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
  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:


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
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, see Learn About Clinical Studies.

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 by VU University Medical Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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 September 29, 2014