Primary objective: Investigating whether 50 mg allopurinol is non-inferior to 100 mg in combination with azathioprine or mercaptopurine by measuring and comparing thiopurine metabolites Secondary objectives:-Comparing patient tolerability in terms…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- 6-TGN and 6-MMP concentrations
These are the metabolites of the thiopurine that is being used by a patient.
The concentrations before and after the intervention will be measured with (a
validated) UPLC-analysis.
Secondary outcome
-Incidence of adverse events
The incidence of adverse events before and after the intervention will be
compared.
-Allopurinol concentrations
Allopurinol concentrations will be measured with a validated HPLC-analysis.
-Enzyme activity XO, TPMT and HPRT
These enzymes are involved in the metabolism of thiopurines and their
metabolites. The enzyme activity of these enzymes will be measured with a
validated enzyme assay (HPLC and radioactivity).
-Disease activity (HBI scores for Crohn's and Mayo scores for Colitis Ulcerosa,
CRP, faecal calprotecin)
The HBI and Mayo score are validated and widely used scoring tools for defining
disease activity of patients with respectively Crohn's and CU. These two
indices will also be used within this study population to compare disease
activity before and after the intervention.
Other parameters:
-Thiopurine (azathioprine or mercaptopurine) dose
-Duration of previous allopurinol 100 mg usage
-Indication of thiopurine (Crohn's or Colitis Ulcerosa)
Background summary
Crohn's disease and Colitis Ulcerosa patients frequently use a thiopurine
(azathioprine or mercaptopurine) to reduce disease activity. These drugs are
metabolised in a few metabolites, including 6-thioguanine (6-TGN) and
6-methylmercaptopurine (6-MMP).
Therapeutic 6-TGN concentrations correlate with the efficacy of thiopurines,
while 6-MMP and 6-TGN concentrations that are too high can lead to hepato- en
myelotoxicity (liver disease, trombocytopena, anemia, pancreatitis en
leucopenia).
About 25% of thiopurine users has non-therapeutic 6-TGN and/or supratherapeutic
6-MMP concentrations with a 6-MMP/6-TGN ratio > 10. These patients are normally
treated with additional allopurinol 100 mg once daily, because allopurinol
interferes with the metabolism of thiopurines by inhibiting the enzym xanthine
oxidase (XO). The dosage of the thiopurine is then lowered to ~25-33% of the
original dose. This intervention causes the metabolism to shift from mainly
6-MMP to 6-TGN and causes an improvement of the 6-MMP/6-TGN ratio. A number of
studies has shown previously that this intervention is safe and effective in
daily practice.
In our hospital, Meander Medical Center, a part of our patients who are using
allopurinol 100 mg once a day does not tolerate this drug. A recent study has
shown that 50 mg of allopurinol might be equally effective as 100 mg, and might
be better tolerated. In the current study this will be investigated
intrapatiënt by giving the same patients 50 mg allopurinol instead of 100 mg.
This study can lead to better understandig of the effectiveness and
tolerability of allopurinol 50 mg so that patients are not unnecessarily
exposed to a high dose of allopurinol.
Study objective
Primary objective:
Investigating whether 50 mg allopurinol is non-inferior to 100 mg in
combination with azathioprine or mercaptopurine by measuring and comparing
thiopurine metabolites
Secondary objectives:
-Comparing patient tolerability in terms of adverse events
-comparing allopurinol concentrations
-comparing enzyme activity for XO, TPMT and HRPT
-comparing disease activity (HBI and Mayo scores, CRP, faecal calprotectin)
Study design
a prospective one way cross-over study
Intervention
Reducing the dose of allopurinol: from 100 to 50 mg once a day
Study burden and risks
Evaluation of burden and risks:
-Patients will be seen in our hospital during their regular, existing
appointments (polyclinical).
-Only additional blood will be taken from patients during their existing
polyclinical and laboratory analysis appointments.
-Patients will be asked about their experience, just as in daily practice.
-Recently performed research has proven the safety of a similar intervention.
Maatweg 3
Amersfoort 3813 TZ
NL
Maatweg 3
Amersfoort 3813 TZ
NL
Listed location countries
Age
Inclusion criteria
-Crohn's disease or Colitis Ulcerosa
-At least one month perior usage of 100 mg allopurinol daily with azathioprine or mercaptopurine
-Stable response and adequate concentrations on combination therapy with a thiopurine and allopurinol
-No recent (<1 month) changes in thiopurine dosage
-At least 18 years old
Exclusion criteria
-Age below 18 years old
-Pregnancy
-Hypersensitivity to azathioprine, mercaptopurine and/or allopurinol
-Severe anemia, leukopenia or thrombocytopenia
-Lesch-Nyhan syndrome
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| EudraCT | EUCTR2016-001638-84-NL |
| CCMO | NL57653.100.16 |