Celiac DiseasePhase 1/2NCT00810654
Effect of Aspergillus Niger Prolyl Endoprotease (AN-PEP) Enzyme on the Effects of Gluten Ingestion in Patients With Coeliac Disease
A Phase 1/2 study testing Aspergillus niger prolyl endoprotease in people with Celiac Disease, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Celiac Disease
- What is being tested?
- Aspergillus niger prolyl endoprotease
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- 1 siteNetherlands
- Study dates
- May 2008to Dec 2009
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Study on The Effectiveness of Oral Administration of Prolyl Endoprotease for Gluten Detoxification as a Means to Treat Coeliac Disease
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.
Read the 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
- Being tested
- Aspergillus niger prolyl endoprotease, Placebo
- Keywords
- Celiac disease, Coeliac disease, treatment, AN-PEP, prolyl endoprotease, gluten
- Medical subject headings
- Celiac Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aspergillus niger prolyl endoproteaseDietary supplement
Also called AN-PEP
160 PPU daily for 2 weeks
PlaceboDietary supplement
Placebo
| Study group | Role | What they receive |
|---|---|---|
| ANPEP | Experimental | Aspergillus niger prolyl endoprotease (AN-PEP), a microbial-derived prolyl endoprotease which cleaves gluten Receives: Dietary Supplement: Aspergillus niger prolyl endoprotease |
| Placebo | Placebo comparator | Not described Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Histopathological changes according to the Modified Marsh criteria
Measured: One week before start, and 2 and 6 weeks after start
The presence of coeliac disease specific antibodies (EMA, tTGA, gliadin)
Measured: One week before start, and 2 and 6 weeks after start
Secondary outcomes (3)
Presence and activity of gluten reactive Tcells isolated from biopsies and serum
Measured: One week before start, and 2 and 6 weeks after start
Immunophenotype of lymphocytes isolated from biopsies
Measured: One week before start, and 2 and 6 weeks after start
Clinical symptoms after gluten intake with and without AN-PEP
Measured: One week before start, and 2 and 6 weeks after start
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2008 (estimated)
- Study startMay 2008
- Primary completionMay 2009
- Study completionDec 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Celiac DiseaseStudies of the same condition, open and under way.
- More trials run by Amsterdam UMC, location VUmcThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 14 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Collaborators
- DSM Food Specialties, Leiden University Medical Center
- Investigators
- Greetje J Tack, MD, Principal investigator, Amsterdam UMC, location VUmc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00810654
- Sponsor's protocol ID
- RD.0601.54
- Other IDs
- NTR1281
- Status last verified
- May 2009
- First submitted
- 17 Dec 2008
- Last updated
- 19 Jan 2011
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 24124328
Study at a glance
From the registry record, last updated by the sponsor on 19 Jan 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study on The Effectiveness of Oral Administration of Prolyl Endoprotease for Gluten Detoxification as a Means to Treat Coeliac Disease
- ClinicalTrials.gov ID
- NCT00810654
- Acronym / sponsor ID
- RD.0601.54
- Conditions
- Celiac Disease
- Keywords
- Celiac disease, Coeliac disease, treatment, AN-PEP, prolyl endoprotease, gluten
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (estimated)
- Lead sponsor
- Amsterdam UMC, location VUmcUniversity, hospital or other
- Collaborators
- DSM Food Specialties, Leiden University Medical Center
- Study start
- May 2008
- Primary completion
- May 2009 (actual)
- Study completion
- Dec 2009 (actual)
- First posted
- 18 Dec 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ANPEP | Experimental | Dietary Supplement: Aspergillus niger prolyl endoproteaseAspergillus niger prolyl endoprotease (AN-PEP), a microbial-derived prolyl endoprotease which cleaves gluten |
| Placebo | Placebo comparator | Dietary Supplement: Placebo |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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;
Key exclusion criteria (6 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Aspergillus niger prolyl endoproteaseAlso: AN-PEP160 PPU daily for 2 weeks | Dietary supplement | ANPEP |
| PlaceboPlacebo | Dietary supplement | Placebo |
Primary outcome
Histopathological changes according to the Modified Marsh criteria
Time frame: One week before start, and 2 and 6 weeks after start
The presence of coeliac disease specific antibodies (EMA, tTGA, gliadin)
Time frame: One week before start, and 2 and 6 weeks after start
3 secondary outcomes
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
Immunophenotype of lymphocytes isolated from biopsies
Time frame: One week before start, and 2 and 6 weeks after start
Clinical symptoms after gluten intake with and without AN-PEP
Time frame: One week before start, and 2 and 6 weeks after start
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jan 2011.
- Derived from this study: PubMed 24124328Tack 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Greetje J Tack, MD principal investigator
Amsterdam UMC, location VUmc
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Aspergillus niger prolyl endoprotease in people with Celiac Disease, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Jan 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Histopathological changes according to the Modified Marsh criteria (time frame: One week before start, and 2 and 6 weeks after start). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00810654, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jan 2011.