The Influence of 5-Aminosalicylates on Thiopurine Metabolite Levels

Amsterdam UMC, location VUmc

Status and phase: Completed; Phase 4

Conditions: Inflammatory Bowel Disease; Ulcerative Colitis; Crohn's Disease

Treatments: Drug: 5-aminosalicylate (Pentasa, Ferring)

Study type: Interventional

Funder types: Other

Identifiers

NCT00167882

2005/28

Details and patient eligibility

About

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.

Full 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).

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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)

Exclusion criteria

• 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
• 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 design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: Single Blind