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

ISRCTN ISRCTN19073445
DOI https://doi.org/10.1186/ISRCTN19073445
Secondary identifying numbers FAPESP Grant No.: 2003/06738-0
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

Study designInterventional single-centre non-randomised unblinded temporal series study with a parallel control group
Primary study designInterventional
Secondary study designNon randomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet
Scientific titleEvaluation of the atorvastatin effect on endothelial-dependent vasodilation in patients with systemic lupus erythematosus: an 8-week controlled trial
Study objectives1. 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) studiedSystemic lupus erythematosus (SLE)
InterventionPatients 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 typeDrug
Pharmaceutical study type(s)
PhasePhase IV
Drug / device / biological / vaccine name(s)Atorvastatin
Primary outcome measure1. 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 measures1. 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 study start date21/07/2004
Completion date23/02/2006

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexFemale
Target number of participants88 patients with SLE
Key inclusion criteria1. 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 criteria1. 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 enrolment21/07/2004
Date of final enrolment23/02/2006

Locations

Countries of recruitment

  • Brazil

Study participating centre

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

Sponsor information

State of São Paulo Research Foundation (FAPESP) (Brazil)
Research organisation

R. Pio XI, 1500 - Alto da Lapa
São Paulo
05468-901
Brazil

Phone +55 11 3838 4000
Email converse2@fapesp.br
Website http://www.fapesp.br
ROR logo "ROR" https://ror.org/02ddkpn78

Funders

Funder type

University/education

Federal University of Minas Gerais (Brazil) - Rheumatology Division; Board of Education, Research and Extension (DEPE) (ref: 078/03)

No information available

Federal University of São Paulo-Escola Paulista de Medicina (Brazil) - Rheumatology Division

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot 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