Official Title: “The Influence of Methotrexate on the Metabolism and Vascular Effects of Adenosine in Humans”

In this study we aim to determine whether methotrexate influences the metabolism and vascular effects of adenosine in humans in vivo. Adenosine is an endogenous purine-nucleoside with potent anti-inflammatory effects. Also, adenosine receptor stimulation induces vasodilation, ischaemic preconditioning and many other cardiovacular effects. Previous animal studies have provided limited evidence that the anti-inflammatory effects of methotrexate are mediated by adenosine receptor stimulation. In this study, we aim to determine whether also in humans in vivo, methotretate influences endogenous adenosine. Therefore, 10 patients with inflammatory arthritis are treated with methotretxae (15 mg/week orally) for 12 weeks. Before and after treatment, vasodilation to the infusion of adenosine and dipyridamole into the brachial artery is assessed as biomarker for the endogenous adenosine concentration.

Also, blood is drawn for the determination of CRP, ESR, Adenosine deaminase activity adn homocysteine.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Pharmacokinetics/Dynamics Study

Intervention(s) in this Clinical Trial

• Drug: Methotrexate 15 mg/week for 12 weeks

Primary Measures

• Vasodilator response to infusion of adenosine and dipyridamole into the brachial artery

Secondary Measures

• Adenosine deaminase activity
• CRP, BSE, DAS

Inclusion Criteria:

• 18-75 year
• polyarthritis
• DAS score > 2.5

Exclusion Criteria:

• previous use of MTX
• concomitant use of dipyridamole/sulfazalasine
• Alcohol > 21 U/week
• elevated liver enzymes
• pregnancy, breast-feeding, asthma, renal insufficiency, thrombocytopenia, leucocytopenia

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Radboud University

Overall Clinical Trial Officials and Contacts

Gerard Rongen, MD, PhD Principal Investigator Radboud University  

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00184886

Study ID Number: MTX-Ado

ClinicalTrials.gov Identifier: NCT00184886

Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)