The Influence of 5–Aminosalicylates on Thiopurine Metabolite Levels - Full Text View

Sponsor:	VU University Medical Center
Information provided by:	VU University Medical Center
ClinicalTrials.gov Identifier:	NCT00167882

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 IV

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Single Blind, Uncontrolled, Single Group Assignment, Pharmacokinetics/Dynamics Study

Resource links provided by NLM:

Genetics Home Reference related topics: Crohn disease

MedlinePlus related topics: Crohn's Disease Ulcerative Colitis

Drug Information available for: Mesalamine

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:

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.

Boer NK, Graaf P, Wilhelm AJ, Mulder CJ, Bodegraven AA. On the limitation of 6-tioguaninenucleotide monitoring during tioguanine treatment. Aliment Pharmacol Ther. 2005 Sep 1;22(5):447-51.

Al 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.

Study ID Numbers:	2005/28
Study First Received:	September 9, 2005
Last Updated:	September 8, 2006
ClinicalTrials.gov Identifier:	NCT00167882 History of Changes
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:

Anti-Inflammatory Agents
Gastrointestinal Diseases
Mesalamine
Ulcer
Physiological Effects of Drugs
Colonic Diseases
Inflammatory Bowel Diseases
Colitis, Ulcerative
Intestinal Diseases
Pharmacologic Actions
Digestive System Diseases
Pathologic Processes

Sensory System Agents
Analgesics, Non-Narcotic
Therapeutic Uses
Crohn Disease
Anti-Inflammatory Agents, Non-Steroidal
Peripheral Nervous System Agents
Analgesics
Antirheumatic Agents
Gastroenteritis
Central Nervous System Agents
Colitis

ClinicalTrials.gov processed this record on November 25, 2009