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

This study has been completed.
Sponsor:
Collaborator:
ZonMw: The Netherlands Organisation for Health Research and Development
Information provided by:
Radboud University
ClinicalTrials.gov Identifier:
NCT00184886
First received: September 12, 2005
Last updated: February 13, 2006
Last verified: February 2006
History of Changes
  Purpose

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.


Condition Intervention
Methotrexate
Vasodilation
 Drug: Methotrexate 15 mg/week for 12 weeks

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Influence of Methotrexate on the Metabolism and Vascular Effects of Adenosine in Humans

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Radboud University:

Primary Outcome Measures:
  • Vasodilator response to infusion of adenosine and dipyridamole into the brachial artery

Secondary Outcome Measures:
  • Adenosine deaminase activity
  • CRP, BSE, DAS

Estimated Enrollment: 10
Study Start Date: November 2003
Estimated Study Completion Date: January 2005
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00184886

Locations
Netherlands
Radboud University Nijmegen Medical Centre
Nijmegen, Netherlands, 6500HB
Sponsors and Collaborators
Radboud University
ZonMw: The Netherlands Organisation for Health Research and Development
Investigators
Principal Investigator: Gerard Rongen, MD, PhD Radboud University
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00184886     History of Changes
Other Study ID Numbers: MTX-Ado, ZonMw Nr. 920-03-249
Study First Received: September 12, 2005
Last Updated: February 13, 2006
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Additional relevant MeSH terms:
Adenosine
Methotrexate
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anti-Arrhythmia Agents
Cardiovascular Agents
Vasodilator Agents
Abortifacient Agents, Nonsteroidal
 Abortifacient Agents
Reproductive Control Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on May 22, 2013