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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00810654
Recruitment Status : Completed
First Posted : December 18, 2008
Last Update Posted : January 19, 2011
DSM Food Specialties
Leiden University Medical Center
Information provided by:
VU University Medical Center

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.

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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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Celiac Disease

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

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 ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00810654

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VU University Medical Center
Amsterdam, Netherlands, 1081 HV
Sponsors and Collaborators
VU University Medical Center
DSM Food Specialties
Leiden University Medical Center
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Principal Investigator: Greetje J Tack, MD VU University Medical Center
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: C.J.Mulder, VU University Medical Center Identifier: NCT00810654    
Other Study ID Numbers: RD.0601.54
First Posted: December 18, 2008    Key Record Dates
Last Update Posted: January 19, 2011
Last Verified: May 2009
Keywords provided by VU University Medical Center:
Celiac disease
Coeliac disease
prolyl endoprotease
Additional relevant MeSH terms:
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Celiac Disease
Malabsorption Syndromes
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Metabolic Diseases