Celiac Disease
Conditions
Keywords
Immunotherapy, Gluten challenge, Teriflunomide
Brief summary
The investigators will see if the drug teriflunomide (which is in use in other immune disorder (multiple sclerosis)) can inhibit the immune activation in celiac disease patients during a 3 day gluten challenge. This will be measured in a blood sample.
Detailed description
This is a controlled, double-blind, randomised, singlecentre, placebo-controlled, phase IIa proof-of-concept study on effects of the drug on activation and efflux of gluten specific T cells using HLA-DQ:gluten tetramers. The study will be conducted with two treatment groups in the form of a 2:1 parallel group comparison and will serve to compare oral treatment with 14 mg/d teriflunomide vs. placebo in subjects with well-controlled coeliac disease undergoing gluten challenge. The screening period will be up to 8 weeks, followed by a 7-day run-in treatment period with a loading dose of teriflunomide followed by a 6 day therapeutic maintenance dose, an initial 4-week treatment-free follow-up period and a 6 month closing follow-up.
Interventions
DRUGTeriflunomide Oral Tablet
The study will be conducted with two treatment groups in the form of a 2:1 parallel group comparison and will serve to compare oral treatment with 14 mg/d teriflunomide vs. placebo in subjects with well-controlled coeliac disease undergoing gluten challenge. The screening period will be up to 8 weeks, followed by a 7-day run-in treatment period with a loading dose of teriflunomide followed by a 6 day therapeutic maintenance dose, an initial 4-week treatment-free follow-up period and a 6 month closing follow-up.
Sponsors
Oslo University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Patient aged 18-80 * Willingness to comply with the study procedures and having signed informed, written consent * Previous diagnosis of coeliac disease according to established guidelines based on positive serology (Endomysium test, IgA-TG2 and/or IgGDGP) and a duodenal biopsy showing villous atrophy graded as Marsh 3 * Positive gene test for HLA-DQ2.5 * Adherence to gluten-free diet
Exclusion criteria
* Known intolerance to ingredients of teriflunomide or placebo tablets * Known intolerance to gluten challenge * Known intolerance to cholestyramine * Duration of gluten free diet shorter than six months * Positive serology (IgA-TG2 below upper level of normal) at screening visit * Pregnancy or breast-feeding * Not willing to comply with proper pregnancy control (in females) * Concomitant medication that interferes with immune activation (e.g. steroids, calcineurin inhibitors, biological treatment for inflammatory bowel disease or other immune disorders, further list is given below) * Any other medical condition that in the opinion of the principal investigator makes the individual unsuitable for participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adaptive T cell activation | Blood sample on the 4th day after a 3 day gluten challenge | Expression of CD38 on HLA-DQ:gluten tetramer positive T cells |
Countries
Norway
Outcome results
None listed