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

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Celiac Disease	Dietary Supplement: Aspergillus niger prolyl endoprotease; Dietary Supplement: Placebo	Phase 1; Phase 2

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 Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	14 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Study on The Effectiveness of Oral Administration of Prolyl Endoprotease for Gluten Detoxification as a Means to Treat Coeliac Disease
Study Start Date :	May 2008
Actual Primary Completion Date :	May 2009
Actual Study Completion Date :	December 2009

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
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 Name: AN-PEP
Placebo Comparator: Placebo	Dietary Supplement: Placebo; Placebo

Outcome Measures

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Primary Outcome Measures :

1. Histopathological changes according to the Modified Marsh criteria [ Time Frame: One week before start, and 2 and 6 weeks after start ]
2. The presence of coeliac disease specific antibodies (EMA, tTGA, gliadin) [ Time Frame: One week before start, and 2 and 6 weeks after start ]

Secondary Outcome Measures :

1. Presence and activity of gluten reactive Tcells isolated from biopsies and serum [ Time Frame: One week before start, and 2 and 6 weeks after start ]
2. Immunophenotype of lymphocytes isolated from biopsies [ Time Frame: One week before start, and 2 and 6 weeks after start ]
3. Clinical symptoms after gluten intake with and without AN-PEP [ Time Frame: One week before start, and 2 and 6 weeks after start ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 70 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

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Locations

Netherlands
VU University Medical Center
Amsterdam, Netherlands, 1081 HV

Sponsors and Collaborators

VU University Medical Center

DSM Food Specialties

Leiden University Medical Center

Investigators

Principal Investigator:	Greetje J Tack, MD	VU University Medical Center

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Responsible Party:	C.J.Mulder, VU University Medical Center
ClinicalTrials.gov Identifier:	NCT00810654 History of Changes
Other Study ID Numbers:	RD.0601.54; NTR1281
First Posted:	December 18, 2008
Last Update Posted:	January 19, 2011
Last Verified:	May 2009

Keywords provided by VU University Medical Center:

Celiac disease; Coeliac disease; treatment	AN-PEP; prolyl endoprotease; gluten

Additional relevant MeSH terms:

Celiac Disease; Malabsorption Syndromes; Intestinal Diseases	Gastrointestinal Diseases; Digestive System Diseases; Metabolic Diseases