Effect of folic acid supplementation and allopurinol on blood vessel health in patients with rheumatoid arthritis
| ISRCTN | ISRCTN22788282 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN22788282 |
| Protocol serial number | MTXa54 v1 04/04/05 |
| Sponsor | University of Dundee (UK) |
| Funders | Tenovus Scotland (ref: T05/31) (UK), Anonymous Trust, University of Dundee (UK) |
- Submission date
- 07/04/2008
- Registration date
- 09/05/2008
- Last edited
- 21/06/2017
- Recruitment status
- Stopped
- Overall study status
- Stopped
- Condition category
- Musculoskeletal Diseases
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English summary of protocol
Not provided at time of registration
Contact information
Prof Jill Belch
Scientific
Scientific
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
| Phone | +44 (0)1382 632457 |
|---|---|
| j.j.f.belch@dundee.ac.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Single-centre randomised double-blind placebo-controlled trial |
| Secondary study design | Randomised controlled trial |
| Study type | Participant information sheet |
| Scientific title | Effect of folic acid supplementation and allopurinol on endothelial function in patients with rheumatoid arthritis treated with methotrexate |
| Study objectives | 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(s) | Tayside Committee on Medical Research Ethics, 26/05/2005, ref: 05/S1401/55 |
| Health condition(s) or problem(s) studied | 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 / device / biological / vaccine name(s) | Folic acid, allopurinol and methotrexate |
| Primary outcome measure(s) | 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) |
| Key secondary outcome measure(s) | 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]) |
| Completion date | 14/03/2008 |
| Reason abandoned (if study stopped) | Lack of funding/sponsorship |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | All |
| Target sample size at registration | 80 |
| Key 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 |
| Key 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) |
| Date of first enrolment | 21/08/2006 |
| Date of final enrolment | 14/03/2008 |
Locations
Countries of recruitment
- United Kingdom
- Scotland
Study participating centre
Vascular and Inflammatory Diseases Research Unit
Dundee
DD1 9SY
United Kingdom
DD1 9SY
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
21/06/2017: PI advised that this study was abandoned due to a lack of funding.
07/06/2017: No publications found in PubMed, verifying study status with principal investigator.
