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
ETADA90 v1
Study information
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
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 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
Tayside Committee on Medical Research Ethics. Date of approval: 05/09/2005 (ref: 05/S1401/112)
Study design
Observational open-label single-centre study
Primary study design
Observational
Secondary study design
Cohort study
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
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
Phase
Not Specified
Drug names
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 trial start date
10/02/2006
Overall trial end date
25/04/2008
Reason abandoned (if study stopped)
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 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
90
Participant 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
Recruitment start date
10/02/2006
Recruitment end date
25/04/2008
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
Funders
Funder type
Industry
Funder name
Wyeth
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
For-profit companies (industry)
Location
United States of America
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
Basic results (scientific)
Publication list
2010 results in: http://www.ncbi.nlm.nih.gov/pubmed/20080919