Methotrexate, Vasodilation
Conditions
Brief 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.
Interventions
DRUGMethotrexate 15 mg/week for 12 weeks
Sponsors
ZonMw: The Netherlands Organisation for Health Research and Development
Radboud University Medical Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Vasodilator response to infusion of adenosine and dipyridamole into the brachial artery | — |
Secondary
| Measure | Time frame |
|---|---|
| Adenosine deaminase activity | — |
| CRP, BSE, DAS | — |
Countries
Netherlands
Outcome results
None listed