None listed
Conditions
Brief summary
People with coeliac disease have an acquired immune reaction that can cause acute symptoms similar to food poisoning within two hours of eating gluten. This study aims to define the minimum amount of gluten that activates the immune response to gluten, injures the gut and causes symptoms in patients with coeliac disease. This will be achieved by assessing symptoms and measuring a specific type of molecule (biomarker) in the blood and tissue called interleukin 2 (IL-2) after participants consume a defined dose of gluten. Study findings may be used to inform food safety standards for people with coeliac disease and will advance knowledge and understanding of the clinical effects of gluten in people with coeliac disease.
Interventions
In this study, participants will be required to ingest a gelatin capsule by mouth containing a randomly allocated dose of gluten or placebo (no gluten) as part of three separate gluten challenges. Either one or two gelatin capsules will be administered with the dose evenly distributed to achieve the specific dose. All doses will be administered to participants under direct supervision of study staff.
This research study will enroll participants into four different groups. Participants will be
In this study, participants will be required to ingest a gelatin capsule by mouth containing a randomly allocated dose of gluten or placebo (no gluten) as part of three separate gluten challenges. Either one or two gelatin capsules will be administered with the dose evenly distributed to achieve the specific dose. All doses will be administered to participants under direct supervision of study staff. This research study will enroll participants into four different groups. Participants will be recruited and studied in sequential cohorts. Each Cohort will complete screening and intervention before participants in the subsequent cohorts are enrolled. Unblinded data from each completed cohort will be analysed to determine dose levels of gluten for the subsequent cohort. - Group 1: 6 participants will undergo 3 gluten challenges requiring ingestion of 1g gluten (approximately half a slice of bread) at each challenge. Challenges will take place one month apart. This will be assessed first in 3 unmasked challenges at one-month intervals and is likely to provide a positive control” for IL-2 release. Analysis of serum IL-2 data from Cohort 1 will determine (1) the optimal assessment of serum IL-2 (either at baseline and one-time point after gluten, or serum pooled from collections at 2, 4, and 6 h), and (2) validate that a one-month interval between gluten challenges does not significantly alter IL-2 response strength. - Group 2: 15 participants will undergo 3 gluten challenges requiring ingestion of either 0mg, 13mg, 90mg, or 610mg of gluten (approximately one-third of a slice of bread) at each challenge. Participants will be randomized to receive any of these doses (13mg, 90mg or 130mg or placebo 0mg. Challenges will take place one month apart. - Groups 3 and 4: 15 participants in each cohort will undergo 3 gluten challenges requiring ingestion of up to 610mg of gluten (approximately one-third of a slice of bread) at each challenge. Altogether 12 patients will receive the high, medium, and low doses in one of their 3 food challenges, and 9 patients will receive a placebo (empty gelatin capsule) on one occasion in any order. The doses of gluten used in groups 3 and 4 are determined by the lowest dose of gluten to elicit an immune response in the previous group. Challenges will take place one month apart. Serum IL-2 responses to placebo will establish a cutoff level for the upper level of a negative response (for example mean + 3 standard deviation or a 95% confidence interval). Participants who are randomly allocated to consume a dose of gluten in the gluten challenge will ingest gelatin capsules comprising vital wheat gluten and micro cellulose filler. Capsules will be administered under the direct supervision of study site staff. After ingesting the capsule, the participant will be observed for 6 hours and monitored for side effects. During the 6 hour observation period, participants will have blood collected at two-hourly intervals to measure immune response and will complete symptom questionnaires hourly. Urine will be collected to measure gluten molecules in the urine. The gluten challenges will be administered by registered nurses and overseen by a medical doctor. Participants will be required to attend Wesley Medical Research in person for the 3 separate gluten challenges, in addition to a screening visit (to determine if the participant is suitable for the study) and an end of study visit. Gluten challenges will either be administered individually or with other participants. The total duration of participation in the study is between 12 and 18 weeks.
Sponsors
Wesley Medical Research
Study design
Allocation
Randomised controlled trial
Intervention model
Other
Primary purpose
Diagnosis
Masking
Blinded (masking used) (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
25 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Adults 25 to 75 years of age (inclusive) who have signed an informed consent form. 2. A history of Coeliac disease diagnosed on the basis of duodenal biopsy showing villous atrophy and abnormal coeliac disease-specific serology (anti-transglutaminase 2 IgA, deamidated gliadin peptide IgG, or anti-endomysial IgA. 3. Initiated gluten-free diet at least 2 years prior to screening. 4. No known gluten exposure within the previous one month at screening 5. No known allergy to gluten. 6. Willingness to consume up to 1 g of gluten (equivalent to about 1/2 slice of standard bread) at one time. 7. Willingness to undergo study procedures. 8. Able to read and understand English.
Exclusion criteria
1. Symptoms of fever, cough, shortness of breath, or suspicion of COVID-19 infection. 2. Known consumption of gluten-containing food within the previous one month. 3. Any medical condition or an immune-suppressing medical treatment taken within the previous 3 months that in the opinion of the investigator would impact the immune response (other than coeliac disease), confound interpretation of study results, or pose an increased risk to the patient. Topical or inhaled corticosteroids are acceptable. 4. Females who are pregnant, including those with positive urinary pregnancy test on the first day of screening. 5. Positive at Screening for both TGA and DGP-G serology tests, but note that elevation of one serology test is not an exclusion.
Outcome results
None listed