Atorvastatin and endothelial function in systemic lupus erythematosus (SLE) patients

ISRCTN	ISRCTN19073445
DOI	https://doi.org/10.1186/ISRCTN19073445
Protocol serial number	FAPESP Grant No.: 2003/06738-0
Sponsor	State of São Paulo Research Foundation (FAPESP) (Brazil)
Funders	Federal University of Minas Gerais (Brazil) - Rheumatology Division; Board of Education, Research and Extension (DEPE) (ref: 078/03), Federal University of São Paulo-Escola Paulista de Medicina (Brazil) - Rheumatology Division

Submission date: 12/06/2009
Registration date: 21/07/2009
Last edited: 21/07/2009

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

Dr Gilda Ferreira
Scientific

Pasteur Avenue, 135/1403
Belo Horizonte
30150-290
Brazil

Phone	+55 031 9617 4211
Email	gildap@terra.com.br

Study information

Primary study design	Interventional
Study design	Interventional single-centre non-randomised unblinded temporal series study with a parallel control group
Secondary study design	Non randomised controlled trial
Study type	Participant information sheet
Scientific title	Evaluation of the atorvastatin effect on endothelial-dependent vasodilation in patients with systemic lupus erythematosus: an 8-week controlled trial
Study objectives	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(s)	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)
Health condition(s) or problem(s) studied	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 / device / biological / vaccine name(s)	Atorvastatin
Primary outcome measure(s)	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.
Key secondary outcome measure(s)	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.
Completion date	23/02/2006

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Female
Target sample size at registration	88
Key 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
Key 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
Date of first enrolment	21/07/2004
Date of final enrolment	23/02/2006

Locations

Countries of recruitment

Brazil

Study participating centre

Pasteur Avenue, 135/1403

Belo Horizonte
30150-290
Brazil

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?
Results article	results	01/10/2007		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes