Crohn's DiseasePhase 4NCT00167882
The Influence of 5-Aminosalicylates on Thiopurine Metabolite Levels
A Phase 4 study testing 5-aminosalicylate (Pentasa, Ferring) in people with Crohn's Disease and Ulcerative Colitis, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
Trial summary
The purpose of this study is to determine the influence of different 5-aminosalicylate concentrations on the metabolism of azathioprine or 6-mercaptopurine in patients with inflammatory bowel disease. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Crohn's Disease, Ulcerative Colitis, Inflammatory Bowel Disease
- What is being tested?
- 5-aminosalicylate (Pentasa, Ferring)
- How many people
- 24 participants
- Where
- 1 siteNetherlands
- Study dates
- Jul 2005to Aug 2006
- Phase
- Phase 4
- 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
- Adult patients, aged between 18 - 70 years
- Informed consent
- Diagnosis of CD or UC for at least 6 months (histological and endoscopically confirmed)
- Steady state AZA of 6-MP use (an unchanged thiopurine regime for at least 4 weeks)
- Normal liver and kidney function (ALAT / AP / creatinin < 2 x upper normal limit)
- Quiescent disease (HBI score ≤ 4 for CD or modified TLWI score ≤ 4 for UC)
Who cannot join
- Bone marrow suppression (platelets / leucocytes < 1 x lower normal level)
- Presence of active infection (fever and CRP > 1 x upper normal limit)
- Anemia (hemoglobin < 6 mmol)
- Known duodenal Crohn's disease interfering significantly with resorptive area
- Small bowel surgery interfering significantly with resorptive area
- Known intolerance to 5-ASA compounds
Show all 10Show fewer
- Current use of 5-ASA compounds
- Use of 5-ASA compounds within the last 30 days
- Concomitant use of allopurinol, ACE-inhibitors or furosemide
- Pregnancy, expected pregnancy or lactation within 6 months
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to determine the influence of different 5-aminosalicylate concentrations on the metabolism of azathioprine or 6-mercaptopurine in patients with inflammatory bowel disease.
Read the detailed description
Background:
The concomitant use of 5-aminosalicylates (5ASA) next to azathioprine (AZA) or 6-mercaptopurine (6MP) in the treatment of inflammatory bowel disease (IBD) may lead to an increased effectiveness of therapy as higher levels of the active metabolite of AZA/6MP (6-thioguaninenucleotides (6TGNs) are measured.
Objectives:
To determine the influence of 5-ASA compounds and its metabolites on the metabolites of AZA/6MP (6TGNs + 6-methylmercaptopurine (6MMP).
Methods:
Patients with quiescent disease under AZA/6MP therapy are eligible. Patients will receive three succeeding regimes (5ASA 2 gram/5ASA 4 gram/ no 5ASA) of 4 weeks next to the standard AZA/6MP therapy. At the start and at the end of every regime 5ASA and its major metabolite (N-acetyl-5ASA) will be determined in serum next to the measurement of 6TGNs and 6MMP in erythrocytes. The safety will monitored by standard laboratory parameters every four weeks.
Population:
Patients with IBD in remission and unchanged AZA/6MP dosages for at least 4 weeks.
Medication:
5ASA (Pentasa ® granules; Ferring) will be administered orally in dosages of 2 or 4 grams daily for a period of 4 weeks.
Endpoints:
The rise or decrease in 6TGNs and 6MMP during the different 5ASA regimes. The evaluation of the safety of co-administrating 5ASA next to AZA/6MP.
Risks:
Side effects of 5ASA use are limited and well known. Some case reports have described the potential risk of developing a myelodepression when AZA/6MP and 5ASA are given together due to the rise in 6TGNs. However, in daily practice both drugs are administered together frequently. The risks of the frequent blood draws are minimal and usually self-limiting (haematoma).
- Being tested
- 5-aminosalicylate (Pentasa, Ferring)
- Keywords
- Crohn's disease, Ulcerative colitis, Inflammatory bowel disease, azathioprine, 6-mercaptopurine, 5-aminosalicylate, metabolism
- Medical subject headings
- Crohn Disease, Colitis, Ulcerative, Inflammatory Bowel Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5-aminosalicylate (Pentasa, Ferring)Drug
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the influence of 5-ASA compounds and its metabolites on the 6-TGN level during steady state AZA or 6-MP dosages
Secondary outcomes (3)
To determine the influence of 5-ASA compounds and its metabolites on the 6-MMP level during steady state AZA or 6-MP dose
To determine the influence of 5-ASA compounds and its metabolites on the 6-TGMP, 6-TGDP and 6-TGTP levels during steady state AZA or 6-MP dosages
To evaluate the safety of co-administrating 5-ASA and AZA or 6-MP in IBD patients
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2005 (estimated)
- Study startJul 2005
- Study completionAug 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Crohn's 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 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- Single blind
- Enrolment
- 24 participants
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Investigators
- K.H.N. de Boer, MD, Principal investigator, Amsterdam UMC, location VUmc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00167882
- Sponsor's protocol ID
- 2005/28
- Status last verified
- Aug 2006
- First submitted
- 9 Sep 2005
- Last updated
- 11 Sep 2006
- Results posted
- No
Publications
Derijks LJ, Gilissen LP, Engels LG, Bos LP, Bus PJ, Lohman JJ, Curvers WL, Van Deventer SJ, Hommes DW, Hooymans PM. Pharmacokinetics of 6-mercaptopurine in patients with inflammatory bowel disease: implications for therapy. Ther Drug Monit. 2004 Jun;26(3):311-8. doi: 10.1097/00007691-200406000-00016.
PubMed 15167634de Boer NK, de Graaf P, Wilhelm AJ, Mulder CJ, van Bodegraven AA. On the limitation of 6-tioguaninenucleotide monitoring during tioguanine treatment. Aliment Pharmacol Ther. 2005 Sep 1;22(5):447-51. doi: 10.1111/j.1365-2036.2005.02581.x.
PubMed 16128683Al Hadithy AF, de Boer NK, Derijks LJ, Escher JC, Mulder CJ, Brouwers JR. Thiopurines in inflammatory bowel disease: pharmacogenetics, therapeutic drug monitoring and clinical recommendations. Dig Liver Dis. 2005 Apr;37(4):282-97. doi: 10.1016/j.dld.2004.09.029.
PubMed 15788214
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2006. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Influence of 5-Aminosalicylates on Thiopurine Metabolite Levels
- ClinicalTrials.gov ID
- NCT00167882
- Acronym / sponsor ID
- 2005/28
- Keywords
- Crohn's disease, Ulcerative colitis, Inflammatory bowel disease, azathioprine, 6-mercaptopurine, 5-aminosalicylate, metabolism
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants
- Lead sponsor
- Amsterdam UMC, location VUmcUniversity, hospital or other
- Study start
- Jul 2005
- Study completion
- Aug 2006
- First posted
- 14 Sep 2005 (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.
The purpose of this study is to determine the influence of different 5-aminosalicylate concentrations on the metabolism of azathioprine or 6-mercaptopurine in patients with inflammatory bowel disease.
Detailed description
Background:
The concomitant use of 5-aminosalicylates (5ASA) next to azathioprine (AZA) or 6-mercaptopurine (6MP) in the treatment of inflammatory bowel disease (IBD) may lead to an increased effectiveness of therapy as higher levels of the active metabolite of AZA/6MP (6-thioguaninenucleotides (6TGNs) are measured.
Objectives:
To determine the influence of 5-ASA compounds and its metabolites on the metabolites of AZA/6MP (6TGNs + 6-methylmercaptopurine (6MMP).
Methods:
Patients with quiescent disease under AZA/6MP therapy are eligible. Patients will receive three succeeding regimes (5ASA 2 gram/5ASA 4 gram/ no 5ASA) of 4 weeks next to the standard AZA/6MP therapy. At the start and at the end of every regime 5ASA and its major metabolite (N-acetyl-5ASA) will be determined in serum next to the measurement of 6TGNs and 6MMP in erythrocytes. The safety will monitored by standard laboratory parameters every four weeks.
Population:
Patients with IBD in remission and unchanged AZA/6MP dosages for at least 4 weeks.
Medication:
5ASA (Pentasa ® granules; Ferring) will be administered orally in dosages of 2 or 4 grams daily for a period of 4 weeks.
Endpoints:
The rise or decrease in 6TGNs and 6MMP during the different 5ASA regimes. The evaluation of the safety of co-administrating 5ASA next to AZA/6MP.
Risks:
Side effects of 5ASA use are limited and well known. Some case reports have described the potential risk of developing a myelodepression when AZA/6MP and 5ASA are given together due to the rise in 6TGNs. However, in daily practice both drugs are administered together frequently. The risks of the frequent blood draws are minimal and usually self-limiting (haematoma).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- Single blind
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Adult patients, aged between 18 - 70 years
- Informed consent
- Diagnosis of CD or UC for at least 6 months (histological and endoscopically confirmed)
- Steady state AZA of 6-MP use (an unchanged thiopurine regime for at least 4 weeks)
- Normal liver and kidney function (ALAT / AP / creatinin < 2 x upper normal limit)
Key exclusion criteria (10 listed)
- Bone marrow suppression (platelets / leucocytes < 1 x lower normal level)
- Presence of active infection (fever and CRP > 1 x upper normal limit)
- Anemia (hemoglobin < 6 mmol)
- Known duodenal Crohn's disease interfering significantly with resorptive area
- Small bowel surgery interfering significantly with resorptive area
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 |
|---|---|---|
| 5-aminosalicylate (Pentasa, Ferring) | Drug | – |
Primary outcome
To determine the influence of 5-ASA compounds and its metabolites on the 6-TGN level during steady state AZA or 6-MP dosages
3 secondary outcomes
To determine the influence of 5-ASA compounds and its metabolites on the 6-MMP level during steady state AZA or 6-MP dose
To determine the influence of 5-ASA compounds and its metabolites on the 6-TGMP, 6-TGDP and 6-TGTP levels during steady state AZA or 6-MP dosages
To evaluate the safety of co-administrating 5-ASA and AZA or 6-MP in IBD patients
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 11 Sep 2006.
- Background: PubMed 15167634Derijks LJ, Gilissen LP, Engels LG, Bos LP, Bus PJ, Lohman JJ, Curvers WL, Van Deventer SJ, Hommes DW, Hooymans PM. Pharmacokinetics of 6-mercaptopurine in patients with inflammatory bowel disease: implications for therapy. Ther Drug Monit. 2004 Jun;26(3):311-8. doi: 10.1097/00007691-200406000-00016.
- Background: PubMed 16128683de Boer NK, de Graaf P, Wilhelm AJ, Mulder CJ, van Bodegraven AA. On the limitation of 6-tioguaninenucleotide monitoring during tioguanine treatment. Aliment Pharmacol Ther. 2005 Sep 1;22(5):447-51. doi: 10.1111/j.1365-2036.2005.02581.x.
- Background: PubMed 15788214Al Hadithy AF, de Boer NK, Derijks LJ, Escher JC, Mulder CJ, Brouwers JR. Thiopurines in inflammatory bowel disease: pharmacogenetics, therapeutic drug monitoring and clinical recommendations. Dig Liver Dis. 2005 Apr;37(4):282-97. doi: 10.1016/j.dld.2004.09.029.
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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.
K.H.N. de Boer, 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 4 study testing 5-aminosalicylate (Pentasa, Ferring) in people with Crohn's Disease and Ulcerative Colitis, 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 6 inclusion and 10 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 11 Sep 2006. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
To determine the influence of 5-ASA compounds and its metabolites on the 6-TGN level during steady state AZA or 6-MP dosages. 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 NCT00167882, which also lists 3 linked publications.
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 11 Sep 2006.