To determine if AN-PEP is capable of detoxifying gluten in vivo in patients diagnosed with coeliac disease
ID
Source
Brief title
Condition
- Gastrointestinal disorders
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To investigate in vivo AN-PEP activity, small intestinal biopsy material will
be analysed for the following:
* Histopathological changes according to the Modified Marsh criteria.
* The presence and activity of gluten reactive T cells isolated from biopsies.
* The immunophenotype of lymphocytes (IEL and LPL) isolated from biopsies.
To investigate in vivo AN-PEP activity, peripheral blood samples will be
analysed for the following:
* The presence and activity of gluten reactive T cells.
* The presence of coeliac disease specific antibodies (EMA, tTGA).
Secondary outcome
Not applicable
Background summary
Coeliac disease is a small intestinal disease caused by inflammatory T cell
responses to proline-rich peptides derived from gluten molecules in wheat and
related cereals. Due to the high proline content gluten peptides are resistant
to degradation in the gastrointestinal tract. Oral supplementation with enzymes
that can cut gluten has therefore been suggested as a potential treatment
modality for coeliac disease. In the present study we wish to determine if
co-administration of such an enzyme to a gluten containing meal can prevent the
occurrence of coeliac disease specific symptoms and be therefore a suitable
alternative to a gluten-free diet. In particular we wish to determine if 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.
Study objective
To determine if AN-PEP is capable of detoxifying gluten in vivo in patients
diagnosed with coeliac disease
Study design
Randomised double-blinded semi-cross-over design
This study includes three two-week periods.
1st Period: Patients are given a commercial food product containing 8 grams of
gluten, to which AN-PEP has been added, once daily.
2nd Period: Wash-out period of fourteen days. During this period all patients
will use gluten free diet.
3rd Period: Patients who are negative for coeliac disease symptoms during the
1st period will be randomised in two groups. The first group receives a
commercial food product containing 8 grams of gluten, to which AN-PEP has been
added, once daily. The second group receives the same product to which placebo
has been added.
Intervention
Not applicable
Study burden and risks
Patients are expected to pay five visits to the out-patient clinic of the
department of gastroenterology of the VU university medical center.
During three of the visits 12 spike-biopsies will be taken from the duodenum
during oesophago-gastro-duodenoscopy. 5 blood samples (10ml) will be taken
during all of the five visits.
Patients will be asked to fill in a questionnaire at the start of the study, at
the end of the first period and at the start and end of the last period of the
study, concerning the quality of life score.
During the first period patients will be asked to consume a gluten containing
commercial food product to which AN-PEP has been added, once daily. In the
third period of this study patients will be asked to consume the same food
product to which AN-PEP or placebo has been added.
There are no known or expected risks associated with the ingestion of gluten
during the course of the study other than the coeliac disease specific
symptoms. In fact, a gluten challenge is used as part of the diagnostic
procedure for coeliac disease. No adverse effects are expected with venous
puncture.
Studies have shown that 6 to 10 mucosal biopsies (3 * 6 mg) can be taken
without any side effects. No perforations have been described with this
technique and there is no indication that this leads to major bleeding.
AN-PEP has been tested extensively in a toxicology program. No hypersensitivity
reactions have been found in previous human feeding studies with this type of
food grade enzymes.
P.O. Box 1
2600 MA Delft
Nederland
P.O. Box 1
2600 MA Delft
Nederland
Listed location countries
Age
Inclusion criteria
* Confirmed diagnosis of coeliac disease (Marsh III B/C)
* 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 duodenum descendents;
* 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.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL21084.029.08 |