Oral challenge test with gluten versus placebo to identify patients with nonceliac gluten sensitivity (NCGS)

• Register: ISRCTN
• Last refreshed on: 13 January 2015
• Main ID: ISRCTN72857280
• Date of registration: 31/07/2014
• Prospective Registration: No
• Primary sponsor: St. Matteo Hospital Foundation (Italy)
• Public title: Oral challenge test with gluten versus placebo to identify patients with nonceliac gluten sensitivity (NCGS)
• 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
• Date of first enrolment: 20/10/2012
• Target sample size: 58
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN72857280
• Study type: Interventional
• Study design: Randomized, double-blind, placebo-controlled, cross-over trial (Screening)

Countries of recruitment

Italy

Contacts

• Name: Gino Roberto Corazza

Key inclusion & exclusion criteria

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
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.

Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Nonceliac gluten sensivity
Digestive System

Intervention(s)

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.

Primary Outcome(s)

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(s)

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.

Secondary ID(s)

20120011203

Source(s) of Monetary Support

St. Matteo Hospital Foundation, Pavia (Italy)