Effect of Aspergillus Niger Prolyl Endoprotease (AN-PEP) Enzyme on the Effects of Gluten Ingestion in Patients With Coeliac Disease

Study Overview
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Brief Summary
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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
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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.

Official Title
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Study on The Effectiveness of Oral Administration of Prolyl Endoprotease for Gluten Detoxification as a Means to Treat Coeliac Disease

Conditions
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Celiac Disease

Intervention / Treatment
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* Dietary Supplement: Aspergillus niger prolyl endoprotease
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ANPEP<br>Aspergillus niger prolyl endoprotease (AN-PEP), a microbial-derived prolyl endoprotease which cleaves gluten | Dietary Supplement: Aspergillus niger prolyl endoprotease<br>* 160 PPU daily for 2 weeks<br>* Other names: AN-PEP;|
| Placebo Comparator: Placebo<br> | Dietary Supplement: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Celiac disease, Coeliac disease, treatment, AN-PEP, prolyl endoprotease, gluten