Condition category
Musculoskeletal Diseases
Date applied
07/04/2008
Date assigned
09/05/2008
Last edited
13/02/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Jill Belch

ORCID ID

Contact details

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
Dundee
DD1 9SY
United Kingdom
+44 (0)1382 632457
j.j.f.belch@dundee.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

MTXa54 v1 04/04/05

Study information

Scientific title

Effect of folic acid supplementation and allopurinol on endothelial function in patients with rheumatoid arthritis treated with methotrexate

Acronym

Study hypothesis

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.

Ethics approval

Tayside Committee on Medical Research Ethics, 26/05/2005, ref: 05/S1401/55

Study design

Single-centre randomised double-blind placebo-controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Rheumatoid arthritis

Intervention

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.

Intervention type

Drug

Phase

Not Applicable

Drug names

Folic acid, allopurinol and methotrexate

Primary outcome measures

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)

Secondary outcome measures

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])

Overall trial start date

21/08/2006

Overall trial end date

14/03/2008

Reason abandoned

Eligibility

Participant inclusion criteria

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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

80

Participant exclusion criteria

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)

Recruitment start date

21/08/2006

Recruitment end date

14/03/2008

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Vascular and Inflammatory Diseases Research Unit
Dundee
DD1 9SY
United Kingdom

Sponsor information

Organisation

University of Dundee (UK)

Sponsor details

Research and Innovation Services
Dundee
DD1 4HN
United Kingdom
+44 (0)1382 344664
j.z.houston@dundee.ac.uk

Sponsor type

University/education

Website

http://www.dundee.ac.uk

Funders

Funder type

Charity

Funder name

Tenovus Scotland (ref: T05/31) (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Anonymous Trust, University of Dundee (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes