Effect of anti-tumour necrosis factor alpha (TNFα) therapy on blood vessel health in patients with rheumatoid arthritis
| ISRCTN | ISRCTN57761809 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN57761809 |
| Secondary identifying numbers | ETADA90 v1 |
- Submission date
- 07/04/2008
- Registration date
- 09/05/2008
- Last edited
- 02/02/2015
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Musculoskeletal Diseases
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
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
| Study design | Observational open-label single-centre study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cohort study |
| Study setting(s) | Not specified |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | Effect of anti-tumour necrosis factor alpha (TNFα) therapy on endothelial function and other surrogate markers of cardiovascular disease in patients with rheumatoid arthritis |
| 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 34-40% of excess deaths being due to cardiovascular disease. Study aim: To assess the effect of the TNFa blocking drug etanercept and adalimumab on endothelial dysfunction and other surrogate markers of cardiovascular diseases in patients with RA. We hypothesised that the biologic drugs have the potential to improve endothelial dysfunction and other surrogate markers of cardiovascular disease (CVD) in patients with RA. We believe that if etanercept and adalimumab can improve endothelial dysfunction in RA patients they may be able to reduce the cardiovascular morbidity and mortality seen in this group of patients. |
| Ethics approval(s) | Tayside Committee on Medical Research Ethics. Date of approval: 05/09/2005 (ref: 05/S1401/112) |
| Health condition(s) or problem(s) studied | Rheumatoid arthritis |
| Intervention | This is an observational study. The drugs are prescribed by the rheumatology team, and this study assesses the impact of those drugs on blood vessel health. 90 RA patients (30 due to be started on methotrexate, 30 due to be started on etanercept and 30 due to be started on adalimumab) will be recruited from rheumatology clinics throughout Tayside. Treatment allocation (etanercept, adalimumab or methotrexate) will be decided by the rheumatologists in the clinic. The drugs are normally prescribed as: Etanercept: Subcutaneous injections 25 mg twice a week or 50 mg once a week Adalimumab: Subcutaneous injections 40 mg every other week Methotrexate: Orally once a week. Doses range from 7.5 mg a week to 25 mg a week Surrogate markers of cardiovascular disease will be measured at baseline (before commencement of methotrexate/ etanercept/ adalimumab), 2 months and at 4 months. |
| Intervention type | Other |
| Primary outcome measure | Endothelial function measured by the following at baseline, 2 and 4 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, 2 and 4 months: 1. Endothelial function measured by blood testing of vascular function and damage (E selectin, thrombomodulin) 2. Arterial stiffness measured by ultrasound echo tracking and applanation tonometry 3. Oxidative stress (Isoprostane levels) 4. RA disease activity (28-item Disease Activity Score [DAS28], Health Assessment Questionnaire [HAQ], 36-item Short Form health survey [SF-36]) |
| Overall study start date | 10/02/2006 |
| Completion date | 25/04/2008 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 90 |
| 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 rheumatoid arthritis 3. No exposure to anti-TNFa drugs in the last 3 months 4. Fulfil the National Institute for Clinical Excellence guidelines on the use of anti-TNFa drugs in rheumatoid arthritis* and be: 4.1. About to start etanercept or adalimumab (treatment group) 4.2. About to start methotrexate (control group) * The patients in the control group must have had adequate therapeutic trial of at least one previous Disease Modifying Anti-Rheumatic Drug (DMARD) rather than two |
| Key exclusion criteria | 1. Previous cardiovascular or cerebrovascular event 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 hypercholesterolaemia on stable medication for the last 3 months |
| Date of first enrolment | 10/02/2006 |
| Date of final enrolment | 25/04/2008 |
Locations
Countries of recruitment
- Scotland
- United Kingdom
Study participating centre
Vascular and Inflammatory Diseases Research Unit
Dundee
DD1 9SY
United Kingdom
DD1 9SY
United Kingdom
Sponsor information
University of Dundee (UK)
University/education
University/education
Research and Innovation Services
Dundee
DD1 4HN
Scotland
United Kingdom
| Phone | +44 (0)1382 344664 |
|---|---|
| j.z.houston@dundee.ac.uk | |
| Website | http://www.dundee.ac.uk |
"ROR" |
https://ror.org/03h2bxq36 |
Funders
Funder type
Industry
Wyeth
Private sector organisation / For-profit companies (industry)
Private sector organisation / For-profit companies (industry)
- Location
- United States of America
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/03/2010 | Yes | No |
