Celiac Disease
Conditions
Keywords
Celiac disease, Coeliac disease, treatment, AN-PEP, prolyl endoprotease, gluten
Brief summary
Oral supplementation with enzymes that can cut gluten has been suggested as a potential treatment modality for coeliac disease. In the present study the investigators wish to determine if co-administration of such an enzyme, a prolyl endoprotease derived from the food grade organism Aspergillis niger (AN-PEP), is capable of detoxifying 8 grams of gluten in a commercial food product.
Detailed description
The objective of the study is to determine whether AN-PEP enzyme is effective in mitigating the effects of 8 g wheat protein ingestion in patients with celiac disease. Fourteen patients with coeliac disease, 18-70 years old are recruited. During the first period, patients consume once daily a gluten-containing food product with the AN-PEP enzyme for 2 weeks. After a 2-week washout period (second period), patients enter the third period of this study, and are randomized to one of two groups and consume the same gluten-containing food product with AN-PEP or placebo. Period 1: Patients are given a food product containing 8 g of wheat protein, to which AN-PEP is added, once daily for 14 d. Period 2: Wash-out period of 14 d. During this period, patients will consume a gluten-free diet. Period 3: Patients who are negative for coeliac disease symptoms during the 1st period will be randomized across two groups. Both groups receive a food product containing 8 g of wheat protein once daily for 14 d. One group receives additional AN-PEP with the gluten meal whereas the other group receives the placebo. Patients will visit the outpatient clinic five times; one visit before the start of the study, a visit during and at the end of the first period, and a visit during and at the end of the third period. During three of the visits, spike-biopsies are taken from the duodenum by oesophago-gastro-duodenoscopy. Blood samples are taken during all of the five visits. Patients will also fill in a quality of life questionnaire at the start and the end of the first and third period.
Interventions
DIETARY_SUPPLEMENTAspergillus niger prolyl endoprotease
160 PPU daily for 2 weeks
DIETARY_SUPPLEMENTPlacebo
Placebo
Sponsors
DSM Food Specialties
Leiden University Medical Center
Amsterdam UMC, location VUmc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of coeliac disease (Marsh III B/C) ; that means crypt hyperplasia and subtotal or total villous atrophy, while using a normal diet followed by normalisation and clinical improvement on a gluten-free diet; * Detectable coeliac disease specific antibodies (EMA, tTGA) at time of diagnosis. * A strict gluten free diet for at least 1 year and normalised villous architecture (Marsh 0/I); * Male and female, 18-70 years old; * No detectable anti-endomysium and low anti-tissue transglutaminase (\< 4 U/ml) prior to the start of the study; * Patient is willing to undergo all protocol related assessments and visits (including up to 3 separate oesophago-gastro-duodenoscopies with multiple biopsies taken each time from the descending duodenum); * Patient has read the information provided on the study and given written consent; * Female participants at fertile age must use adequate contraception.
Exclusion criteria
* Use of any immunoregulatory drug within the last 6 months; * Use of any anticoagulant drug; * Clinically suspected bleeding tendency; * Pregnancy or breast feeding; * Presence of any concurrent active infection; * IgA deficiency.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Histopathological changes according to the Modified Marsh criteria | One week before start, and 2 and 6 weeks after start |
| The presence of coeliac disease specific antibodies (EMA, tTGA, gliadin) | One week before start, and 2 and 6 weeks after start |
Secondary
| Measure | Time frame |
|---|---|
| Presence and activity of gluten reactive Tcells isolated from biopsies and serum | One week before start, and 2 and 6 weeks after start |
| Immunophenotype of lymphocytes isolated from biopsies | One week before start, and 2 and 6 weeks after start |
| Clinical symptoms after gluten intake with and without AN-PEP | One week before start, and 2 and 6 weeks after start |
Countries
Netherlands
Outcome results
None listed