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ISRCTN
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ISRCTN22788282
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ClinicalTrials.gov identifier
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Public title
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Effect of folic acid supplementation and allopurinol on blood vessel health in patients with rheumatoid arthritis
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Scientific title
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Effect of folic acid supplementation and allopurinol on endothelial function in patients with rheumatoid arthritis treated with methotrexate
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Acronym
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N/A
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Serial number at source
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MTXa54 v1 04/04/05
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Study hypothesis
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Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder characterized by a symmetrical erosive polyarthritis with inflammatory multisystemic involvement. Most patients exhibit a chronic fluctuating course of disease that, if left untreated, results in progressive joint destruction, deformity, and disability. The patient with RA has their life span shortened by 15-20% with up to 40% of excess deaths being due to cardiovascular disease.
Study aim:
To evaluate whether endothelial function and other surrogate markers of cardiovascular disease can be improved by the addition of extra folic Acid (above the dose conventionally given) and allopurinol (which attenuates oxidative stress) in patients with RA taking methotrexate.
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Ethics approval
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Tayside Committee on Medical Research Ethics. Date of approval: 26/05/2005 (ref: 05/S1401/55)
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Study design
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Single-centre, randomised, double-blind placebo-controlled trial.
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Countries of recruitment
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United Kingdom
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Disease/condition/study domain
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Rheumatoid arthritis
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Participants - inclusion criteria
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1. Both males and females, 18 years old or over
2. Fulfil the 1987 American College of Rheumatology (ACR) classification criteria for RA
3. On methotrexate for at least 6 months
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Participants - exclusion criteria
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1. Previous cardiovascular or cerebrovascular events in the last 3 years
2. Undergoing treatment for a cardiovascular risk factor except:
2.1. Patients with hypertension on stable medication for the last 3 months
2.2. Patients with hypercholesterolemia on stable medication for the last 3 months
3. Contraindications to allopurinol (moderate to severe renal impairment, liver impairment, concomitant treatment with azathioprine, known allergy to allopurinol)
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Anticipated start date
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21/08/2006
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Anticipated end date
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14/03/2008
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Status of trial
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Completed
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Patient information material
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Target number of participants
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80
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Interventions
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The participants will be randomised to the following:
Control group: 5 mg of folic acid (oral) once a week as per methotrexate protocol
"Active" group: 5 mg of folic acid (oral) 7 days a week (extra folic acid)
At 4 months, both groups will be randomised again to receive either allopurinol (oral) 300 mg a day or placebo in addition to their folate/control medication for 8 weeks.
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Primary outcome measure(s)
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Endothelial function measured by the following at baseline, 4 and 6 months:
1. Laser Doppler flowmetry after iontophoretic delivery of acetylcholine and sodium nitroprusside
(microvascular)
2. Brachial artery flow mediated dilatation (macrovascular)
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Secondary outcome measure(s)
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The following were assessed at baseline, 4 and 6 months:
1. Endothelial function measured by blood testing of vascular function and damage (E selectin, thrombomodulin)
2. Arterial stiffness measured by applanation tonometry
3. Oxidative stress (Isoprostane levels)
4. Serum homocysteine, folic acid and uric acid levels
5. RA disease activity (28-item Disease Activity Score [DAS28], Health Assessment Questionnaire [HAQ], the 36-item short form health survey [SF-36])
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Sources of funding
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1. Tenovus Scotland (ref: T05/31) (UK)
2. Anonymous Trust, University of Dundee (UK)
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Trial website
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Publications
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Contact name
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Prof
Jill
Belch
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Address
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Vascular and Inflammatory Diseases Research Unit
The Institute of Cardiovascular Research
University Division of Medicine and Therapeutics
Ninewells Hospital and Medical School
University of Dundee
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City/town
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Dundee
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Zip/Postcode
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DD1 9SY
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Country
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United Kingdom
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Tel
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+44 (0)1382 632457
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Fax
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+44 (0)1382 632333
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Email
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j.j.f.belch@dundee.ac.uk
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Sponsor
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University of Dundee (UK)
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Address
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Research and Innovation Services
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City/town
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Dundee
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Zip/Postcode
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DD1 4HN
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Country
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United Kingdom
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Tel
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+44 (0)1382 344664
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Fax
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+44 (0)1382 202178
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Email
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j.z.houston@dundee.ac.uk
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Sponsor website:
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http://www.dundee.ac.uk
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Date applied
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07/04/2008
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Last edited
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09/05/2008
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Date ISRCTN assigned
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09/05/2008
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