Oral challenge test with gluten versus placebo to identify patients with nonceliac gluten sensitivity (NCGS)
| ISRCTN | ISRCTN72857280 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN72857280 |
| Secondary identifying numbers | 20120011203 |
- Submission date
- 28/06/2014
- Registration date
- 31/07/2014
- Last edited
- 24/02/2015
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Digestive System
Plain English summary of protocol
Background and study aims
Non-celiac gluten sensitivity (NCGS) is a condition with symptoms similar to that of celiac disease. These include depression, abdominal pain, bloating, diarrhoea, constipation, fatigue, joint pain and a foggy mind. However, despite the number of symptoms common to both conditions, people with NCGS do not test positive for celiac disease or a wheat allergy. Indeed, there is a debate on whether the disease exists at all. The aim of this study is to test the effect of low amounts (doses) of gluten in patients suspected of having NCGS.
Who can participate?
Adult patients with persistent NCGS symptoms and having eaten a diet containing gluten for at least the last two months.
What does the study involve?
Participants are randomly assigned to one of two groups. Those in group 1 are given a pill containing 4.375 grams of gluten for a week. Those in group 2 are given a dummy (placebo) pill made out of rice starch. Then, after a one week wash-out period (where no treatment is given to either group), the groups cross over with Group 1 taking the placebo and group 2 taking the gluten containing pill for a week. The effects of taking the gluten compared with the placebo are then analysed.
What are the possible benefits and risks of participating?
There are no risks associated with taking part in the trial as participants are not taking drugs but common components of a normal diet. Benefits associated with taking part in our trial might be the diagnosis of true NCGS.
Where is the study run from?
St. Matteo Hospital (Italy)
When is the study starting and how long is it expected to run for?
October 2012 to January 2014
Who is funding the study?
St. Matteo Hospital (Italy)
Who is the main contact?
Dr Antonio Sabatino
a.disabatino@smatteo.pv.it
Contact information
Scientific
First Department of Medicine
St Matteo Hospital Foundation
Piazzale Golgi 19
Pavia
27100
Italy
Study information
| Study design | Randomized double-blind placebo-controlled cross-over trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised cross over trial |
| Study setting(s) | Hospital |
| Study type | Diagnostic |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | Effect of low gluten doses in patients suspected of having nonceliac gluten sensitivity (NCGS): a randomized, double-blind, placebo-controlled cross-over gluten challenge trial |
| Study acronym | NCGS |
| Study objectives | We hypothesized that even low gluten doses could worsen overall (intestinal and extraintestinal) symptoms in patients strongly suspected of having NCGS |
| Ethics approval(s) | Ethics Committee of the St. Matteo Hospital Foundation - Pavia (Italy), 19/10/2012, ref. 4468/2012 |
| Health condition(s) or problem(s) studied | Nonceliac gluten sensivity |
| Intervention | Patients will be asked to fill in a daily questionnaire in order to assess a rating scale of both intestinal and extraintestinal symptoms over a 5-week period. Participants will be asked to follow a strict gluten-free diet (GFD) starting one week before the randomization and continuing until the end of the study period. After the first week of GFD, patients will be given either gastrosoluble capsules containing purified wheat gluten (10 capsules ingested in no more than two times over the day, corresponding to a daily gluten intake of 4.375 grams, equivalent to about 2 slices of white bread) or gastrosoluble capsules containing rice starch (10 capsules ingested in no more than two times over the day, corresponding to a daily rice starch intake of 4.375 grams) as placebo for one week. At the end of the first treatment week, patients from both arms will continue only their wash-out from gluten, without taking a capsule. Subsequently, individuals belonging to the first arm will be given placebo capsules, while individuals belonging to the second arm will be given gluten capsules. After the second treatment week, all patients will continue with their wash-out from dietary gluten. During the trial, patients will undergo five outpatient weekly appointments, during which patients will provide their filled questionnaires and investigators will count any unused capsules remaining in capsule dispensers. |
| Intervention type | Other |
| Primary outcome measure | The primary outcome is the change in the weekly overall symptom score, as assessed by the sum of intestinal and extraintestinal scores, between the 1-week treatment with gluten and the 1-week treatment with placebo. The 15 intestinal symptoms, which patients will be asked to grade daily from 0 to 3 (0=absent; 1=mild; 2=relevant, 3=severe and interfering with daily activities) are: 1. Abdominal pain 2. Abdominal bloating 3. Wind 4. Diarrhea 5. Borborygmus 6. Reduced consistency of stools 7. Increased consistency of stools 8. Constipation 9. Urgency 10. Incomplete evacuation 11. Nausea 12. Heartburn 13. Belching 14. Acid regurgitation 15. Epigastric pain. The 13 extraintestinal symptoms, which patients will be asked to grade daily from 0 (absent) to 1 (present), are: 1. Tiredness 2. Malaise 3. Headache 4. Depression 5. Anxiety 6. Foggy mind 7. Aphthous stomatitis 8. Paresthesia 9. Arthralgia 10. Myalgia 11. Asthma 12. Rhinitis 13. Skin rash |
| Secondary outcome measures | Secondary outcomes are: 1. The change in individual symptom scores between the 1-week treatment with gluten and the 1-week treatment with placebo 2. The identification of patients with true NCGS 3. To verify whether laboratory parameters at baseline are predictive of true NCGS. True NCGS patients are defined as having at the end of the trial a delta overall score - calculated by subtracting the weekly overall score under placebo from the weekly overall score under gluten- higher than the mean delta overall score plus two standard deviations. Laboratory predictors include serum IgG AGA, fecal calprotectin, HLA genotyping and intraepithelial lymphocyte density. |
| Overall study start date | 20/10/2012 |
| Completion date | 31/01/2014 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | Al least 58 randomized participants |
| Key inclusion criteria | 1. Adult patients referred to our outpatients' clinics 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. 2. Under gluten-containing diet at the time of screening since at least two months 3. Happy to undergo ad hoc screening, including: 3.a. Serum determination of IgA anti-transglutaminase and anti-endomysial antibodies 3.b. IgG anti-gliadin antibodies (AGA) 3.c. Total IgA and IgE 3.d. Wheat-specific IgE 3.e. Upper endoscopy with collection of multiple duodenal biopsies 3.f. HLA genotyping 3.g. Fecal calprotectin 3.h. Lactose breath test |
| Key exclusion criteria | 1. Other significant gastrointestinal diseases, such as inflammatory bowel disease or cirrhosis, 2. Other clinically significant comorbidities such as diabetes, use of nonsteroidal anti-inflammatory agents or systemic immunomodulators 3. Pregnancy 4. Inability to give written informed consent 5. Reported psychiatric disorder 6. Excessive alcohol intake Only patients, who at the end of the screening are found not to be affected by celiac disease, wheat allergy, lactose or FODMAP intolerance, Helicobacter pylori infection, giardiasis, and who complain of relevant gluten-dependent symptoms that is affecting the overall quality of life, will be randomized according to a computer-generated list of random numbers held by an independent observer to either the gluten or the placebo treatment group. |
| Date of first enrolment | 20/10/2012 |
| Date of final enrolment | 31/01/2014 |
Locations
Countries of recruitment
- Italy
Study participating centre
27100
Italy
Sponsor information
Hospital/treatment centre
Piazzale Golgi 5
Pavia
27100
Italy
"ROR" |
https://ror.org/05w1q1c88 |
|---|
Funders
Funder type
Hospital/treatment centre
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/09/2015 | Yes | No |
