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

Celiac Disease Clinical Trial

Official title:

Study on The Effectiveness of Oral Administration of Prolyl Endoprotease for Gluten Detoxification as a Means to Treat Coeliac Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00810654
• Other study ID #: RD.0601.54
• Secondary ID: NTR1281
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: December 17, 2008
• Last updated: January 18, 2011
• Start date: May 2008
• Est. completion date: December 2009

Study information

• Verified date: May 2009
• Source: VU University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Independent Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: December 2009
• Est. primary completion date: May 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Celiac Disease

Intervention

Dietary Supplement:
• Aspergillus niger prolyl endoprotease
160 PPU daily for 2 weeks
• Placebo
Placebo

Locations

Country	Name	City	State
Netherlands	VU University Medical Center	Amsterdam

Sponsors (3)

Lead Sponsor	Collaborator
VU University Medical Center	DSM Food Specialties, Leiden University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Histopathological changes according to the Modified Marsh criteria		One week before start, and 2 and 6 weeks after start	No
Primary	The presence of coeliac disease specific antibodies (EMA, tTGA, gliadin)		One week before start, and 2 and 6 weeks after start	No
Secondary	Presence and activity of gluten reactive Tcells isolated from biopsies and serum		One week before start, and 2 and 6 weeks after start	No
Secondary	Immunophenotype of lymphocytes isolated from biopsies		One week before start, and 2 and 6 weeks after start	No
Secondary	Clinical symptoms after gluten intake with and without AN-PEP		One week before start, and 2 and 6 weeks after start	No