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

December 17, 2008
January 18, 2011
May 2008
May 2009   (final data collection date for primary outcome measure)
  • 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 ]
  • Histopathological changes according to the Modified Marsh criteria [ Time Frame: At start, after 3 and after 7 weeks ] [ Designated as safety issue: No ]
  • The presence of coeliac disease specific antibodies (EMA, tTGA, gliadin) [ Time Frame: At start, after 3 and after 7 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00810654 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Presence and activity of gluten reactive Tcells isolated from biopsies and serum [ Time Frame: At start, after 3 and 7 weeks ] [ Designated as safety issue: No ]
  • Immunophenotype of lymphocytes isolated from biopsies [ Time Frame: At start, after 3 and 7 weeks ] [ Designated as safety issue: No ]
  • Clinical symptoms after gluten intake with and without AN-PEP [ Time Frame: At start, after 3 and 7 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Effect of Aspergillus Niger Prolyl Endoprotease (AN-PEP) Enzyme on the Effects of Gluten Ingestion in Patients With Coeliac Disease
Study on The Effectiveness of Oral Administration of Prolyl Endoprotease for Gluten Detoxification as a Means to Treat Coeliac Disease

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.

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.

Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Celiac Disease
  • Dietary Supplement: Aspergillus niger prolyl endoprotease
    160 PPU daily for 2 weeks
    Other Name: AN-PEP
  • Dietary Supplement: Placebo
    Placebo
  • Experimental: ANPEP
    Aspergillus niger prolyl endoprotease (AN-PEP), a microbial-derived prolyl endoprotease which cleaves gluten
    Intervention: Dietary Supplement: Aspergillus niger prolyl endoprotease
  • Placebo Comparator: Placebo
    Intervention: Dietary Supplement: Placebo
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
14
December 2009
May 2009   (final data collection date for primary outcome measure)

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.
Both
18 Years to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
Netherlands
 
NCT00810654
RD.0601.54, NTR1281
No
C.J.Mulder, VU University Medical Center
VU University Medical Center
  • DSM Food Specialties
  • Leiden University Medical Center
Principal Investigator: Greetje J Tack, MD VU University Medical Center
VU University Medical Center
May 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP