Nonceliac Gluten SensitivityRAPLAGENCT03188367
Dose-finding Gluten Challenge Trial in Nonceliac Gluten-sensitivity
A study of Nonceliac Gluten Sensitivity, run by Antonio Di Sabatino at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Nonceliac Gluten Sensitivity
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 840 participants
- Where
- 1 siteItaly
- Study dates
- 13 Jun 2017to 13 Dec 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- persistence of relevant intestinal and extraintestinal symptoms believed by them to be caused by the ingestion of food containing even low doses of gluten
Who cannot join
- celiac disease
- wheat allergy
- intolerance to further food source of fermentable oligo- and disaccharides, monosaccharides and polyols
- lactose intolerance
- Helicobacter pylori infection
- giardiasis
Show all 14Show fewer
- inflammatory bowel disease
- cirrhosis
- excessive alcohol intake
- intake of nonsteroidal anti-inflammatory agents
- use of systemic immunosuppressant medication
- poorly controlled psychiatric disease
- pregnancy
- patients unable to give written informed consent will be excluded
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Fondazione IRCCS Policlinico San Matteo
Pavia, Pv, 27100
About this study
Official title: Randomized, Dose-finding, Double-blind, Placebo-controlled, Crossover Gluten Challenge Trial in Subjects With Nonceliac Gluten-sensitivity
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.
Read the detailed description
The Investigators will consecutively enroll adult patients referred to outpatients' Clinics of 21 Centres because of persistence of relevant intestinal and extraintestinal symptoms believed by them to be caused by the ingestion of food containing even low doses of gluten. In their clinical management patients in gluten-containing diet since at least two months will undergo ad hoc tests including serum determination of IgA anti-tissue transglutaminase and anti-endomysial antibodies, IgG anti-gliadin antibodies (AGA), total IgA and IgE, wheat-specific IgE, upper endoscopy with collection of multiple duodenal biopsies, HLA genotyping, fecal calprotectin and lactose breath test. The Investigators will investigate serum AGA IgG since they have been detected in some patients with "suspected" nonceliac gluten sensitivity. Patients with celiac disease, wheat allergy, intolerance to further food source of fermentable oligo- and disaccharides, monosaccharides and polyols, lactose intolerance, Helicobacter pylori infection, giardiasis, inflammatory bowel disease, cirrhosis, excessive alcohol intake, intake of nonsteroidal anti-inflammatory agents, use of systemic immunosuppressant medication, poorly controlled psychiatric disease, pregnancy and those unable to give written informed consent will be excluded. The Investigators will also recruit as control group 420 age- and sex-matched healthy volunteers, undergoing IgG AGA and all negative for anti-tissue transglutaminase antibodies. Healthy volunteers will not be affected by any comorbidity and food intolerance.
Each Centre will enroll 20 patients with suspected nonceliac gluten sensitivity and 20 healthy volunteers. Recruitment of patients and, at greater extent, healthy volunteers should not be an issue as the 21 Centres involved in this trial are well-known for diagnosis and treatment of gluten-related disorders. The Investigators will consider drop-outs from the study all the patients who will fail to attend even a single appointment or test in the trial. Moreover, compliance with the study treatment will be assessed by unused capsule counts at T2 and T4. Compliance with the gluten-free diet at each time point will be assessed through a validated questionnaire. To exclude the possibility of patients being able to discriminate between gluten capsules and placebo capsules, we preliminarily tested capsule recognition in a group of 20 healthy volunteers. On two different days, healthy volunteers were asked to take capsules and then clearly state if the capsules contained gluten or not. Healthy volunteers were not able to differentiate the appearance and taste of gluten capsules from those of placebo capsules. Assuming a within-patient comparison and a SD of the overall score of 40, 70 subjects per arm would be needed in order to achieve a power of 80%, at a 2-sided 5% significance level, if the true difference is 15.
- Conditions
- Nonceliac Gluten Sensitivity
- Being tested
- Gluten or placebo capsules
- Keywords
- dose-finding, extraintestinal symptoms, gluten, intestinal symptoms, placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gluten or placebo capsulesDiagnostic test
Administration of gluten or placebo capsules
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Diagnostic Test: Gluten or placebo capsules |
| 1B - NCGS | Active comparator | Seventy subjects with nonceliac gluten sensitivity will be given 10 gastrosoluble capsules containing purified wheat gluten corresponding to a daily gluten intake of 6.0 grams for five days. In order to maintain the double-blind, patients will be also given 4 capsules of placebo (rice starch) per day. 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. Receives: Diagnostic Test: Gluten or placebo capsules |
| 1C - NCGS | Active comparator | Seventy subjects with nonceliac gluten sensitivity will be given 7 gastrosoluble capsules containing purified wheat gluten corresponding to a daily gluten intake of 4.2 grams for five days. In order to maintain the double-blind, patients will be also given 7 capsules of placebo (rice starch) per day. 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. Receives: Diagnostic Test: Gluten or placebo capsules |
| 2C - NCGS | Placebo comparator | Seventy subjects with nonceliac gluten sensitivity will be given 14 daily gastrosoluble capsules containing placebo (rice starch) 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 7 daily gastrosoluble capsules containing purified wheat gluten corresponding to a daily gluten intake of 4.2 grams for five days. In order to maintain the double-blind, patients will be also given 7 capsules of placebo (rice starch) per day. 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. Receives: Diagnostic Test: Gluten or placebo capsules |
| 2B - NCGS | Placebo comparator | Seventy subjects with nonceliac gluten sensitivity will be given 14 daily gastrosoluble capsules containing placebo (rice starch) 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 10 daily gastrosoluble capsules containing purified wheat gluten corresponding to a daily gluten intake of 6.0 grams for five days. In order to maintain the double-blind, patients will be also given 4 capsules of placebo (rice starch) per day. 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. Receives: Diagnostic Test: Gluten or placebo capsules |
| 2A - NCGS | Placebo comparator | Seventy subjects with nonceliac gluten sensitivity will be given 14 daily gastrosoluble capsules containing placebo (rice starch) 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 purified wheat gluten corresponding to a daily gluten intake of 8.4 grams 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. Receives: Diagnostic Test: Gluten or placebo capsules |
| 1A - HV | Active comparator | Seventy healthy volunteers 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. Receives: Diagnostic Test: Gluten or placebo capsules |
| 1B - HV | Active comparator | Seventy healthy volunteers will be given 10 gastrosoluble capsules containing purified wheat gluten corresponding to a daily gluten intake of 6.0 grams for five days. In order to maintain the double-blind, patients will be also given 4 capsules of placebo (rice starch) per day. 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. Receives: Diagnostic Test: Gluten or placebo capsules |
| 1C - HV | Active comparator | Seventy healthy volunteers will be given 7 gastrosoluble capsules containing purified wheat gluten corresponding to a daily gluten intake of 4.2 grams for five days. In order to maintain the double-blind, patients will be also given 7 capsules of placebo (rice starch) per day. 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. Receives: Diagnostic Test: Gluten or placebo capsules |
| 2C- HV | Placebo comparator | Seventy healthy volunteers will be given 14 daily gastrosoluble capsules containing placebo (rice starch) 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 7 daily gastrosoluble capsules containing purified wheat gluten corresponding to a daily gluten intake of 4.2 grams for five days. In order to maintain the double-blind, patients will be also given 7 capsules of placebo (rice starch) per day. 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. Receives: Diagnostic Test: Gluten or placebo capsules |
| 2B - HV | Placebo comparator | Seventy healthy volunteers will be given 14 daily gastrosoluble capsules containing placebo (rice starch) 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 7 daily gastrosoluble capsules containing purified wheat gluten corresponding to a daily gluten intake of 4.2 grams for five days. In order to maintain the double-blind, patients will be also given 7 capsules of placebo (rice starch) per day. 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. Receives: Diagnostic Test: Gluten or placebo capsules |
| 2A - HV | Placebo comparator | Seventy healthy volunteers will be given 14 daily gastrosoluble capsules containing placebo (rice starch) 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 purified wheat gluten corresponding to a daily gluten intake of 8.4 grams 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. Receives: Diagnostic Test: Gluten or placebo capsules |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 18 months
The identification of patients with true nonceliac gluten sensitivity
True nonceliac gluten-sensitive patients will be defined as having at the end of the trial a delta overall score higher than the mean delta overall score plus two standard deviations of healthy volunteers taking the same daily gluten dose.
Measured: 18 months
Laboratory parameters as predictors of true nonceliac gluten sensitivity
To verify whether laboratory parameters (erum IgG AGA, HLA genotyping and intraepithelial lymphocyte density) at baseline might be predictive of true nonceliac gluten sensitivity
Measured: 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
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2017
- Study start13 Jun 2017
- Primary completion13 Jun 2019 (estimated)
- Study completion13 Dec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Nonceliac Gluten SensitivityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Randomized, dose-finding, double-blind, placebo-controlled, crossover gluten challenge trial
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 840 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Antonio Di Sabatino
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Antonio Di Sabatino, Fondazione IRCCS Policlinico San Matteo di Pavia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03188367
- Sponsor's protocol ID
- 20150017440
- Acronym
- RAPLAGE
- Status last verified
- Aug 2018
- First submitted
- 13 Jun 2017
- Last updated
- 10 Aug 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Di Sabatino A, Volta U, Salvatore C, Biancheri P, Caio G, De Giorgio R, Di Stefano M, Corazza GR. Small Amounts of Gluten in Subjects With Suspected Nonceliac Gluten Sensitivity: A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Trial. Clin Gastroenterol Hepatol. 2015 Sep;13(9):1604-12.e3. doi: 10.1016/j.cgh.2015.01.029. Epub 2015 Feb 19.
PubMed 25701700
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Dose-finding, Double-blind, Placebo-controlled, Crossover Gluten Challenge Trial in Subjects With Nonceliac Gluten-sensitivity
- ClinicalTrials.gov ID
- NCT03188367
- Acronym / sponsor ID
- RAPLAGE / 20150017440
- Conditions
- Nonceliac Gluten Sensitivity
- Keywords
- dose-finding, extraintestinal symptoms, gluten, intestinal symptoms, placebo
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 840 participants (estimated)
- Lead sponsor
- Antonio Di SabatinoUniversity, hospital or other
- Study start
- 13 Jun 2017 (actual)
- Primary completion
- 13 Jun 2019 (estimated)
- Study completion
- 13 Dec 2020 (estimated)
- First posted
- 15 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The Investigators will consecutively enroll adult patients referred to outpatients' Clinics of 21 Centres because of persistence of relevant intestinal and extraintestinal symptoms believed by them to be caused by the ingestion of food containing even low doses of gluten. In their clinical management patients in gluten-containing diet since at least two months will undergo ad hoc tests including serum determination of IgA anti-tissue transglutaminase and anti-endomysial antibodies, IgG anti-gliadin antibodies (AGA), total IgA and IgE, wheat-specific IgE, upper endoscopy with collection of multiple duodenal biopsies, HLA genotyping, fecal calprotectin and lactose breath test. The Investigators will investigate serum AGA IgG since they have been detected in some patients with "suspected" nonceliac gluten sensitivity. Patients with celiac disease, wheat allergy, intolerance to further food source of fermentable oligo- and disaccharides, monosaccharides and polyols, lactose intolerance, Helicobacter pylori infection, giardiasis, inflammatory bowel disease, cirrhosis, excessive alcohol intake, intake of nonsteroidal anti-inflammatory agents, use of systemic immunosuppressant medication, poorly controlled psychiatric disease, pregnancy and those unable to give written informed consent will be excluded. The Investigators will also recruit as control group 420 age- and sex-matched healthy volunteers, undergoing IgG AGA and all negative for anti-tissue transglutaminase antibodies. Healthy volunteers will not be affected by any comorbidity and food intolerance.
Each Centre will enroll 20 patients with suspected nonceliac gluten sensitivity and 20 healthy volunteers. Recruitment of patients and, at greater extent, healthy volunteers should not be an issue as the 21 Centres involved in this trial are well-known for diagnosis and treatment of gluten-related disorders. The Investigators will consider drop-outs from the study all the patients who will fail to attend even a single appointment or test in the trial. Moreover, compliance with the study treatment will be assessed by unused capsule counts at T2 and T4. Compliance with the gluten-free diet at each time point will be assessed through a validated questionnaire. To exclude the possibility of patients being able to discriminate between gluten capsules and placebo capsules, we preliminarily tested capsule recognition in a group of 20 healthy volunteers. On two different days, healthy volunteers were asked to take capsules and then clearly state if the capsules contained gluten or not. Healthy volunteers were not able to differentiate the appearance and taste of gluten capsules from those of placebo capsules. Assuming a within-patient comparison and a SD of the overall score of 40, 70 subjects per arm would be needed in order to achieve a power of 80%, at a 2-sided 5% significance level, if the true difference is 15.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 12
- Model description
- Randomized, dose-finding, double-blind, placebo-controlled, crossover gluten challenge trial
| Arm | Type | Receives |
|---|---|---|
| 1A - NCGS | Active comparator | Diagnostic Test: Gluten or placebo capsulesSeventy 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. |
| 1B - NCGS | Active comparator | Diagnostic Test: Gluten or placebo capsulesSeventy subjects with nonceliac gluten sensitivity will be given 10 gastrosoluble capsules containing purified wheat gluten corresponding to a daily gluten intake of 6.0 grams for five days. In order to maintain the double-blind, patients will be also given 4 capsules of placebo (rice starch) per day. 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. |
| 1C - NCGS | Active comparator | Diagnostic Test: Gluten or placebo capsulesSeventy subjects with nonceliac gluten sensitivity will be given 7 gastrosoluble capsules containing purified wheat gluten corresponding to a daily gluten intake of 4.2 grams for five days. In order to maintain the double-blind, patients will be also given 7 capsules of placebo (rice starch) per day. 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. |
| 2C - NCGS | Placebo comparator | Diagnostic Test: Gluten or placebo capsulesSeventy subjects with nonceliac gluten sensitivity will be given 14 daily gastrosoluble capsules containing placebo (rice starch) 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 7 daily gastrosoluble capsules containing purified wheat gluten corresponding to a daily gluten intake of 4.2 grams for five days. In order to maintain the double-blind, patients will be also given 7 capsules of placebo (rice starch) per day. 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. |
| 2B - NCGS | Placebo comparator | Diagnostic Test: Gluten or placebo capsulesSeventy subjects with nonceliac gluten sensitivity will be given 14 daily gastrosoluble capsules containing placebo (rice starch) 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 10 daily gastrosoluble capsules containing purified wheat gluten corresponding to a daily gluten intake of 6.0 grams for five days. In order to maintain the double-blind, patients will be also given 4 capsules of placebo (rice starch) per day. 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. |
| 2A - NCGS | Placebo comparator | Diagnostic Test: Gluten or placebo capsulesSeventy subjects with nonceliac gluten sensitivity will be given 14 daily gastrosoluble capsules containing placebo (rice starch) 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 purified wheat gluten corresponding to a daily gluten intake of 8.4 grams 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. |
| 1A - HV | Active comparator | Diagnostic Test: Gluten or placebo capsulesSeventy healthy volunteers 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. |
| 1B - HV | Active comparator | Diagnostic Test: Gluten or placebo capsulesSeventy healthy volunteers will be given 10 gastrosoluble capsules containing purified wheat gluten corresponding to a daily gluten intake of 6.0 grams for five days. In order to maintain the double-blind, patients will be also given 4 capsules of placebo (rice starch) per day. 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. |
| 1C - HV | Active comparator | Diagnostic Test: Gluten or placebo capsulesSeventy healthy volunteers will be given 7 gastrosoluble capsules containing purified wheat gluten corresponding to a daily gluten intake of 4.2 grams for five days. In order to maintain the double-blind, patients will be also given 7 capsules of placebo (rice starch) per day. 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. |
| 2C- HV | Placebo comparator | Diagnostic Test: Gluten or placebo capsulesSeventy healthy volunteers will be given 14 daily gastrosoluble capsules containing placebo (rice starch) 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 7 daily gastrosoluble capsules containing purified wheat gluten corresponding to a daily gluten intake of 4.2 grams for five days. In order to maintain the double-blind, patients will be also given 7 capsules of placebo (rice starch) per day. 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. |
| 2B - HV | Placebo comparator | Diagnostic Test: Gluten or placebo capsulesSeventy healthy volunteers will be given 14 daily gastrosoluble capsules containing placebo (rice starch) 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 7 daily gastrosoluble capsules containing purified wheat gluten corresponding to a daily gluten intake of 4.2 grams for five days. In order to maintain the double-blind, patients will be also given 7 capsules of placebo (rice starch) per day. 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. |
| 2A - HV | Placebo comparator | Diagnostic Test: Gluten or placebo capsulesSeventy healthy volunteers will be given 14 daily gastrosoluble capsules containing placebo (rice starch) 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 purified wheat gluten corresponding to a daily gluten intake of 8.4 grams 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- persistence of relevant intestinal and extraintestinal symptoms believed by them to be caused by the ingestion of food containing even low doses of gluten
Key exclusion criteria (14 listed)
- celiac disease
- wheat allergy
- intolerance to further food source of fermentable oligo- and disaccharides, monosaccharides and polyols
- lactose intolerance
- Helicobacter pylori infection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Gluten or placebo capsulesAdministration of gluten or placebo capsules | Diagnostic test | 1A - HV, 1A - NCGS, 1B - HV, 1B - NCGS, 1C - HV, 1C - NCGS, 2A - HV, 2A - NCGS, 2B - HV, 2B - NCGS, 2C - NCGS, 2C- HV |
Primary outcome
Change in delta overall (intestinal plus extraintestinal) score in nonceliac gluten sensitivity
Time frame: 18 months
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.
4 secondary outcomes
The change in individual symptom scores between the 5-day treatment with gluten and the 5-day treatment with placebo
Time frame: 18 months
The identification of patients with true nonceliac gluten sensitivity
Time frame: 18 months
Laboratory parameters as predictors of true nonceliac gluten sensitivity
Time frame: 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
Time frame: 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2018.
- Background: PubMed 25701700Di Sabatino A, Volta U, Salvatore C, Biancheri P, Caio G, De Giorgio R, Di Stefano M, Corazza GR. Small Amounts of Gluten in Subjects With Suspected Nonceliac Gluten Sensitivity: A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Trial. Clin Gastroenterol Hepatol. 2015 Sep;13(9):1604-12.e3. doi: 10.1016/j.cgh.2015.01.029. Epub 2015 Feb 19.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study of Nonceliac Gluten Sensitivity, run by Antonio Di Sabatino at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Antonio Di Sabatino, MD (+39 0382 501596, a.disabatino@smatteo.pv.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in delta overall (intestinal plus extraintestinal) score in nonceliac gluten sensitivity (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03188367, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Aug 2018.