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The Influence of 5–Aminosalicylates on Thiopurine Metabolite Levels

This study has been completed.
Sponsor:
Information provided by:
VU University Medical Center
ClinicalTrials.gov Identifier:
NCT00167882
First received: September 9, 2005
Last updated: September 8, 2006
Last verified: August 2006
History of Changes
  Purpose

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.


Condition Intervention Phase
Crohn's Disease
Ulcerative Colitis
Inflammatory Bowel Disease
 Drug: 5-aminosalicylate (Pentasa, Ferring)
 Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Single Blind
Primary Purpose: Treatment

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by VU University Medical Center:

Primary Outcome Measures:
  • 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 Outcome Measures:
  • 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

Estimated Enrollment: 24
Study Start Date: July 2005
Estimated Study Completion Date: August 2006
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).

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00167882

Locations
Netherlands
Maasland Hospital
Sittard, Netherlands
Sponsors and Collaborators
VU University Medical Center
Investigators
Principal Investigator: K.H.N. de Boer, MD VU University Medical Center
  More Information

Publications:

ClinicalTrials.gov Identifier: NCT00167882     History of Changes
Other Study ID Numbers: 2005/28
Study First Received: September 9, 2005
Last Updated: September 8, 2006
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by VU University Medical Center:
Crohn's disease
Ulcerative colitis
Inflammatory bowel disease
azathioprine
 6-mercaptopurine
5-aminosalicylate
metabolism

Additional relevant MeSH terms:
Colitis
Colitis, Ulcerative
Crohn Disease
Inflammatory Bowel Diseases
Intestinal Diseases
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Pathologic Processes
Mesalamine
 Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on May 16, 2013