Effect of Aspergillus Niger Prolyl Endoprotease (AN-PEP) Enzyme on the Effects of Gluten Ingestion in Patients With Coeliac Disease
Primary Purpose
Celiac Disease
Status
Completed
Phase
Phase 1
Locations
Netherlands
Study Type
Interventional
Intervention
Aspergillus niger prolyl endoprotease
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Celiac Disease focused on measuring Celiac disease, Coeliac disease, treatment, AN-PEP, prolyl endoprotease, gluten
Eligibility 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.
Sites / Locations
- VU University Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
ANPEP
Placebo
Arm Description
Aspergillus niger prolyl endoprotease (AN-PEP), a microbial-derived prolyl endoprotease which cleaves gluten
Outcomes
Primary Outcome Measures
Histopathological changes according to the Modified Marsh criteria
The presence of coeliac disease specific antibodies (EMA, tTGA, gliadin)
Secondary Outcome Measures
Presence and activity of gluten reactive Tcells isolated from biopsies and serum
Immunophenotype of lymphocytes isolated from biopsies
Clinical symptoms after gluten intake with and without AN-PEP
Full Information
NCT ID
NCT00810654
First Posted
December 17, 2008
Last Updated
January 18, 2011
Sponsor
Amsterdam UMC, location VUmc
Collaborators
DSM Food Specialties, Leiden University Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT00810654
Brief Title
Effect of Aspergillus Niger Prolyl Endoprotease (AN-PEP) Enzyme on the Effects of Gluten Ingestion in Patients With Coeliac Disease
Official Title
Study on The Effectiveness of Oral Administration of Prolyl Endoprotease for Gluten Detoxification as a Means to Treat Coeliac Disease
Study Type
Interventional
2. Study Status
Record Verification Date
May 2009
Overall Recruitment Status
Completed
Study Start Date
May 2008 (undefined)
Primary Completion Date
May 2009 (Actual)
Study Completion Date
December 2009 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Amsterdam UMC, location VUmc
Collaborators
DSM Food Specialties, Leiden University Medical Center
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Celiac Disease
Keywords
Celiac disease, Coeliac disease, treatment, AN-PEP, prolyl endoprotease, gluten
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
14 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
ANPEP
Arm Type
Experimental
Arm Description
Aspergillus niger prolyl endoprotease (AN-PEP), a microbial-derived prolyl endoprotease which cleaves gluten
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Dietary Supplement
Intervention Name(s)
Aspergillus niger prolyl endoprotease
Other Intervention Name(s)
AN-PEP
Intervention Description
160 PPU daily for 2 weeks
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Histopathological changes according to the Modified Marsh criteria
Time Frame
One week before start, and 2 and 6 weeks after start
Title
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 Measure Information:
Title
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
Title
Immunophenotype of lymphocytes isolated from biopsies
Time Frame
One week before start, and 2 and 6 weeks after start
Title
Clinical symptoms after gluten intake with and without AN-PEP
Time Frame
One week before start, and 2 and 6 weeks after start
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Greetje J Tack, MD
Organizational Affiliation
Amsterdam UMC, location VUmc
Official's Role
Principal Investigator
Facility Information:
Facility Name
VU University Medical Center
City
Amsterdam
ZIP/Postal Code
1081 HV
Country
Netherlands
12. IPD Sharing Statement
Citations:
PubMed Identifier
24124328
Citation
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.
Results Reference
derived
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Effect of Aspergillus Niger Prolyl Endoprotease (AN-PEP) Enzyme on the Effects of Gluten Ingestion in Patients With Coeliac Disease
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