Contact information
Type
Scientific
Primary contact
Dr Gilda Ferreira
ORCID ID
Contact details
Pasteur Avenue
135/1403
Belo Horizonte
30150-290
Brazil
+55 031 9617 4211
gildap@terra.com.br
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
FAPESP Grant No.: 2003/06738-0
Study information
Scientific title
Evaluation of the atorvastatin effect on endothelial-dependent vasodilation in patients with systemic lupus erythematosus: an 8-week controlled trial
Acronym
Study hypothesis
1. That atorvastatin therapy improves endothelium-dependent arterial dilation in systemic lupus erythematosus (SLE) patients with and without conventional risk factors for atherosclerotic disease
2. That atorvastatin therapy reduces the plasma levels of non-traditional laboratory markers for atherosclerosis in SLE patients
Ethics approval
Local Medical Ethics Committee (Comitê de Ética em Pesquisa da Universidade Federal de Minas Gerais) approved on the 5th November 2003 (ref: ETIC 285/03)
Study design
Interventional single-centre non-randomised unblinded temporal series study with a parallel control group
Primary study design
Interventional
Secondary study design
Non randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Systemic lupus erythematosus (SLE)
Intervention
Patients were divided in two groups:
1. The intervention group consisted of 64 patients who received atorvastatin 20 mg/day during 8 weeks. Thirty-three patients in the intervention group had hypertension, dyslipidaemia and/or obesity, while the remaining 31 did not have any conventional risk factors for CHD.
2. The control group comprised 24 SLE patients followed in the same period without atorvastatin (no treatment)
To reinforce and check adherence to the protocol, phone calls or personal contacts were performed 30 days after the beginning the study and atorvastatin tablets were counted at the end of the study. At baseline and at the end of the 8-week period, all 88 participants underwent complete clinical examination, brachial artery ultrasound and blood sampling for laboratory analysis.
Total duration of treatment: 8 weeks
Total duration of follow-up: 8 weeks
Definitions:
1. Family history of CHD: presence of clinical CHD or sudden death in first-degree relatives at ages before 55 years old and 65 years old for men and women, respectively
2. Hypertension: blood pressure higher than 140 mmHg/90 mmHg or current use of antihypertensive medications
3. Obesity: body mass index (BMI) over 30 kg/m^2 and/or presence of abdominal obesity, considered as abdominal circumference above 88 cm
4. Diabetes mellitus: fasting plasma glucose higher than 126 mg/dl or use of oral hypoglycaemic agents or insulin
5. Dyslipidaemia: high density lipoprotein (HDL) cholesterol serum levels less than 40 mg/dl or low density lipoproteins (LDL) cholesterol serum levels greater than 130 mg/dl or total cholesterol serum levels greater than 200 mg/dl or triglyceride serum levels greater than 200 mg/dl
6. Menopause: amenorrhoea for more than one year or use of hormonal replacement therapy
SLE disease activity and damage were measured using SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) and SLICC (The Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index for Systemic Lupus Erythematosus), respectively.
Intervention type
Drug
Phase
Phase IV
Drug names
Atorvastatin
Primary outcome measures
1. Resting diameter (mm)
2. Resting flow (ml/min)
3. Hyperaemia flow (mL/min)
4. Flow-mediated dilation (%)
5. Glyceryl-trinitrate induced dilation (%)
Measured at baseline and 8 weeks.
Vascular studies were performed at room temperature (25 - 28°C) using high-resolution ultrasound equipment, vascular colour echo-Doppler with flow mapping (ACUSON, Mountain View - California, USA) and multiple-frequency linear 7 MHz transducer. All patients were evaluated between 8:00 and 10:00 am after 12 hours overnight fast. Antihypertensive medication was stopped 24 hours before the study. All exams were performed by the same examiner and with the guidelines for ultrasound assessment of endothelial-dependent flow-mediated dilation of the brachial artery. Recorded images were later analysed by the examiner without any information on the patient's identification.
Secondary outcome measures
1. Total cholesterol (mg/dl)
2. LDL-cholesterol (mg/dl)
3. HDL-cholesterol (mg/dl)
4. Triglycerides (mg/dl)
5. Creatine phosphokinase (CPK)
6. Homocysteine (µmol/L)
7. Lipoprotein-a (mg/dL)
8. Endothelin-1 (pg/ml)
9. Cytokines and receptors (tumour necrosis factor-alpha, sTNFR1 and sTNFR2)
10. Chemokines (CL2, CCL3 and CXCL9) serum levels
11. Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score
12. Anti-DNA antibodies (0 = absent, 1 = present)
13. Anti-oxidised LDL antibodies (0 = absent, 1 = present) and anti-lipoprotein lipase antibodies(0 = absent, 1 = present)
14. Anticardiolipin antibodies (GPL or MPL)
Measured at baseline and 8 weeks.
Laboratory exams were performed according to standard routine techniques. Anti-dsDNA antibodies were detected by indirect immunofluorescence in Crithidia luciliae. Homocysteine and lipoprotein-a serum levels were measured by liquid chromatography (reference range less than 15 µmol/L) and immunonephelometry (Dade Behring, reference range less than 30 mg/dl), respectively. The concentration of cytokines, chemokines, endotelin-1, anti-DNA antibodies, anti-oxidised LDL antibodies, and anti-lipoprotein lipase antibodies, anticardiolipin antibodies were determined by enzyme immunoassay. Anticardiolipin antibodies were considered positive when higher than 20 GPL or 11 MPL.
Overall trial start date
21/07/2004
Overall trial end date
23/02/2006
Reason abandoned
Eligibility
Participant inclusion criteria
1. Female
2. SLE according to the American College of Rheumatology revised classification criteria
3. Disease diagnosis equal or greater than 1 year
4. Aged above 18 years old
5. Regular menstruation
Participant type
Patient
Age group
Adult
Gender
Female
Target number of participants
88 patients with SLE
Participant exclusion criteria
1. Current or past use of hypolipidemic drugs in the last six months
2. Menopausal women
3. Diabetes mellitus
4. Serum creatinine above 1.2 mg/dl
5. Pregnancy
6. Smoking status (last 12 months)
7. Family history of coronary heart disease (CHD)
8. Skeletal myopathic disease and/or elevated creatinine phosphokinase
9. Hepatic disease
10. Ciclosporin use
Recruitment start date
21/07/2004
Recruitment end date
23/02/2006
Locations
Countries of recruitment
Brazil
Trial participating centre
Pasteur Avenue, 135/1403
Belo Horizonte
30150-290
Brazil
Sponsor information
Organisation
State of São Paulo Research Foundation (FAPESP) (Brazil)
Sponsor details
R. Pio XI
1500 - Alto da Lapa
São Paulo
05468-901
Brazil
+55 11 3838 4000
converse2@fapesp.br
Sponsor type
Research organisation
Website
Funders
Funder type
University/education
Funder name
Federal University of Minas Gerais (Brazil) - Rheumatology Division; Board of Education, Research and Extension (DEPE) (ref: 078/03)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Federal University of São Paulo-Escola Paulista de Medicina (Brazil) - Rheumatology Division
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
2007 results in http://www.ncbi.nlm.nih.gov/pubmed/17693444
Publication citations
-
Results
Ferreira GA, Navarro TP, Telles RW, Andrade LE, Sato EI, Atorvastatin therapy improves endothelial-dependent vasodilation in patients with systemic lupus erythematosus: an 8 weeks controlled trial., Rheumatology (Oxford), 2007, 46, 10, 1560-1565, doi: 10.1093/rheumatology/kem186.