Brief Summary

An emerging problem in clinical practice is how to manage the growing number of patients who experience symptoms related to the ingestion of gluten-containing foods gluten and in whom celiac disease has been ruled out. These patients most frequently report gastrointestinal symptoms such as diarrhea, abdominal discomfort or pain, bloating, flatulence, but also extraintestinal symptoms, including headache, lethargy, attention-deficit/hyperactivity disorder, ataxia, or recurrent oral ulceration. This heterogeneous syndrome, which has been reported to improve or even disappear after gluten withdrawal and to relapse after gluten challenge, is called non-celiac gluten sensitivity.1 The concept of nonceliac gluten sensitivity is not completely new. Besides several sporadic single cases reported, more than 30 years ago an oral, double-blind, placebo-controlled, cross-over gluten challenge trial showed that six out of eight adult non-celiac patients, who suffered from intestinal symptoms caused by the ingestion of gluten-containing food, were affected by gluten-sensitive diarrhea. Over the last few years, an intense debate about the existence and the prevalence of nonceliac gluten sensitivity has emerged, as shown by the considerable increase in internet forums of discussion on this topic and in availability of gluten-free food. A definition of nonceliac gluten sensitivity based on definitive scientific evidence does not still exist, and the clinical trials conducted so far in order to fill this knowledge gap are burdened by a number of biases. In a cross-over trial of subjects with suspected NCGS, the severity of overall (intestinal plus extraintestinal) symptoms increased significantly during 1 week of intake of small amounts of gluten (daily 4.375 grams), compared with placebo. Among the 59 participants in this trial, the Investigatotors identified only three true gluten-sensitive patients, defined as having a delta overall score -calculated by subtracting the weekly overall score under placebo from that under gluten- higher than the mean delta overall score plus 2 standard deviations. However, these results should be cautiously interpreted due to the lack of a control group of non-gluten-sensitive subjects. On this basis, the Investigators will conduct a randomized, dose-finding, double-blind, placebo-controlled, cross-over gluten challenge trial aimed at comparing the effects of a daily dose of 8.4 grams of gluten with those of a daily dose of 6.0 or 4.2 grams of gluten on a cohort of subjects with nonceliac gluten sensitivity versus healthy volunteers.

Trial Health

At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date

Enrollment

840

participants targeted

Target at P75+ for not_applicable

Timeline

Completed

Started Jun 2017

Longer than P75 for not_applicable

Geographic Reach

1 country

1 active site

Status

unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

3.5 years study duration

First Submitted

Initial submission to the registry

June 13, 2017

Completed

Same day until next milestone

Study Start

First participant enrolled

June 13, 2017

Completed

2 days until next milestone

First Posted

Study publicly available on registry

June 15, 2017

Completed

2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 13, 2019

Completed

1.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 13, 2020

Completed

Last Updated

August 10, 2018

Status Verified

August 1, 2018

Enrollment Period

2 years

First QC Date

June 13, 2017

Last Update Submit

August 9, 2018

Conditions

Nonceliac Gluten Sensitivity

Keywords

dose-findingextraintestinal symptomsglutenintestinal symptomsplacebo

Outcome Measures

Primary Outcomes (1)

Change in delta overall (intestinal plus extraintestinal) score in nonceliac gluten sensitivity
The change in delta overall (intestinal plus extraintestinal) score, calculated by subtracting the 5-day overall score under placebo from the 5-day overall score under gluten, between the highest daily intake of gluten (8.4 grams) and the lowest ones (either 6.0 or 4.2 grams) in nonceliac gluten sensitivity.
18 months

Secondary Outcomes (4)

The change in individual symptom scores between the 5-day treatment with gluten and the 5-day treatment with placebo
18 months
The identification of patients with true nonceliac gluten sensitivity
18 months
Laboratory parameters as predictors of true nonceliac gluten sensitivity
24 months
Change in delta overall (intestinal plus extraintestinal) score between the highest daily intake of gluten (8.4 grams) and the lowest ones (either 6.0 or 4.2 grams) in healthy volunteers
24 months

Study Arms (12)

1A - NCGS

ACTIVE COMPARATOR

Seventy subjects with nonceliac gluten sensitivity will be given 14 gastrosoluble capsules containing purified wheat gluten corresponding to a daily gluten intake of 8.4 grams for five days. At the end of the first five day-long treatment, subjects will continue only their wash-out from gluten for two weeks, without taking any capsule. At T3, individuals will be given 14 daily gastrosoluble capsules containing placebo (rice starch) for five days. In both first and second five day-long treatment the 14 capsules will be ingested in no more than two times using a glass of water over the day.