: Department of Medical and Surgical Sciences, St Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Volta
authors.affiliation: First Department of Internal Medicine, St Matteo Hospital Foundation, University of Pavia, Pavia, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Salvatore
authors.affiliation: First Department of Internal Medicine, St Matteo Hospital Foundation, University of Pavia, Pavia, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Biancheri
authors.affiliation: Department of Medical and Surgical Sciences, St Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Caio
authors.affiliation: Department of Medical and Surgical Sciences, St Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: De Giorgio
authors.affiliation: First Department of Internal Medicine, St Matteo Hospital Foundation, University of Pavia, Pavia, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Di Stefano
authors.affiliation: First Department of Internal Medicine, St Matteo Hospital Foundation, University of Pavia, Pavia, Italy. Electronic address: gr.corazza@smatteo.pv.it.
authors.forename: Gino R
authors.initials: GR
authors.lastname: Corazza
mesh_terms: D015746:Abdominal Pain / Q000139:chemically induced / Q000473:pathology; D000328:Adult; D018592:Cross-Over Studies; D003863:Depression / Q000139:chemically induced / Q000473:pathology; D004311:Double-Blind Method; D005260:Female; D005983:Glutens / Q000008:administration & dosage* / Q000009:adverse effects*; D006801:Humans; D006967:Hypersensitivity / Q000473:pathology*; D008607:Intellectual Disability / Q000139:chemically induced / Q000473:pathology; D008297:Male; D010919:Placebos / Q000008:administration & dosage; D011446:Prospective Studies; D012720:Severity of Illness Index; D013280:Stomatitis / Q000139:chemically induced / Q000473:pathology
chemical_list: D010919:Placebos; D005983:Glutens
keywords: Extraintestinal; Gluten; Intestinal; Nonceliac Gluten Sensitivity; Placebo