|- candidate number||3213|
|- NTR Number||NTR1281|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||18-apr-2008|
|- Secondary IDs||20080328-ANP |
|- Public Title||Effect of AN-PEP enzyme on the effects of gluten ingestion in patients with coeliac disease|
|- Scientific Title||Effect of AN-PEP enzyme on the effects of gluten ingestion in patients with coeliac disease|
|- hypothesis||Determine whether AN-PEP enzyme is effective in mitigating the effects of 8 g wheat protein ingestion in patients with celiac disease|
|- Healt Condition(s) or Problem(s) studied||Coeliac disease , Gluten, AN-PEP enzyme |
|- Inclusion criteria||1. 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. |
2. Detectable coeliac disease specific antibodies (EMA, tTGA) at time of diagnosis.
3. A strict gluten free diet for at least 1 year and normalised villous architecture (Marsh 0/I).
4. Male and female, 18-70 years old.
5. No detectable anti-endomysium and low anti-tissue transglutaminase (<4 U/ml) prior to the start of the study.
6. 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.
7. Patient has read the information provided on the study and given written consent;
8. Female participants at fertile age must use adequate contraception.
|- Exclusion criteria||1. Use of any immunoregulatory drug within the last 6 months|
2. Use of any anticoagulant drug
3. Clinically suspected bleeding tendency
4. Pregnancy or breast feeding
5. Presence of any concurrent active infection
6. IgA deficiency
7. Use of medication within 8 hour prior to intervention
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||2 or more arms, randomized|
|- planned startdate ||5-mei-2008|
|- planned closingdate||15-apr-2009|
|- Target number of participants||14|
|- Interventions||Patients will consume 8 g wheat protein daily with AN-PEP enzyme for 14 d. After a 14-d washout period, patients who are negative for coeliac disease symptoms during the 1st period will randomly receive 8 g wheat protein daily with AN-PEP enzyme or placebo for another 14 d.|
|- Primary outcome||Immunohistopathological changes in small intestinal biopsies to diagnose coeliac disease|
|- Secondary outcome||- Gluten reactive T cells|
- Coeliac disease specific antibodies
- Coeliac disease-associated clinical symptoms (questionnaire) to diagnose coeliac disease
|- Timepoints||Before and after 2-week intake period|
|- Trial web site||N/A|
|- status||stopped: trial finished|
|- CONTACT FOR PUBLIC QUERIES||Prof. Dr. C.J. Mulder|
|- CONTACT for SCIENTIFIC QUERIES||Prof. Dr. F. Koning|
|- Sponsor/Initiator ||DSM Food Specialties|
(Source(s) of Monetary or Material Support)
|DSM Food Specialties|
|- Brief summary||Rationale: |
Coeliac disease is an autoimmune disorder of the small bowel and is caused by a reaction to a gluten protein found in wheat. Gluten proteins are resistant to degradation in the gastrointestinal tract.
The AN-PEP enzyme was shown to degrade gluten in an in vitro digestion model.
Determine whether AN-PEP enzyme is effective in mitigating the effects of gluten ingestion in patients with celiac disease
Randomised double-blinded semi-cross-over design
Fourteen patients with coeliac disease, 18-70 years old
This study consists of three 14-d periods.
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 randomised 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 groups receives the placebo.
- Primary study parameters:
Small intestinal biopsy material will be analysed for the following:
1. Histopathological changes according to the Modified Marsh criteria
2. The presence and activity of gluten reactive T cells isolated from biopsies
3. The immunophenotype of lymphocytes (IEL and LPL) isolated from biopsies
- Secondary study parameters:
Peripheral blood samples will be analysed for the following:
1. The presence and activity of gluten reactive T cells
2. The presence of coeliac disease specific antibodies (EMA, tTGA)
3. The presence of coeliac disease- associated clinical symptoms based on a quality of life questionnaire
|- Main changes (audit trail)|
|- RECORD||18-apr-2008 - 12-jul-2009|