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

This study has been completed.
Sponsor:
Collaborators:
DSM Food Specialties
Leiden University Medical Center
Information provided by:
VU University Medical Center
ClinicalTrials.gov Identifier:
NCT00810654
First received: December 17, 2008
Last updated: January 18, 2011
Last verified: May 2009
History of Changes
  Purpose

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 Intervention Phase
Celiac Disease
 Dietary Supplement: Aspergillus niger prolyl endoprotease
Dietary Supplement: Placebo
 Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:

MedlinePlus related topics: Celiac Disease
U.S. FDA Resources

Further study details as provided by VU University Medical Center:

Primary Outcome Measures:
  • Histopathological changes according to the Modified Marsh criteria [ Time Frame: One week before start, and 2 and 6 weeks after start ] [ Designated as safety issue: No ]
  • The presence of coeliac disease specific antibodies (EMA, tTGA, gliadin) [ Time Frame: One week before start, and 2 and 6 weeks after start ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Immunophenotype of lymphocytes isolated from biopsies [ Time Frame: One week before start, and 2 and 6 weeks after start ] [ Designated as safety issue: No ]
  • Clinical symptoms after gluten intake with and without AN-PEP [ Time Frame: One week before start, and 2 and 6 weeks after start ] [ Designated as safety issue: No ]

Estimated Enrollment: 14
Study Start Date: May 2008
Study Completion Date: December 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00810654

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

No publications provided

Responsible Party: C.J.Mulder, VU University Medical Center
ClinicalTrials.gov Identifier: NCT00810654     History of Changes
Other Study ID Numbers: RD.0601.54, NTR1281
Study First Received: December 17, 2008
Last Updated: January 18, 2011
Health Authority: Netherlands: Independent Ethics Committee

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

ClinicalTrials.gov processed this record on May 22, 2013