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

NCT ID: NCT00810654

Last Updated: 2011-01-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-05-31
• Study Completion Date: 2009-12-31

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.

Conditions

Celiac Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

ANPEP

Aspergillus niger prolyl endoprotease (AN-PEP), a microbial-derived prolyl endoprotease which cleaves gluten

Group Type: EXPERIMENTAL

Aspergillus niger prolyl endoprotease

Intervention Type: DIETARY_SUPPLEMENT

160 PPU daily for 2 weeks

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DIETARY_SUPPLEMENT

Placebo

Interventions

Aspergillus niger prolyl endoprotease

160 PPU daily for 2 weeks

Intervention Type: DIETARY_SUPPLEMENT

Placebo

Placebo

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

AN-PEP

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

DSM Food Specialties

INDUSTRY

Sponsor Role: collaborator

Leiden University Medical Center

OTHER

Sponsor Role: collaborator

Amsterdam UMC, location VUmc

OTHER

Sponsor Role: lead

Responsible Party

VU University Medical Center

Principal Investigators

Greetje J Tack, MD

Role: PRINCIPAL_INVESTIGATOR

Amsterdam UMC, location VUmc

Locations

VU University Medical Center

Amsterdam, , Netherlands

Countries

Netherlands

References

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.

Reference Type: DERIVED

PMID: 24124328 (View on PubMed)

Other Identifiers

NTR1281

Identifier Type: -

Identifier Source: secondary_id

RD.0601.54

Identifier Type: -

Identifier Source: org_study_id