effect of aspergillus niger prolyl endoprotease (an-pep) enzyme on the effects of gluten ingestion in patients with coeliac disease

Conditions: Celiac Disease

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.

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.

Eligibility criteria:
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.

Keywords: celiac disease coeliac disease treatment an-pep prolyl endoprotease gluten