The Influence of Methotrexate on the Metabolism and Vascular Effects of Adenosine in Humans

Vasodilation Clinical Trial

Official title:

The Influence of Methotrexate on the Metabolism and Vascular Effects of Adenosine in Humans

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00184886
• Other study ID #: MTX-Ado
• Secondary ID: ZonMw Nr. 920-03
• Status: Completed
• Phase: N/A
• First received: September 12, 2005
• Last updated: February 13, 2006
• Start date: November 2003
• Est. completion date: January 2005

Study information

• Verified date: February 2006
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: January 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Methotrexate
• Vasodilation

Intervention

Drug:
• Methotrexate 15 mg/week for 12 weeks

Locations

Country	Name	City	State
Netherlands	Radboud University Nijmegen Medical Centre	Nijmegen

Sponsors (2)

Lead Sponsor	Collaborator
Radboud University	ZonMw: The Netherlands Organisation for Health Research and Development

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Vasodilator response to infusion of adenosine and dipyridamole into the brachial artery
Secondary	Adenosine deaminase activity
Secondary	CRP, BSE, DAS