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

Sponsors and Collaborators:	VU University Medical Center DSM Food Specialties Leiden University Medical Center
Information provided by:	VU University Medical Center
ClinicalTrials.gov Identifier:	NCT00810654

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 I Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study
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:

MedlinePlus related topics: Celiac Disease Dietary Supplements Diets

U.S. FDA Resources

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
Estimated Study Completion Date:	May 2009
Estimated Primary Completion Date:	February 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
ANPEP: Experimental 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
Placebo: Placebo Comparator	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

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

Responsible Party:	VU University Medical Center ( C.J.Mulder )
Study ID Numbers:	RD.0601.54, NTR1281
Study First Received:	December 17, 2008
Last Updated:	May 28, 2009
ClinicalTrials.gov Identifier:	NCT00810654 History of Changes
Health Authority:	Netherlands: Independent Ethics Committee

Keywords provided by VU University Medical Center:

Celiac disease
Coeliac disease
treatment

AN-PEP
prolyl endoprotease
gluten

Study placed in the following topic categories:

Metabolic Diseases
Digestive System Diseases
Gastrointestinal Diseases
Malabsorption Syndromes

Celiac Disease
Intestinal Diseases
Metabolic Disorder

Additional relevant MeSH terms:

Metabolic Diseases
Digestive System Diseases
Gastrointestinal Diseases

Malabsorption Syndromes
Celiac Disease
Intestinal Diseases

ClinicalTrials.gov processed this record on September 03, 2009