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The Influence of 5-Aminosalicylates on Thiopurine Metabolite Levels

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ClinicalTrials.gov Identifier: NCT00167882
Recruitment Status : Completed
First Posted : September 14, 2005
Last Update Posted : September 11, 2006
Sponsor:
Information provided by:
VU University Medical Center

Tracking Information
First Submitted Date  ICMJE September 9, 2005
First Posted Date  ICMJE September 14, 2005
Last Update Posted Date September 11, 2006
Study Start Date  ICMJE July 2005
Primary Completion Date Not Provided
Current Primary Outcome Measures  ICMJE
 (submitted: September 8, 2006)
To determine the influence of 5-ASA compounds and its metabolites on the 6-TGN level during steady state AZA or 6-MP dosages
Original Primary Outcome Measures  ICMJE
 (submitted: September 9, 2005)
1. To determine the influence of 5-ASA compounds and its metabolites on the 6-TGN level during steady state AZA or 6-MP dosages
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 8, 2006)
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: September 9, 2005)
  • 2. To determine the influence of 5-ASA compounds and its metabolites on the 6-MMP level during steady state AZA or 6-MP dosages
  • 3. 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
  • 4. To evaluate the safety of co-administrating 5-ASA and AZA or 6-MP in IBD patients
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Influence of 5-Aminosalicylates on Thiopurine Metabolite Levels
Official Title  ICMJE Not Provided
Brief 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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Single
Primary Purpose: Treatment
Condition  ICMJE
  • Crohn's Disease
  • Ulcerative Colitis
  • Inflammatory Bowel Disease
Intervention  ICMJE Drug: 5-aminosalicylate (Pentasa, Ferring)
Study Arms  ICMJE Not Provided
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Enrollment  ICMJE
 (submitted: September 9, 2005)
24
Original Enrollment  ICMJE Same as current
Study Completion Date  ICMJE August 2006
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00167882
Other Study ID Numbers  ICMJE 2005/28
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE VU University Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: K.H.N. de Boer, MD VU University Medical Center
PRS Account VU University Medical Center
Verification Date August 2006

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP