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

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

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.

Study Overview

• Status: Completed
• Conditions: Celiac Disease
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Aspergillus niger prolyl endoprotease

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.

• Study Type: Interventional
• Enrollment (Anticipated): 14
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • VU University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Amsterdam UMC, location VUmc
• Collaborators: Leiden University Medical Center; DSM Food Specialties
• Investigators: Principal Investigator: Greetje J Tack, MD, Amsterdam UMC, location VUmc

Publications and helpful links

General Publications

• Tack GJ, van de Water JM, Bruins MJ, Kooy-Winkelaar EM, van Bergen J, Bonnet P, Vreugdenhil AC, Korponay-Szabo I, Edens L, von Blomberg BM, Schreurs MW, Mulder CJ, Koning F. Consumption of gluten with gluten-degrading enzyme by celiac patients: a pilot-study. World J Gastroenterol. 2013 Sep 21;19(35):5837-47. doi: 10.3748/wjg.v19.i35.5837.

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (Actual): May 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: December 17, 2008
• First Submitted That Met QC Criteria: December 17, 2008
• First Posted (Estimate): December 18, 2008

Study Record Updates

• Last Update Posted (Estimate): January 19, 2011
• Last Update Submitted That Met QC Criteria: January 18, 2011
• Last Verified: May 1, 2009

More Information

Terms related to this study

• Keywords: treatment; Celiac disease; gluten; Coeliac disease; AN-PEP; prolyl endoprotease
• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Gastrointestinal Diseases; Intestinal Diseases; Malabsorption Syndromes; Celiac Disease
• Other Study ID Numbers: RD.0601.54; NTR1281